Circulating immune complexes (CIC, Circulating Immune Complex). Circulating immune complexes

Various antigens constantly penetrate our body and are neutralized immune antibodies. The compound that is formed as a result of this interaction is called circulating immune complexes. This is absolutely normal process, constantly flowing in the human body, provided that the antibodies cope, and the mononuclear phagocytes destroy and utilize the remnants of the destroyed foreign microorganisms. However, if an excess of antigens (viruses, infections, bacteria, etc.) is formed that antibodies cannot cope with, immune complexes are formed, which, settling in blood vessels, kidneys or other organs, cause the destruction of their tissues. Such circulating immune complexes are a major cause of systemic autoimmune diseases. Systemic lupus erythematosus, endocarditis, autoimmune hepatitis, glomerulonephritis - these are the main very dangerous diseases, which cause immune complexes that concentrate in excess in the blood.

As already mentioned, the process by which circulating immune complexes are formed is the norm. human body. However, again, as long as the body copes with antigens. That is, in order for these immune complexes not to harm the body, strong immunity is needed, the response of which to the penetration of antigens can cope with them before they harm human health.

Circulating immune complexes in human blood are associated with erythrocytes, and in this case they can very rarely damage vessels or organs. More dangerous are the free circulating immune complexes in the blood plasma. The normal concentration is 30-90 IU/ml. Excess upper limit indicates that a systemic disease may be developing in the body. In particular, the connection of this phenomenon with the development of systemic lupus erythematosus has been proven. This is also an indication of the development of immune pathology. Circulating immune complexes, the norm of which is exceeded, can also appear in other areas besides the blood. biological fluids. This process is an indication of the development malignant neoplasms or inflammatory processes. However, about such serious illnesses we can talk only in cases where the quantitative indicators of circulating immune complexes are exceeded by 2 or more times.

Roughly speaking, for the human body the formation of circulating immune complexes is roulette. Today the antibodies dealt with the antigen, destroyed it and disposed of the remains, but tomorrow such a strong antigen penetrated that the immune system simply could not cope with it. Started pathological process. By the time we realized that the body was sick and established the cause of this, the disease had already taken deep roots, and, as we learned from this publication, diseases of this nature are very dangerous.

How to avoid such a risk? There is only one way: do not allow antigens into the body. This sounds very simple and logical, but, unfortunately, it is very difficult to implement in modern conditions aggressive environment of our habitat. The fact is that immediate destruction by immune cells Only those antigens that are known to be an enemy are subject to treatment. When the immune system is not familiar with the newly arrived single-celled organism, it does not attack immediately, but reacts with it, forming circulating immune complexes. If the antigen is immediately destroyed, nothing like this happens, therefore, there are no risks.

To give immune cells information about all dangerous antigens, it is necessary to take Transfer Factor. This is the only drug that contains a concentrate of chains consisting of 44 amino acids. These formations contain all the necessary information about dangerous antigens that should not be allowed into the body, but should be immediately destroyed. This information is called immune memory, and it is universal across all mammals. Peptide chains called transfer factors are unique formations that store great amount immune information obtained over millions of years of evolution. 4Life isolates transfer factors from bovine colostrum. Colostrum for all mammals is that indispensable component that contains transfer factors in maximum concentration so that the mother can pass them on to her child.

Today, everyone needs the Transfer Factor drug to restore the functions of immune cells. Adults, children, pregnant women, newborn babies, the elderly - everyone needs to take it. The safety of the drug is confirmed by clinical studies, a letter of recommendation from the Ministry of Health of Russia, 3000 studies and scientific works, as well as the positive experience of receiving thousands of people around the world.

Determination of circulating immune complexes in the blood– analysis aimed at quantitative research high molecular weight compounds formed from specific immunoglobulins and antigens with their high concentration. An increased level of CEC in the blood indicates a risk of their deposition in tissues and the development of inflammation. The analysis is performed during an immunological examination, the results are used in immunology, rheumatology, allergology, and infectious disease. The study is used to diagnose and monitor allergic, autoimmune and chronic infectious diseases, glomerulonephritis. The biomaterial is serum venous blood. To perform the analysis, enzyme immunoassay methods are used. Normal values ​​are up to 20 U/ml. Results are prepared within 3-4 business days.

Circulating immune complexes are compounds that consist of specific immunoglobulins, complement components and antigen. They are formed and circulate in the blood when a foreign agent enters the body. Large CECs are excreted through the liver and spleen, the rest are captured and digested by phagocytes. If a large amount of antigen enters the body, the level of CEC also increases. Phagocytes and excretory organs do not cope with their functions fully. Circulating immune complexes accumulate in tissues and organs, they become damaged, and inflammation develops. This condition is called immune complex disease or type III hypersensitivity. CEC deposition is typical for internal walls vessels, renal glomeruli, joints. Clinically, it manifests itself as symptoms of vasculitis, glomerulonephritis, and arthritis. The pathogenetic mechanisms of autoimmune diseases are associated with the deposition of CEC in organs and tissues.

