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Laboratory Diagnosis and Inflammation Monitoring in Rheumatology
Ph.D. Khanov, A.G.

The doctrine of inflammation is the cornerstone of medical science (clinical pathology). While healing, the physician gradually passes from the symptoms or external manifestations of the disease to the essence of the processes that are taking place. The external manifestations of the disease include also the laboratory tests, and the results of additional methods of examination. But even the most modern diagnostic methods do not bring us much closer to understanding the pathogenesis or driving forces of the disease. The real clinical practice comes down to the formulation of the “correct diagnosis”, corresponding to the ICD classifier. And the processes that generate a wide range of diseases of a certain class recede into the background. Speaking of the disease, the clinician describes it through the eyes of a pathomorphologist. To change the situation, attempts were made at the end of the last century, namely, to single out an independent discipline – clinical pathology, as a universal one for various clinical disciplines, from therapeutic to surgical, where attention is not paid to specific diseases, but to the internal mechanisms which generate them. At present, a doctor, accumulating experience, keeps in mind, more and more diagnoses and symptoms, and constantly moving from general to private and then back, through logical operations, even without seeming to think about the patient or doing some other job, suddenly comes to “illumination” – the “right” diagnosis.

In reality, medicine is neither science nor art, but it is increasingly being transformed into a specific kind of service where certain rules and economic laws operate. So under these circumstances it is impossible to do without classification of diseases. All classifications are based on clinical and morphological forms, where already recorded events are fixed, and not the mechanisms that led to it.
Attempts were made to apply the biological principles of taxonomy to the classification of diseases in order to take into account the processes of their generators. But we must really understand that to become viable any classification must be tied to realities of our life (including economical ones). It is enough  to recall examples from other areas of our life, when, despite enormous intellectual and material costs, large-scale projects failed (“non-sticking” tires, inhaled insulin or 3G mobile phone, ahead of the reality of life for 10 years). The authors of the biological classification proposed the classification of inflammation on the example of pneumonia:

Kingdom – diseases
Group – Inflammatory
Family – Purulent
Genus (nosological form) – Pneumonia
Type (clinical form) – Staphylococcal
Variety (variant of the clinical form) – left, right, share, segmental, abscessing, septic.

This classification is very interesting and promising methodically, but within the existing system of medical care it is unlikely to realize. But, for individual clinicians it is possible to find out not only a clinical diagnosis, but also a pathogenetic diagnosis of the process. Pathogenetic diagnosis should include a process characteristic, its activity, phase, the tendency to destruction or various types of regeneration. In fact, the work of a rheumatologist is a cure of inflammation of various forms and manifestations. And we should bear in mind that rheumatic diseases are namely inflammations of the connective tissue in total. Inflammation is a typical pathological process that occurs under the influence of various factors (exogenous, endogenous), characterized by a standard set of vascular-tissue changes, regardless of the localization of the process and the nature of the etiologic factor. Researchers distinguish banal (nonspecific) inflammation and specific (caused by special pathogens – tuberculosis, syphilis, leprosy, etc.) ones. Morphological forms of these species fit into the alternative (characterized by the predominance of dystrophic-necrobiotic changes in organs and tissues), exudative (characterized by the predominance of exudate formation over the processes of alteration and proliferation), productive inflammation (characterized by proliferation of cell elements), including granulomatous. Clinically, this is manifested through exudative-destructive (EDI) inflammation. In its development, EDI passes three main phases: preparation, infiltration, repair, and reduces to activation of leukocytes, primarily neutrophils. Leukocyte mediators of inflammation are various and through them the connection of the inflammatory focus is established with the whole organism. Mediators of inflammation induce the synthesis of proteins in the liver, which are combined under the name “acute phase proteins”. The first of the BOPs was the C-reactive protein (CRP), then the serum amyloid protein A (SAP-A), α1-antitrypsin, haptoglobulin. Active neutrophils produce inflammatory cytokines IL-1, TNF, IL-6, IL-17.

In a number of cases, the EDI is chronized. A classic example of this is a disease – “systemic granulomatosis”, which begins in adolescence with multiple furunculosis of the skin and can result in pararectal abscesses, osteomyelitis or other severe purulent foci.
Another form of inflammation is immune inflammation, realized by the state of humoral and cellular immunity. Proliferation of clones of T-lymphocytes takes place on the one hand, and B-lymphocytes produce antibodies on the other hand. The nature of the pathological process is determined by the cells the antibodies are targeted at. The population of antibodies is incredibly heterogeneous. The immunoglobulins circulating in blood are divided into 5 classes.
The theory of the inflammation nature is very important in practical treatment. The rheumatologic patient is comorbid and in real life he gets into various medical situations: colds, bronchitis, pneumonia, kidney and other infections. And here it is important to understand if it is the activity of rheumatic disease or intercurrent infection and make the right choice of treatment tactics.
The current state of affairs requires a radical improvement in the laboratory diagnosis of inflammation. The existing methods of laboratory diagnosis do not always adequately reflect the situation in the focus of inflammation.
Traditionally, to assess the activity of inflammation, the number of leukocytes and the leukocyte formula (neutrophilia with a left shift) are calculated. But the results of counting leukocytes can mislead the doctor. Destruction processes may really occur in the focus of inflammation, and the number of leukocytes in the blood does not increase, or even decreases. In this case, leukopenia can be either true or false. This is especially revealed in septic states due to intoxication or sticking of leukocytes to the walls of postcapillary venules.
The level of ESR does not fully reflect the state of inflammation either, as it depends on the number and properties of red blood cells. But because of its simplicity, this test is still widely used even in modern clinics. The definition of ESR cannot be compared to any other laboratory method by its simplicity. It should be pointed out that ESR cannot serve to assess the effectiveness of treatment of the inflammatory process due to the fact that the rate of ESR, once raised, can remain high for a long time (trace reaction).
The way out is seen in the complex definition of proteins of the acute phase of inflammation, which must be correlated with clinical and other laboratory indicators. The acute phase response includes fever, leukocytosis, hyperproduction of glucocorticoids and catecholamines (adaptive hormones). At the same time, some of the acute phase proteins do not increase in the blood with inflammation, but on the contrary they decrease due to leaving into the extracellular space. They are also called negative BOP-albumin (negative nitrogen balance), α and β-lipoproteins (lipolysis), trasferrin.

In addition, in cases of severe inflammation with intoxication and liver damage, the synthesis of proteins in liver is reduced. This leads to the fact that the level of BFR is low and does not correspond to the degree of inflammation. In order to bypass the diagnostic “trap”, it is necessary to determine not only the BF in blood, but also cytokines that trigger the formation of BF in the liver.
In the laboratory there are diagnosticums for various BOP (C1-2-3-4-5, kallikrein, kininogen, plasminogen, CRP, ceruloplasmin, acid glycoprotein, antitrepsin, macroglobulin, haptoglobin, serum amyloid protein). BOPs are formed in liver under the influence of inflammatory cytokines. Adaptive hormones (HA and CA) are involved in the induction of BFW synthesis. In most cases, hormones prepare and cytokines trigger the synthesis. But macroglobulins are formed only under the influence of hormones. The sensitivity of the results of the BOP is different. The most sensitive BOP is serum amyloid protein, then come CRP, chymotrypsin, ceruloplasmin, acid glycoprotein (orosomucoid). The results of the determination of antitrypsin for the diagnosis of inflammation are not informative due to the frequent congenital insufficiency of this protein. The results of haptoglobin or fibrinogen tests are not very informative, because they are consumed during clotting, hemolysis, or are withdrawn from recirculation through RES.  False positive results of sensitive BOP are possible too. So, SAP-A is included as a protein component in high-density lipoproteins. Therefore, its titers will depend on the lipid composition of the blood. CRP is the most popular of all BOPs, especially when being determined “on-line”. α1-antichymotrypsin is convenient for a single determination, because of its narrow norm limits and the possibility to determine it by different methods.

But with many forms of chronic inflammation, the BFR titers do not reflect the activity of the process. If the process is local (in the lungs, kidneys, brain, liver), it is important to assess the degree of destruction in the inflammation zone objectively. EDV may terminate rapidly, but it can last for a long time, passing into a chronic recurrent course. The driving force of EDV are neutrophils or polymorphonuclear leukocytes (PML). But the inflammation can be realized not only due to PML, but through mononuclear cells. In this case, the inflammatory process becomes chronic from the very beginning. In this case, mononuclear infiltrates are formed. They can be diffuse in various organs and different areas, and local, delimited from normal tissue in the form of granules. Diffuse infiltrates are most often formed in the case of viral infections (for example, in hepatitis B). Granuloma is the focus of productive inflammation in the form of a perivascular cluster of mononuclear cells that are at different stages of maturation and activation. There are many different types of granulomas: actinomycotic, anular, beryllium, brucellosis, typhoid, giant cell, dental, granuloma of foreign body, intubation, infectious, injecting, candidoid, cystic, lepromatous, lipoid, liponecrotic, lipofagic, listeriosis, macrophagal, odontogenic subcutaneous, periapical , radical, rheumatic, sapna, sarcoid, silicotic, syphilitic, sclerotic, spermatogenic, spermatozoa, typhus, tylkoz, tubercular, tuberculoid, tularemic, venereal, mushroom, fat, malignant, ring-shaped). Also, granulomas are separated by anatomical localization (face, nose, etc.). In the process of existence, the granuloma can remain compact, but can also pass into diffuse infiltrates as in sarcoidosis, deep mycoses, hypersensitive pneumonitis and in other cases. Both local and diffuse granulomas disrupt the function of the organ where they develop. And diffuse ones do it in a greater degree.
According to the established traditions of pathomorphologists, both focal and diffuse inflammation with mononuclear cells are called “productive” or “proliferative”. But, in fact, there is no proliferation (multiplication) of cells in the infiltrate. Inflammatory cells are brought to the inflammatory focus by blood and lymph. The overwhelming majority of these cells are not divided in the focus and it is preferably to use the term “mononuclear inflammation” (MB).

There are different classifications of granulomas. Depending on the etiology, infectious, non-infectious and idiopathic granulomas are distinguished. Infectious granulomas occur during bacteria, fungi, protozoa or helminths infections. Bacteria that cause granulomas are usually located intracellularly, parasitizing in macrophages. Such granulomas occur with tuberculosis, leprosy, brucellosis, toxoplasmosis, typhoid fever, syphilis and other bacterial infections.
Fungal infection also develops granulomas with the development of deep mycoses. Fungi are found in tissues in the form of filamentous structures (candidiasis, aspergillosis), druses (actinomycosis) or rounded spherical bodies (blastomycosis, sporotrichosis, histoplasmosis). The process is localized in the deep layers of the skin and lungs, but can affect the liver, spleen, lymph nodes and other organs. Farm workers also have granulomas associated with fungi – a “farmer’s lung” by inhalation particles of rotten hay or grain; “Furrier lung” – when inhaling animal wool particles; ” poultryman lung” – the birds’ parts? “Bagasse” – by inhaling particles of moldy sugar cane; “Lung of New Guinea dwellar” – particles of rotten straw, covering the roofs of Aboriginal wigwams.

When infecting protozoa (Protozoa) granulomas (leishmaniasis or trypanosomiasis) can develop after a bite on the lips of the “kiss bug”, which brings Trypanosoma cruzi in the wound. Multiple granulomas can develop with helminthiases (schistosomiasis – when inserted into the tissue of Shistosoma mansoni,  the class of trematodes or flukes). Granulomas are formed in skeletal muscles when inserting Trichinella larvae or filarias into deep layers of skin, lungs and other internal organs.
Noninfectious granulomas are formed in lungs by inhalation of  SiO2 particles (silicosis), metal or asbestos dust and Bellirium salts.
Idiopathic granulomas include granulomas in cases of sarcoidosis, Crohn’s disease, Wegener’s syndrome, Lefler’s syndrome and idiopathic eosinophilic pneumonia.
Granulomas can be divided according to the cellular composition. In macrophage granulomas, the cellular composition is practically represented by macrophages only. There are lymphocytic granulomas. There are granulomas, where many giant multinucleated cells and / or eosinophils and mast cells present, especially with helminthiases and deep mycoses. We must not forget that granuloma is not static, but mobile formation, in which the cellular composition is constantly changing and the macrophage granuloma can turn into a giant cell, epithelioid or other form.

In the development of any granuloma, the phases of initiation, active development (growth) and wilt are identified.
Granulomas occur in two ways. The first path is associated with irritation of the macrophages of the organ where the occurrence of granulomatosis is planned. Tissue macrophages can be fixed and wandering. Both are formed from blood monocytes. Both microbes and non-metabolizable non-infectious particles can serve as stimuli. The “irritated” macrophage begins to produce inflammatory cytokines that activate the nearby endothelium. Activated endothelium begins to produce adhesive proteins that catch monocytes from the flowing blood. A primary accumulation of monocytes is formed around the vessel, which turn into macrophages of the future granuloma, which also produce cytokines of the IL-8 type, attracting PML into the infiltrate with the development of destruction, which further stimulates the resident macrophages, potentiating the growth of the granuloma.

In the second variant of granuloma development, the stimulus to the development of granuloma comes from T-cells – T-lymphocytes – delayed type hypersensitivity (GZT). Granulomas of this type develop only in the body with an allergy to the inducer granulomas. T-lymphocytes on contact with the antigen begin to produce cytokines and, first of all, IL-2. Under the influence of IL-2 macrophages and endothelium are transformed into cells representing a specific antigen. This leads to the fact that the presentation of the antigen occurs in certain (local) places. But in viral infections, the presentation of virus antigens is more extensive, which causes the formation of diffuse mononuclear infiltrates. The role of B – lymphocytes in the formation of granulomas is to develop antibodies that make a complex with the antigen. The resulting immune complex additionally irritates macrophages, which potentiates granulomatosis.
In the active granuloma phase, macrophages and lymphocytes enter the focus. Macrophages produce IL-1 and other cytokines that stimulate lymphocytes. Lymphocytes produce IL-2 and other cytokines that stimulate macrophages. Macrophages are involved in the inflammatory process of PML, eosinophils, corpulent cells. The appearance of PML in the inflammatory focus leads to the disintegration of the tissue and the formation of caseous granuloma.

Granulomas, like other forms of mononuclear inflammation have a chronic course. This is due to the lifespan of macrophages, which is significantly longer than neutrophils. Macrophages can stimulate themselves through the actually produced cytokines (TNF-α). Persistent inflammatory inducers in macrophages (parasites, mycobacteria, nonmetabolizable particles) that cause macrophages to produce new mediators of inflammation. But the main mediators of macrophage inflammation are not destruction factors, but cytokines such as IL-1 and TNF-α that support infiltration. The stability of granuloma is attached to the association of macrophages with T-lymphocytes and endothelium. The activity of neutrophils and the destruction they cause attract new mononuclear cells to the focus.