The number of circulating immune complexes in the blood increases with protracted persistent infections, in clinical practice elevated level CEC is a sign of inflammation in the body, an indicator reflecting the activity of an autoimmune disease. Blood for analysis is taken from a vein. The research is being carried out enzyme immunoassay methods. The obtained indicators are used in diagnostic purposes, as well as for monitoring the course of diseases in rheumatology, immunology, allergology, nephrology.

Indications

The study of circulating immune complexes is used to identify and monitor diseases whose pathogenesis is based on the mechanism of type III hypersensitivity. It is indicated for patients with allergic and autoimmune pathologies, chronic persistent infections, and damage to the renal glomeruli (glomerulonephritis). The basis for prescribing a study may be the presence of articular syndrome, damage cartilage tissue And vascular walls, impaired renal and/or liver function. Sometimes the analysis is performed as part of a comprehensive immunological examination during pregnancy, in preparation for surgery, or in the presence of cancer.

The study of circulating immune complexes is a reliable diagnostic tool that identifies pathogenetic mechanism diseases and reflects the activity of the process. Its importance increases with chronic infections and autoimmune pathologies with erased symptoms - the indicator is considered a marker of the inflammatory process in the body. However, the result of the analysis reflects the amount of CEC in the blood, and not in the tissues, so it is impossible to judge the stage of the disease. Another limitation of the test is its low specificity - an increase in the indicator occurs in many diseases, so data are used to make a diagnosis various studies: laboratory, instrumental, clinical.

Preparation for analysis and collection of material

The material for analysis of circulating immune complexes is blood. Its collection is carried out in the morning, before meals. Special training is not required for the blood donation procedure. Within half an hour, it is recommended to quit smoking, intense physical activity, and avoid emotional stress. Blood is taken from ulnar vein puncture method. Delivered to the laboratory in a sealed tube on the same day.

The concentration of circulating immune complexes is determined in venous blood serum, so before the study the test tube is placed in a centrifuge. Shaped elements are separated, leaving the liquid part - plasma. Clotting factors are removed from it. The resulting serum is subjected to the enzyme immunoassay procedure. In this case, it is based on the ability of CEC to bind to the C1q component of complement. The resulting complexes increase the density of the test sample, which is measured using a photometer. Based on the data obtained, the CEC level is calculated. Preparation of analysis results takes up to 4 business days.

Normal values

The level of circulating immune complexes in the blood normally does not exceed 20 U/ml. Physiological factors do not affect this indicator, but in approximately 10% healthy people a moderate increase in the level of CEC in the blood without other signs of disease is determined. Therefore, the result of this analysis is always interpreted in conjunction with clinical data and indicators of other immunological tests.

Increasing the level of the CEC

Decrease in CEC level

A decrease in the level of circulating immune complexes in the blood has diagnostic value When monitoring diseases, the cause in this case is a positive response to therapy. For example, during infection, the number of CECs in the blood decreases as the number of pathogens decreases. Low performance analysis at initial examination are the norm.

Treatment of abnormalities

The study of circulating immune complexes in the blood has diagnostic significance in various areas clinical practice, allows you to determine the pathogenetic mechanism of diseases, monitor their development, and identify hidden inflammatory processes. With the results of the analysis, you must contact your doctor (immunologist, rheumatologist, allergist, infectious disease specialist).

Description

Determination method

Enzyme-linked immunosorbent assay (ELISA), CEC C1q-binding (IgG)

Material under study Blood serum

Determination of circulating immune complexes capable of activating complement via the classical pathway.

Increased intake of foreign antigens, decreased tolerance to autoangigens, disruption of the processes of elimination of immune complexes lead to advanced education immune complexes. Such complexes can form directly in tissues when provocative the antigen is associated with the corresponding cells and tissues. But if the antigens are soluble and circulate in the blood, there is an increase in the concentration of circulating immune complexes (CIC). Circulating complexes, under certain conditions (where the blood flow is slow or filtration occurs, as well as when their solubility decreases), can be deposited on membranes small vessels and accumulate in tissues. The accumulation of immune complexes, their binding to complement factors and activation of the complement system lead to the induction of local inflammation and damage to organ tissue. The potential pathogenicity of CECs may depend on the nature of the antigens and antibodies included in their composition, size, rate of formation and excretion, solubility, and ability to fix complement.