A classic example of such inflammation is rheumatoid arthritis. In RA, immune complexes are formed, consisting of anti-IgG antibodies (rheumatoid factor) and altered IgG. These complexes are deposited in the synovial membrane of the joint. They irritate neutrophils and macrophages, which secrete collagenases that destroy the joint tissue. In response, the granulation tissue grows and a pannus (a film of synovia cells) is formed. Pannus cells cover the cartilage and destroy it. Destruction generates an influx of new inflammatory cells into the source, the process proceeds “in a circle”, progresses and leads to complete destruction of the joint.

The granuloma is a “smoldering” focus, which can suddenly become more active. Exacerbation may occur as a result of a specific attack upon contact with a specific antigen (eg animal hair, feathers of birds) or under the influence of universal nonspecific factors, through endotoxin in contact with microbes, tissue decay products, etc. On the one hand the pathophysiological significance of granuloma is that it disrupts the normal functioning of the organ where it develops, and on the other hand it fences off the body from microbes and other foreign particles that can disrupt homeostasis as a whole.

Granuloma in its development reaches a certain size, and then its growth stops in contrast to a tumor that does not have the upper limit of growth. The wilting phase of the granuloma is subject to certain processes. Starting from a certain moment, a balance is established between the inflow and outflow of cells. This depends on the properties of the endothelium in which the adhesiveness decreases, which reduces the influx of cells into the granuloma. At the same time, the outflow of cells through blood and lymph begins to predominate. With a favorable outcome, the granuloma can completely resolve. Simultaneously, as they grow, the cells that produce prostaglandins E accumulate in the granuloma, which reduce the activity of T-lymphocytes and macrophages. IL-1, IL-6 and other cytokines formed by granuloma cells include the synthesis of glucocorticoids through the hypotolamo-pituitary-adrenal axis. Most often the granuloma is subjected to fibrotic transformation, especially in those granulomas where the destruction takes place. Fibrogenesis is associated with macrophages, which produce not only inflammatory mediators, but also growth cytokines that stimulate fibrogenesis, which restrains inflammatory infiltration. The granuloma withers and is completely replaced by a fibrous tissue in the final.
Biopsy is a “gold standard” for diagnosing granulomas. But, the morphological picture of the granuloma only ascertains the process, but does not specify its activity and development tendency. The order of the Ministry of Health of the Russian Federation (2000) approved the nomenclature of clinical laboratory studies on proteins of the acute phase in blood serum, which includes:
4.1.10. Proteins of acute phase in serum: – C-reactive protein (CRP) – serum amyloid A protein – acidic alpha-1-glycoprotein (orosomucoid) – alpha-1-antitrypsin-ceruloplasmin – Haptoglobin – fibrinogen in the blood plasma – complement proteins – prealbumin

Summary Table for practical application of laboratory diagnostics of proteins of the acute phase of inflammation

Type of protein Function guideline standard Interpretation of results note
Complement system (consists of 9 consistently activated components and 3 inhibitors)
  There are two main ways (mechanisms) to activate the complement – classic and alternative. The classical pathway of complement activation is initiated by the interaction of the complement component C1q with immune complexes (antibodies associated with surface antigens of the bacterial cell). The result is its cytolysis. This mechanism combines the acquired immune system (antibodies) with the innate immune system (compliment). The alternative pathway of complement activation is initiated by interaction of C3b complement component with bacterial cell surface. Activation occurs without the participation of antibodies. This method of activation of complement refers to the factors of innate immunity Diagnosis and monitoring of immunocomplex disorders: SLE, vasculitis, glomerulonephritis, cryoglobulinemia, autoimmune hemolytic anemia. Activation of the alternative pathway is observed in allergic granulomatous angiitis, suspected congenital complement defect in recurrent infections and angioedema   Simultaneous determination of 3 parameters-C3, C4 components and the title of complementary activity allows you to assess the status of both classical and alternative activation pathways. Consumption of complement by the classical way (immune complexes) is accompanied by a decrease in all three indicators. When complement activation via the alternative pathway (e.g., glomerulonephritis) 3 and the titer of complement therapy activity is reduced, and C4 (a component of the classical cascade) is normal. Determination of complementary activity titers is a good method of screening for complement deficiency (characterizes the presence of all components of the complement activation pathway). Reduced or an undetectable level of the titer of complement therapy activity is indicative of hereditary deficiency of the complement system.  
Note: in clinical practice, the most widely used definition of the content of C3 and C4 components and the titer of complementary activity
The titer of complement therapy activity C3-component of complement     adults 50-140 U / ml.  in adults 0,50-1,2 g /l.   blood serum  blood serum
The C4 component of complement     in adults 0.2-0.5 g/l   blood serum
Kallikrein-kinin system
The kallikrein-kinin involved in the development of non-immune and immune inflammation and the microcirculation disorders, as functional and structural relationships is in connection with the coagulation and fibrinolytic systems within a single system of Hageman factor. Kallikrein is one of the main enzymes that make up the kinins and modulates the activity common to these systems is Hageman factor. This system consists of kinins, kininases and kininogenase enzymes. Their imbalance can lead to pathology. There is a hereditary predisposition to this imbalance.
Kallikrein One of the enzymes that are present in the blood and other body fluids that affect a number of plasma globulins, resulting in the formation of kallidin and bradykinin. Not used in medical practice
Plasminogen and tissue plasminogen activator (TPA’)
Plasminogen Plasma deficiency is an extremely rare event, more often there is a deficiency of tissue plasminogen activator (TPA). The deficit of TAP is one of the potential risk factors of thrombosis, although clinically it is not always the case. Tissue plasminogen activator (TPA) is released into the bloodstream from the endothelial cells of the vascular wall under stress, in particular in the cuff test (dosed vein compression). First, establish a baseline TAP, then 10-15 minutes on the forearm applied a tourniquet or inflate the cuff, causing venous stasis, and then take the second portion of blood in which re-define TAP. Compare the results of both samples. TAP has high amidase activity, enabling effective use to determine the method of chromogenic substrates.TAP determination is carried out in patients with thrombophilia as part of the panel of tests to determine the cause of thrombophilia, especially when stress cuff samples. Raising TAP after myocardial infarction is considered as an unfavorable factor. Violation of TAP release after venous stasis is described in patients with thrombosis and kidney disease. Determination of plasminogen is used for the diagnosis of DIC and thrombophilia; detection of fibrinolysis disorders; control of treatment with fibrinolytic drugs for thrombosis, thromboembolism, heart attacks. The reference values of plasminogen: 71-101% INCREASE in the content of PLASMINOGEN and its ACTIVATORS: pancreatitis; pancreatic necrosis;metastasizing prostate cancer, ovarian cancer;melanoma metastases;operations on the lungs, prostate, pancreas; hypercatecholaminemia (stress, thyrotoxicosis, hypertensive crisis, introduction of adrenaline); pregnancy pathology; terminal and other conditions accompanied by the development of DIC syndrome;cirrhosis; liver failure (liver failure). antiplasmin and anti-activator functions).PLASMINOGEN DEFICIENCY, USUALLY DEFICIENCY OF TISSUE PLASMINOGEN ACTIVATOR:recurrent venous thrombosis;systemic vasculitis;sepsis;nephrotic syndrome.  
Tissue plasminogen activator (tPA)     2-8 ng / ml The tPA level was decreased in patients with thrombotic disorders (deep vein thrombosis, myocardial infarction, ischemic stroke), malignant neoplasms and sepsis.The increased level of TPA antigen in its normal activity indicates a reduced degradation of tPA, which is observed in various liver diseases and heparin therapy. tPA — abbr. med. tissue plasminogen activator
Ceruloplasmin late acute phase protein inflammation, the main transport form of copper in the blood. It is an alpha-2-glycoprotein synthesized in the liver and some blood cells, brain, lungs, contains 6-8 copper atoms anemia of unknown origin with a low level of serum iron, which is not amenable to treatment with iron preparations; low number of platelets, leukocytes of unidentified etiology; hepatic pathology in children with negative markers of viral hepatitis; neurological symptoms with violation of gait and movements; direct relatives of the patient with Wilson’s disease-Konovalov for early detection; violation of bone development-osteopathy; long-term parenteral nutrition men-0.16-0.45 g/l women of 0.15 to 0.60 g/l The reasons for the increase of ceruloplasmin in the blood:acute inflammatory diseases of any organ – in this case, acts as a non-specific indicator of the acute phase of inflammation; with glomerulonephritis, for example, increases by 1-2 g/l, but with simultaneous liver damage remains within the normacute myocardial infarction – an increase of 0.6-2.0 g/lmalignant tumors, especially leukaemiaacute hepatitis-the first months of the disease, then in the formation of liver failure-decreasescirrhosis, predominantly alcoholic etiologybiliary cirrhosis


hyperfunction of the ovaries


Reasons for the decline in ceruloplasmin in the blood

aceruloplasminemia-the primary congenital deficiency of ceruloplasmin leads to pronounced disorders of iron metabolism, the symptoms are similar to hemochromatosis, but the transport of copper is disturbed to a lesser extent

secondary ceruloplasmin deficiency occurs due to the following conditions and pathologies

- extreme diets

- long-term parenteral nutrition

— unjustified treatment with penicillamine

- nephrotic syndrome-loss of ceruloplasmin along with other urine proteins

- exudative enteropathy – loss of ceruloplasmin with fecal masses

— malnutrition and malabsorption – malabsorption of nutrients in intestines

— violation of the synthetic function of the liver, ceruloplasmin is simply not able to be synthesized

Menkes disease or ” curly hair disease — is an X-linked pathology in which copper is disturbed from the digestive tract into the bloodstream; copper is inaccessible and ceruloplasmin is not synthesized

Wilson-Konovalov disease-in the liver, there is no enzyme responsible for the inclusion of copper in ceruloplasmin, disturbed removal of copper from the body, is an autosomal recessive disease, the frequency of 1/30 000; symptoms manifested in 20-40 years; copper in significant amounts is deposited in the liver, brain, iris, kidneys.

The FACTORS influencing the result:Smoking – decrease of ceruloplasmin levelduring pregnancy a gradual increase in 2-3 times standardsoral contraceptives-increaselow levels of ceruloplasmin are typical for newborns and infants up to 1 year of age, so the analysis is not applicable for early diagnosis of Wilson-Konovalov disease
Alpha-1 antitrypsin (alpha-antitrypsin) Alpha-1 – acid glycoprotein (orosomucoid) – an indicator of inflammation (acute phase protein). Acidic A1-glycoprotein (orosomucoid) is a plasma protein, the richest in carbohydrates. The carbohydrate part is represented by several polysaccharide chains attached to the polypeptide chain. It has the ability to inhibit the activity of proteolytic enzymes, change platelet adhesion, inhibit immunoreactivity, bind many LS (propranolol) and some hormones (progesterone).Orosomucoid refers to acute phase proteins. Its synthesis is stimulated by lipopolysaccharides released from macrophages activated by interleukin – 6 (IL-6). The main indications for use: monitoring of inflammation in various diseases. AdultsContent mg/ 100 ml 55-140(0.55-1.4 g/l)Content of µmol / l 13.4 -39 Inflammation (infection, trauma, surgery) Recurrence of the tumor, especially tumors, with development of necrosis, such as squamous cell lung cancer, renal cell cancer, adenocarcinoma of the breast and colon, and simultaneously with haptoglobin from hemolysis in vitro, and treatment with corticosteroids. Differentiation of the reaction of the acute phase (increase) from the influence of estrogens (normal or reduced levels), because these processes increase ceruloplasmin, and 1-antitrypsin and many other reagents of the acute phase. Together with haptoglobin, and 1-acid glycoprotein may be the best object of study to evaluate hemolysis in vivo. The content of these two proteins is usually increased and decreased simultaneously;thus, an increased level of orosomucoid with normal haptoglobin indicates a reaction of the acute phase with moderate hemolysis in vivo. The content of orosomucoid in the blood increases with inflammatory processes (infections, rheumatic diseases, injuries, surgery), tumors. The study of this indicator in dynamics allows to evaluate the dynamics of the inflammatory process, and in tumors, in the case of their surgical treatment, to diagnose the occurrence of relapse.Since the concentration of orosomucoid in the blood increases during inflammatory processes, it is capable of binding an increased amount of LS taken by the patient, resulting in dissociation between the pharmacological effect and the concentration of the drug in the blood.The reduced concentration of orosomucoid in serum is possible in early childhood, during pregnancy (in the early stages), severe liver damage, nephrotic syndrome, estrogen intake, oral contraceptives. With age, the concentration of albumin in the blood and especially A1-glycoprotein decreases; since many LS (for example, lidocaine, propranolol, tricyclic antidepressants) bind to these proteins after entering the bloodstream, elderly people may increase the content of their free fraction, which creates prerequisites for the strengthening of pharmacodynamic action and the occurrence of side effects.Reduction of In infancy and early childhood. With the introduction of 17A – hydroxyandrost. Severe liver damage. The final stage of hepatocellular disease and in the absence of inflammation in nephrotic syndrome or other causes of protein loss.

Genetic factor.

In early pregnancy and the introduction of some contraceptives and medicines.

alpha 1-antichymotrypsin Protease inhibitor refers to the proteins of the acute phase of inflammation, synthesized in the liver. A glycoprotein of blood plasma. Deactivates enzymes that break down protein (elastase, trypsin and collagenase). Protease inhibitor (proteolytic enzymes) Belongs to the proteins of the acute phase of inflammation, produced in the liver. Refers to albumin. Provides 90-92% total antiprotease activity of blood plasma. It has a wide range of physiological and pharmacological effects. Suppresses the activity of enzymes: chymotrypsin, trypsin, plasmin, thrombin, elastase, kallikrein and collagenase. Its main physiological function is the inhibition of neutrophilic protease, elastase, which hydrolyzes structural proteins. Homozygous blood is increased by estrogen therapy, as well as acute inflammatory reaction. Diagnose severe infection, inflammation, tissue necrosis. Identification of patients at high risk of pulmonary emphysema. To verify congenital deficiency of alpha-1-antitrypsin 110-200 mg / DL (SI: 1.1-2 g/l)*significantly depends on the age Its concentration in serum or plasma increases with a variety of inflammatory processes: chronic, subacute and acute infectious diseases, the active form of liver cirrhosis and acute hepatitis, conditions after surgery, necrotic processes, the stage of early reconvalescence of thermal burns, chronic and acute pancreatitis. The concentration of alpha antitrypsin in the serum is significantly increased in malignant cancer: cancer (especially cervical) and metastases, lymphoma (especially Hodgkin’s disease). Quite often note erased forms of congenital antitrypsin deficiency. In children with this pathology, different forms of hepatopathies are found, in particular, early cholestasis. Cirrhosis can develop in 1-2% of patients. Clinically expressed congenital deficiency of alpha-1-antitrypsin is often combined with the basal form of juvenile emphysema and / or cystic fibrosis. Acquired forms of alpha-antitrypsin deficiency is possible with nephrotic syndrome, gastroenteropathy with protein loss, thermal burns in the acute phase.Decrease in the content of alpha-antitrypsin in blood serum can be diagnosed in patients with viral hepatitis as a violation of its formation in the liver. Increased consumption of this glycoprotein is observed in respiratory distress syndromes, coagulopathy, acute pancreatitis, which also causes a decrease in its concentration in blood serum. All patients with chronic liver disease recommended routine determination of alpha-antitrypsin, this is due to the inability to establish a correct and definitive diagnosis only on the basis of clinical data.  
Alpha-2-macroglobulin(AMG) Glycoprotein synthesized in the liver. Refers to albumin. causes 90-92% of the total antiprotease activity of plasma. Features a broad spectrum of action. Inhibits the activity of protease such as trypsin, chymotrypsin, thrombin, plasmin, kallikrein, elastase and collagenase. The main physiological function is to inhibit neutrophil elastase, protease, hydrolyzing structural proteins. If its activity is not controlled by alpha-1-antitrypsin, it begins to destroy lung tissue. Control of inflammation in acute and chronic inflammatory diseases, infections, as well as in some tumors. To diagnose the causes of emphysema, especially if the patient is not exposed to risk factors such as Smoking or regular contact with irritants such as dust and smoke.To identify the causes of prolonged jaundice and other liver disorders (mainly in children and adolescents). Examination of close relatives of the patient suffering from alpha-1-antitrypsin deficiency 2,5-4 g / l. Increases in inflammation and estrogen treatment.  Low concentrations of alpha-1-antitrypsin in the blood are accompanied by chronic pulmonary emphysema and infantile liver cirrhosis .  
Haptoglobin The haptoglobin (Haptoglobin) is acute-phase protein and a transport form for free hemoglobin.Synthesized in the liver. One of the types of globulins of blood.The main function of haptoglobin is to bind free hemoglobin (but not hemoglobin inside red blood cells), which is toxic to the body (especially the kidneys). Formed by the complex of haptoglobin-hemoglobin in 9 minutes is removed from the circulation by the liver where the hemoglobin breaks down into iron and globin, and haptoglobin returned to the bloodstream. The main component of alpha-2-globulin fraction of serum proteins. Due to the high molecular weight of this protein is mainly found only in plasma. Participates in the physiological regulation of blood coagulation, clot lysis and complement, as well as in the control of proteolytic effect collagenase leucocytes, lysosomal catepsin, pancreatic trypsin and chymotrypsin. It quickly inactivates proteases by blocking their proteolytic activity against proteins and other large peptides Synthesis of alpha-2-macroglobulin in places of growth of fibrous tissue in a liver allows to use it as a marker at cirrhosis and fibrosis of a liver. The concentration of CO2 in the blood is also determined in pancreatitis, peptic ulcer, diabetes, nephrotic syndrome, malignant neoplasms, pregnancy. Anemia;Suspected hemolysis;pre – and post-transfusion monitoring of the recipient;examination of patients with artificial heart valves.Hypertension of pregnant womenEstimation of acute phase parameters and disturbances in alpha 2 globulins on electrophoregramHypertension of pregnant women;

 evaluation of acute phase inflammation and disorders in the alpha-2 fraction of globulins on electrophoregram

Men-150-350 mg / 100 ml.Women-175-420 mg / 100 ml. 0 – 1 yearMen. 0 – 300 mg/mlW 0 – 235 mg/ml 

1 – 12 years

M 3-270 mg / ml

W 11 – 220 mg/ml


13 – 60 years

M 14 – 258 mg/ml

W 35 – 250 mg/ml


> 60 years


M 40 – 268 mg/ml

W 63 – 273 mg/ml

Rule increases In the treatment of estrogen;Pregnancies;Diabetes;Cirrhosis;Hepatitis (acute, chronic);Deficiency of alpha – 1 – antitrypsin;

Cerebral infarction;


In nephrotic syndrome, the levels are increased in proportion to the severity of protein loss and may exceed 600 mg / 100 ml.

Lowering standards

Lung disease;


Preeclampsia ;

Juvenile rheumatoid arthritis;

in extracorporeal circulation (e.g. open heart surgery) and in the terminal stage of critical conditions;

when lesions podjeludochnoi; myocardial infarction.

Improve standards for the treatment of estrogen;




Hepatitis (acute, chronic);

Deficiency of alpha – 1 – antitrypsin;

Cerebral infarction;


In nephrotic syndrome, the levels are increased in proportion to the severity of protein loss and may exceed 600 mg / 100 ml.

Lowering standards

Lung disease;


Preeclampsia ;

Juvenile rheumatoid arthritis;

in extracorporeal circulation (e.g. open heart surgery) and in the terminal stage of critical conditions;

in case of lesions of the pancreas; myocardial infarction.

Protein serum amyloid A (SAA) SAA is a normal serum protein (a precursor to fibrillar tissue AA protein) synthesized in the liver. SAA is a fast and highly responsive marker of the acute phase.Enhanced synthesis of SAA by hepatocytes in inflammatory diseases is stimulated by macrophage mediator-interleukin 1, which leads to a sharp increase IN SAA retention in the blood (by two or three orders compared to the norm). If the inflammatory process is completed, increased amounts of SAA are destroyed by macrophages. However, in the case of a long-existing inflammatory process, macrophages are not able to realize the complete degradation of SAA, and amyloid fibrils are assembled from its fragments. Amyloid is a glycoprotein, the main component of which are fibrillar proteins. There are four groups of these proteins, characteristic of certain forms of amyloidosis:

  1. AA-protein (non-associated immunoglobulins) generated from its analog protein SAA
  2. AL-protein (associated with immunoglobulins), its predecessor Are l-chains of immunoglobulins
  3. AF-protein, in the formation of which is mainly involved prealbumin
  4. ATTR-protein, the precursor of which is prealbumin

Amyloidosis — desprotegidos, accompanied by a profound disturbance of protein metabolism and the emergence of abnormal fibrillar protein in the interstitial tissue and the walls of blood vessels complex substances — amyloid.

The synthesis of SAA is triggered by the combined action of interleukin 1 and interleukin.

High concentrations of SAA in serum is a marker of AA-amyloidosis, which can be primary (recurrent disease, McCall and wells ‘ disease) and secondary. Secondary amyloidosis develops as a complication of a number of diseases: chronic infections (especially tuberculosis), diseases characterized by purulent-destructive processes (chronic non-specific lung diseases, osteomyelitis), malignant diseases (paraproteinemia, lymphogranuloma, cancer), rheumatic diseases (especially rheumatoid arthritis).In inflammatory processes, the concentration of SAA in serum can increase very significantly, especially when accompanied by secondary amyloidosis. less than 0.4 mg/l. Increase values:  

  1. acute phase reactions in infections, injuries, neuroses, surgery, sepsis;

2юcorticosteroid therapy.

  1. obstruction of the biliary tract;

4.nephrotic syndrome;

  1. the use of androgens;
  2. a malignant tumor, plasmacytoma;


8.hodgkin desiase;




The lower values:


  1. genetic deficiency of haptoglobin;
  2. hereditary spherocytosis;

3.hemolytic disease;

4.autoimmune hemolytic anemia;

  1. ineffective erythropoiesis;
  2. the use of estrogen;


8.neonatal period;

  1. pathology of the liver (cirrhosis).
C-reactive protein (CRP) C-reactive protein is a non-specific indicator of inflammation, which has a very high sensitivity to any tissue damage. It is synthesized by the liver as a response to inflammatory or necrotic processes in any part of the human body. A sharp increase in its concentration in the blood occurs during the first four hours of the disease. Thus, C-reactive protein in the blood is the first sign of the inflammatory process, reflecting the intensity. Diagnosis of acute infections;determination of the probability of cardiovascular complications in diabetes, atherosclerosis and in patients on hemodialysis;tumor diagnostics;evaluation of the effectiveness of treatment of chronic diseases;determination of the development of organ rejection after transplantation;evaluation of effectiveness of antibiotic therapy;determination of the extent of necrosis after myocardial infarction;

identification of complications in the period after surgery;

determination of reactivity of the process in diffuse connective tissue diseases and evaluation of the effectiveness of the treatment.

less than 5 mg / liter.  The norm for newborns is less than 1.6 mg / liter. With inflammation, its level can increase more than 20 times. This indicator is defined for diagnostic purposes and monitoring is necessary for disease monitoring.  
Prealbumin (transthyretin) Prealbumin (transthyretin) protein synthesized in the liver and metabolized primarily in the kidneys.   It is the predecessor of albumin. A transport protein that carries some hormones and vitamins (thyroxine – and retinol – vitamin a). The adequacy and sufficiency of protein and energy nutrition in patients on parenteral nutrition significantly and clinically significantly reflects. Transthyretin also is a sensitive acute phase protein of inflammation, but he appears as a “negative” acute-phase protein, i.e. the development of the inflammatory process, its content is reduced. Adults – 100 to 400 mg/L. Evaluation of parenteral nutritionEvaluation of the degree of inflammatory processes High content:Adrenal hyperactivity and the associated high levels of endogenous steroids;Parenteral administration of high doses of corticosteroids;Treatment with high doses of non-steroidal anti-inflammatory drugs;hodgkin.  

Lowering the content:


Insufficient protein in the diet;

Cirrhosis and other chronic liver diseases;

Some forms of hereditary amyloidosis, in which the antigen is localized transtiretina amyloid deposits in tissues. Clinical manifestation of hereditary forms of amyloidosis is a consequence of the substitution of one amino acid in the molecule, transthyretin.

If the content of prealbumin in patients on parenteral nutrition is significantly reduced, it is necessary to review the composition of nutrition.

Mutations in the prealbumin gene associated with the development of amyloidosis, which can have serious diagnostic value in determining some forms of hereditary amyloidosis.

Taking some medications can distort the results of the analysis. In particular, anabolic steroids, prednisolone and androgens increase performance, and estrogen, amiodarone and oral contraceptives lower them.

Cytokines and inflammation in rheumatological diseases

The immune system is in constant interaction of different levels from the central organs to the effector cells. The most diverse cells of the immune system can exchange information and carry out coordinated actions with the help of specific proteins of cytokines.
Note. (The term “Cytokines” was proposed by S. Cohen et al., 1974) Cytokines (cytokines) [Greek. kytos - a vessel, here - a cell and kineo - move, induce] – a large and diverse group of small-sized (molecular mass of 8 to 80 kDa) mediators of the protein nature – mediating molecules (“communication proteins”) involved in intercellular signaling mainly in the immune system.

Different types of cells through the cytokines act on other cells, stimulating or inhibiting their functions. More than a hundred different cytokines were found. Substances secreted by lymphocytes are called lymphokines, and substances released by lymphocytes and acting on all white blood cells are called interleukins, because they participate in the interaction of two types of leukocytes. The set and quantities of cytokines acting on the cell surface receptors – the “cytokine environment” – represent a matrix of interacting and frequently changing signals. Different tissues are characterized by their own healthy “cytokine environment.”

Cytokines include interferons, colony-stimulating factors (CSF), chemokines, transforming growth factors; tumor necrosis factor; Interleukins with historically established ordinal numbers and some other endogenous mediators. Interleukins having serial numbers starting at 1 do not belong to one subgroup of cytokines related by a common function. They can be divided into proinflammatory cytokines, growth and differentiating factors of lymphocytes, separate regulatory cytokines.

Classification of cytokines by mechanism of action

Today, about 200 individual polypeptide substances are classified into the cytokine system, which, according to their structural features and biological action, are divided into several self-contained groups. Grouping of cytokines by the mechanism of action allows them to be divided into the following groups:
• 1 group. Pro-inflammatory cytokines, providing mobilization of an inflammatory response;
• 2 group. Anti-inflammatory cytokines, limiting the development of inflammation;
• 3 group. Regulators of cellular and humoral immunity – natural or specific, possessing their own effector functions (antiviral, cytotoxic).
According to one of the accepted classifications, cytokines are:
•  Interferons, representing a large group of antiviral peptides (IF-b, IF-v, IF-g, IF-ni, IF-f);
• Colony-stimulating factors that activate the multiplication and differentiation of precursor cells of various hematopoiesis germs at various stages of their formation (G-CSF, M-CSF, GM-CSF);
• Chemokines, or chemotactic cytokines, which ensure the activation of migration of different types of leukocytes and some other cells (PF-4, MIP-2, MCP-1);
•  Transforming growth factors (PD-GF, TGF-in);
•  A group of tumor necrosis factors – TNF-α (TNF-β, TNF-α);
• Interleukins IL-1-29 (IL 1-29). ILs with numbers 1-29 cannot be combined into one subgroup of cytokines associated with a common function, and they can be divided into proinflammatory cytokines, growth and differentiating factors of lymphocytes, and separate circulatory cytokines
Retreat. Any inflammation is controlled by mediators and regulators of inflammation -interleukins. At present, there is a real opportunity to control the level of a wide range of interleukins. There are a large number of independent laboratories, and all new diagnostic kits are coming to the market, which do not require expensive equipment for their mastering. But in this situation there are a number of medical and social problems. A thinking clinician wants to control the inflammatory process as widely as possible and in dynamics. But it is rather difficult to explain the patient the necessity to spend $ 20 for one analysis that does not directly affect the course of treatment. Another problem lies in the mentality of the Russian patient. Nobody thinks that he will get sick “hard” and hopes to get by with medications from the “cheap” pharmacy. Education of the “position of the ostrich” is the result of sanitary education and TV-propaganda in public health issues, when they try to show individual “victories” over diseases and do not want to “upset” people with pictures of suffering and the social consequences of “serious” diseases.

Complex analysis of the level of serum cytokines and polymorphism of their genes (cytokine profile, polymorphism of cytokine genes, human immune constitution)
• The analysis includes the determination of 4 polymorphic variants of genes: IL-beta: interleukin 1-beta
• ILRA: a recipe antagonist of interleukin 1
• IL4: interleukin 4
• TNF-alpha: tumor necrotic factor alpha.

An analysis of the polymorphism of cytokine genes is a molecular genetic study that reveals the presence of the so-called pro-inflammatory variants of genes encoding the early stages of inflammation and the immune response. Carriers of such genes have an increased propensity to activate the immune system during surgical interventions, infections, mechanical effects on the tissue (ovum picking, embryo implantation with IVF). The presence of proinflammatory variants of IL (interleukin 1-beta), ILRA (interleukin 1 receptor antagonist), TNF-alpha (tumor necrotic factor alpha) predisposes to miscarriage.
Such patients develop complications of sepsis and other purulent-inflammatory diseases more often. When a pro-inflammatory variant of cytokine genes is detected, a special preparation plan for pregnancy or IVF is recommended.Interleukin 1 (Interleukin-1, IL-1)

Interleukin-1 beta (Interleukin-1b, IL-1β) is the predominant form of IL-1, which belongs to the group of pro-inflammatory cytokines. Under this name, two proteins (IL-1α, IL-1β) with a molecular weight of 17.5 kDa, secreted by phagocytic mononuclears of different tissue localization, are combined. The biological properties of IL-1α and IL-1β are very similar, or identical. IL-1α activates mainly T-lymphocytes, has autocrine and paracrine action, whereas IL-1β is a multifunctional cytokine with a wide spectrum of action, which plays a key role in the development and regulation of nonspecific defense and specific immunity. He is one of the first to be included in the response protective reaction of the organism under the action of pathogenic factors. It is synthesized and isolated mainly by macrophages and monocytes. Lymphocytes, fibroblasts can participate in its production. The target cells of this cytokine are immunocompetent, endothelial, epithelial cells, fibroblasts and others. It stimulates and regulates inflammatory and immune processes, activates neutrophils, T- and B-lymphocytes, stimulates the synthesis of acute phase proteins, increases phagocytosis, hemopoiesis, vascular wall permeability, cytotoxic and bactericidal activity, stimulates ACTH production. IL-1 is involved in the regulation of body temperature, its increased production leads to the development of fever. A strong increase in the level of IL-1 leads to hypotension, anorexia, destruction of cartilage in the joints, arterial hypotension.

Method of research CLIACLIA. Rules of preparation. General clinical and biochemical blood tests. General clinical and biochemical blood tests. Material for research. Transport environment.

Reference values, pg / ml Up to 5.0
Effect of medication
• Glucocorticoids, prostaglandins, cyclosporin A
Indications for prescription
Interleukin 1b – a cytokine, an indicator of the immune response in diseases, accompanied by inflammation
• Monitoring and evaluation of efficacy in antiviral, antibacterial or immunomodulatory therapy;
• in preterm infants – immunoreactive marker
Interpretation of results
Increasing the level

Decreasing the level
• Bacterial infections;
• autoimmune and inflammatory diseases;
• multiple trauma (also high levels of IL-2, IL-6 and, especially, tumor necrosis factor);
• rejection of the kidney transplant;
• threat of abortion;
• Acute and chronic myelogenous leukemia, hairy cell leukemia;
• DIC-Syndrome;
• UV radiation

Psoriasis, atopy, respiratory viral infections, lung cancer, effects on the body  of certain medicines

Interleukin-4 (IL-4, IL-4)
Interleukin-4 (IL-4), or B-cell growth factor is a protein with a molecular weight of about 20 kD. Refers to anti-inflammatory cytokines. It is mainly produced by a population of T-helper lymphocytes, as well as mast cells, macrophages and stromal cells. Has multiple effects on the immune system, in particular, together with other cytokines causes proliferation of B-lymphocytes, regulates the secretion of immunoglobulins. IL-4 stimulates the proliferation of resting T-lymphocytes and enhances their antitumor effect. It is a factor in the growth of mast cells. The main directions of the biological activity of IL-4: enhances eosinophilia, the accumulation of mast cells, the secretion of IgG4, Th2-mediated humoral immune response; includes the synthesis of IgE by activated B lymphocytes; has local antitumor activity, stimulating the population of cytotoxic T-lymphocytes and infiltration of the tumor with eosinophils; suppresses the release of inflammatory cytokines (α-TNF, IL-1, IL-8) and prostaglandins from activated monocytes, production of cytokines by Th1 lymphocytes (IL-2, g-IFN, etc.). The diagnostic significance of assessing the concentration level of cytokines is to ascertain the very fact of its increase or decrease in a given patient with a specific disease, and in order to assess the severity and prediction of the course of the disease, it is expedient to determine the concentration of both pro- and anti-inflammatory cytokines in the dynamics of pathology development.

Reference values, pg / ml > 10,0

Indications for prescription
In-depth study of the features of the immune status;
allergic diseases;
chronic hepatitis C;
evaluation of the effectiveness of the treatment;
prognostic criterion of development of infectious-inflammatory process
Interpretation of results
Level up
Allergic reactions (bronchial asthma, atopic dermatitis, pollinosis);
Sézary syndrome;
chronic hepatitis C, acute phase

Level down

Malignant neoplasm;

viral, protozoal infections

Interleukin 6 (Interleukin-6, IL-6)

Interleukin 6 (IL-6) is a glycoprotein, that is a multifunctional cytokine that coordinates the immune and acute phase inflammatory responses, as well as oncogenesis and hemopoiesis. It is produced by cells of the immune system, as well as by the cells that do not have a direct relationship to the immune system: fibroblasts, keratinocytes, chondrocytes, endometrial stromal cells, Leydig cells in testicles, follicular-stellate pituitary cells and smooth muscle cells of blood vessels, endothelial and synovial cells. IL-6 can also be excreted by tumor cells of different histological nature. Receptors for IL-6 are found on both lymphoid and non-lymphoid cells. One of the main functions of IL-6 is the regulation of the maturation of antibodies producing B-lymphocytes and the production of immunoglobulins. IL-6 acts as a mediator of protective processes against infections and tissue damage. In addition, it is capable of inhibiting the synthesis of proinflammatory cytokines (IL-1β and TNF), it can exert hormone-like effects on the liver, supporting glucose homeostasis, stimulates the secretion of growth hormone and suppresses the secretion of thyroid-stimulating hormone, has pyrogenic properties, reduces the synthesis of albumin and prealbumin. IL-6 is considered to be the most important mediator of the acute phase of inflammation, as it induces the synthesis of acute phase proteins: fibrinogen, alpha1-antihemhemotrypsin, C-reactive protein, haptoglobin, serum amyloid A. IL-6 is constantly present in blood, therefore its concentration is more consistent with expression fever and other manifestations of infection. The possibility of using IL-6 as a marker for early assessment of the severity of acute pancreatitis is shown. The high content of IL-6 allows us to consider this cytokine as a marker of the aggressiveness of the course of the disease in malignant neoplasm of the ovaries, and also to plan the choice of the volume of operative treatment. Determination of IL-6 content in newborns is necessary to confirm bacterial sepsis, since this cytokine has high sensitivity and specificity under such conditions. The concentration of IL-6 in human serum correlates with the body mass index, increasing with obesity and atherosclerosis.

Reference values, pg / ml 1,5-7,0
Indications for prescription
IL-6 – one of the mediators of the acute phase of inflammation
Investigation of the immune status in severe inflammatory diseases, bacterial infections, malignant neoplasms;
acute pancreatitis (early assessment of the severity of the pathological process);
bacterial sepsis in newborns;
autoimmune diseases
Interpretation of results
Level up
Essential thrombocythemia;
severe inflammation, infection and trauma;
autoimmune diseases (rheumatoid arthritis);
myxoma heart;
Castleman’s disease;
mesangioproliferative glomerulonephritis;
Kaposi’s sarcoma;
liver disease (alcoholic cirrhosis, viral hepatitis, primary biliary cirrhosis);
kidney damage (with lymphoma, myeloma, carcinoma);
exacerbation of peptic ulcer of stomach and duodenum;
acute pancreatitis;
gluten enteropathy;
Crohn’s disease;
Kawasaki syndrome

Component of complement C3

The complement component of C3 is the central component of the complement system, the acute phase protein of inflammation necessary for the realization of cytolysis and anaphylaxis. It constitutes 70% of the total protein of the complement system, is synthesized in the liver, macrophages, fibroblasts, lymphoid cells and skin, participates in the activation of complement both in a classical way (complexes with IgG, IgM), and in alternative way (antigen complexes with IgA, IgE, Fab- fragments of Ig, polysaccharide antigens of bacteria). Activation of C3 promotes the release of histamine from mast cells and platelets, supports phagocytosis, enhances the permeability of the vessel walls, enhances the contraction of smooth muscle, leukocyte chemotaxis, and the combination of antibodies with antigen; plays an important role in the development of autoimmune diseases. Hereditary defects C3 are a rare anomaly transmitted autosomally recessively, which is characterized by clinically recurrent infections caused by both gram-positive and gram-negative bacteria (pneumonia, meningitis, impetigo). Testing can detect both the biologically active fraction and the inactive fraction of C3.
Transport environment

Reference values, g / l 0,9-1,8
The recalculation factor g / l x 100 = mg / dL; mg / dl x 0.01 = g / l
Effect of medication
Cimetidine, cyclophosphamide, oral contraceptives


Hydralazine, methyldopa

Indications for prescription
C3 is the central component of the complement system, the acute phase protein of inflammation
• Suspicion of genetic deficiency of complement in autoimmune diseases, recurrent bacterial infections;
• Monitoring of SLE and other autoimmune diseases;
• Inflammatory and infectious diseases of various etiologies
Interpretation of results
Increasing the level
• Inflammatory and infectious diseases of various etiologies;
• systemic diseases of connective tissue (rheumatoid arthritis, rheumatism);
• diabetes;
• myocardial infarction;
• Gastrointestinal diseases (obstructive jaundice in viral hepatitis, ulcerative colitis, inflammatory bowel disease);
• neoplasms;
• Thyroid gland diseases (thyroid goitre, thyroiditis);
• sarcoidosis, amyloidosis

Decreasing the level

  • Hereditary insufficiency C3, deficiency factor-inhibitor activator C3b;
    • Various inflammatory and infectious diseases (subacute bacterial endocarditis, viremia, parasitemia, bacterial sepsis);
    • active phase SLE;
    • severe liver damage (viral hepatitis B);
    • combined essential cryoglobulinemia;
    • Sjogren’s syndrome;
    • serum sickness;
    • syndrome of the shortened small intestine;
    • membranous-proliferative, post-streptococcal glomerulonephritis;
    • Atheromatous embolism;
    • hereditary Mediterranean fever accompanied by hives and vasculitis;
    • X-linked hypoglobulinemia;
    • hemolytic-uremic syndrome;
    • DIC-Syndrome;
    • AIDS;
    • Concomitant conditions (anorexia nervosa, celiac disease, uremia)

Component of complement C4-2.

C4 is a component of the complement system, which is synthesized in the liver, lungs and bones. C4 is used only for the classical pathway of complement activation, so that its level is normal under conditions related only to activation involving alternative complement pathways. Concentrations of C4 in serum are a sensitive indicator of the degree of activity of diseases accompanied by the formation of cells of red lupus erythematosus (LE-cells). The presence of C4 is necessary for the realization of phagocytosis reactions. The definition of C4 is important for the diagnosis of immune diseases, in which it is adsorbed on immune complexes. With hereditary angioedema, the absence of a C1-esterase inhibitor determines the lysis of fractions C2 and C4 with C1-esterase, and the C4 level will be low. Hereditary deficiency of C4 is associated with an increased risk of infection with the pyogenic bacterial flora. The determination of C4, as a rule, is carried out simultaneously with the determination of the C3 complement component and other tests for determining the human immune status. Reduction of the C4-component, along with a decrease in the C3-component, indicates the activation of the classical pathway (which can be observed, for example, in viral hepatitis, the beginning of the formation of immune complexes).               A decrease in blood plasma C4 at a normal C3 level indicates a deficiency of C4 (as in congenital angioneurotic edema and in some forms of systemic lupus erythematosus).

Research method. Preparation rules. General clinical and biochemical blood tests. General and biochemical blood tests.

Material for research
Transport environment

Reference values, g / l     0,1-0,4
The conversion factor mg / dl x 0.01 = g / l; g / L x 100 = mg / dl; mg / dl x 0.050 = μmol / L; g / l х 5,0 = μmol / l
Effect of medication

Cyclophosphamide, oral contraceptives


Dextran, methyldopa, penicillamine

Indications for prescription
C4 complement component – an indicator of the protective function of the body in infectious and autoimmune diseases
• Assessment of the degree of activity of SLE;
• hereditary angioedema;
• malignant neoplasms;
• diseases of immune complexes;
• recurrent severe infections;
• control of treatment with immunosuppressants and cytostatics
Interpretation of results
Increasing the level
• Hereditary deficiency of components C1q, C1r, C1s;
• malignant neoplasms;
• Conditions accompanied by acute inflammatory response (with adequate immune response)

Decreasing the level

  • Hereditary causes (C4 deficiency, hereditary angioedema);
    • diseases of immune complexes (rheumatoid arthritis, SC (active forms), autoimmune thyroiditis, systemic vasculitis, kidney transplantation, glomerulonephritis, autoimmune hemolytic anemia, liver damage);
    • cryoglobulinemia

Complement C1q of circulating immune complexes, autoantibodies

Anti-C1q Antibody

Antibodies of class IgG to C1q are responsible for the formation of immune complexes. C1q is a glycoprotein consisting of 18 polypeptide chains and three unidentified subunits, in combination with two C1r and two C1s molecules forms the first complement component (C1). Activation of complement by the classical pathway is triggered when C1q is bound to immune complexes or to various other activating substances. After C1q binding, conformational rearrangement of C1r and C1s occurs to proteolytic enzymes, which correspond to 4J for the continuation of activation along the classical pathway. In 1984, autoimmune antibodies to C1q in the serum of patients with systemic lupus erythematosus (SLE) were detected. These antibodies are found in large numbers in autoimmune diseases and kidney diseases. It was found that the presence of autoimmune antibodies to C1q is directly related to the disease of immune complexes, especially with hypocomplementary urticarial vasculitis (the presence of antibodies to C1q is the main criterion) and diffuse proliferative lupus nephritis. Although it has not been proven that the availability of these antibodies to C1q is a diagnostic criterion for any of these diseases, the determination of the content of antibodies to C1q can be a valuable tool in the clinical examination of patients with SLE. Antibodies to C1q were observed in 15-60% of patients with SLE and in 95% of patients with lupus nephritis. A negative result of the determination of antibodies to C1q excludes the risk of kidney inflammation in the following months with a sensitivity of 95% (negative predictive value). In addition, the determination of autoimmune antibodies to C1q is important in monitoring patients suffering from lupus. Successful treatment of active lupus nephritis with immunosuppressive drugs usually leads to a decrease in the content of these antibodies. The content of autoantibodies to C1q only slightly correlates with the content of antibodies to double-stranded DNA, but directly correlates with the content of C1q antigen.

Research method. IFA

Preparation rules. General and biochemical blood tests. General clinical and biochemical blood tests

Material for research

Transport environment

Reference values, RU / mL
Less than 20.0 is a negative result. Greater than or equal to 20.0 – positive result
Indications for prescription
• Autoimmune diseases, systemic connective tissue diseases, vasculitis, immune complexes disease;
• monitoring of the course and assessment of the risk of kidney damage in SLE;
• Diagnosis of hypocomplexary urticarial vasculitis;
• evaluation of the effectiveness of treatment of lupus nephritis (lupus jade)
Interpretation of results
Positive result
• SLE with a 50% chance of developing kidney damage in the next 6 months;
• lupus nephritis (lupus nephritis) in 95% of cases;
• Hypokomplementary urticarial vasculitis;

  • idiopathic membrane-proliferative glomerulonephritis;
    • Felty’s syndrome;
    • IgA-nephropathy

Negative result

  • Eliminates the risk of kidney inflammation in the following months with a sensitivity of 95%

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