An increase in the level of the CEC is possible with autoimmune pathologies (for example, systemic lupus erythematosus - SLE, rheumatoid arthritis etc.), a number of chronic infectious diseases, in which the constant production of an antigen by an infectious agent is combined with an immune response to it, proliferative neoplastic diseases, allergic conditions. In itself, an increase in the level of CEC is not specific for any separate disease and is not indisputable evidence of immunocomplex pathology and tissue damage, but if such an increase correlates with observed clinical manifestations and other laboratory changes (for example, signs of increased complement system activation), one can suspect clinical role this factor. Upon receipt positive result it is always recommended to perform a re-examination after a few weeks to assess the persistence of the presence of immune complexes in the circulation and, therefore, their probable clinical significance. Dynamic studies of CEC can also be useful in monitoring clinical activity and the effectiveness of therapy for certain diseases (including SLE).

There are different methods for determining CECs based on their physicochemical or biological properties. Results obtained different methods, do not always correlate with each other. Solid-phase ELISA methods using the property of CEC to bind to the C1q component of complement are currently among the preferred and most common, since they allow the detection of potentially pathogenic circulating immune complexes and are more sensitive than PEG precipitation methods. However, it should be taken into account that the study of CEC may still not be sensitive and specific enough in the diagnosis of diseases caused by immune complexes, and should be supplemented by the study of potential pathological manifestations the effect of the CEC on organ function, as well as assessing the activity of the complement system, including the determination of C3 and C4 complement components (), the number of which is reduced due to increased consumption in such conditions.

Limits of detection: 0.1 U/ml - 200 U/ml

Literature

1. Lapin S.V. Totolyan A.A. Immunological laboratory diagnostics autoimmune diseases/. Publishing house "Man", St. Petersburg, 2010.
2. Tietz's clinical manual on laboratory tests (ed. Wu A.), M. Labora, 2013, 1280 pp.
3. Nephrology. National leadership(Chief editor: Mukhin N.A.).. M., GEOTAR-Media, 2014, 608 p.
4. Podolska M.J. et al. Inflammatory etiopathogenesis of systemic lupus erythematosus: an update. Journal of Inflammation Research. 2015, Vol.:8, P. 161-171.
5. Materials from the company - the manufacturer of the reagents.

Preparation

On the eve of the study, it is necessary to exclude physical exercise and smoking. Biomaterial should be taken in the morning from 8 to 10 am on an empty stomach. At least 8 hours must pass between the last meal and blood collection. You can drink water.

Indications for use

1. Autoimmune diseases with an increase in the synthesis of immunoglobulins: SLE, Sjögren's syndrome, rheumatoid arthritis and other systemic diseases.
2. Immune complex vasculitis.
3. Glomerulonephritis of various origins.
4. Infectious processes.

Interpretation of results

Interpretation of research results contains information for the attending physician and is not a diagnosis. The information in this section should not be used for self-diagnosis or self-treatment. Accurate diagnosis puts the doctor, using both the results of this examination¤, and the necessary information from other sources: anamnesis, results of other examinations, etc.

Units of measurement in the Independent Laboratory INVITRO: U/ml

Reference values:< 20 Ед/мл

Interpretation of results:

Promotion.

An increase in CEC concentration is possible with various systemic disorders, including autoimmune disorders, viral and bacterial infections, allergic diseases, oncological pathology. It should be noted that approximately 10% of practically healthy people may have moderately elevated CEC levels. Result laboratory test cannot serve as the sole basis for diagnosis and should always be considered in conjunction with clinical data and the results of other studies.

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Immune complexes formed as a result of the interaction of antibodies with an antigen exist, as a rule, in soluble form. They are usually excreted by the kidneys or utilized by macrophages. However, with some excess of antigen, insoluble complexes can form and precipitate. The inability of phagocytes to eliminate these precipitates (as a result of low activity or their inability to bind certain classes of antibodies, IgA, for example) also sharply aggravates these processes. Most often, immune complexes are deposited on the endothelium of the vascular walls and on the basement membrane.

The formation of antigen-antibody immune complexes can also enhance or inhibit the immune response. Immune complexes, activating complement, are able to stay longer on follicular dendritic cells and more effectively activate B cells. All this enhances the adaptive immune response of the humoral type.

Scheme of formation of immune complexes at different antigen-antibody ratios: 1 - excess antibodies lead to soluble immune complexes; 2 - an equivalent amount of antigen and antibodies leads to the formation the largest number precipitate; 3 - excess antigen leads to soluble1 complexes.

Activated by interaction with the immune complex.

The resulting cytotropic antibodies, cytotoxic immune complexes and effector lymphocytes damage tissues, and the biogenic amines released in this case cause pathophysiological reactions and, ultimately, the development of clinical manifestations of allergic disease.

The drug and the specific antibody form immune complexes that attach to the red body membrane and cause damage.

It has been proven that antibodies and immune complexes can be the cause of some diseases. Therapy for many of these immunologically mediated diseases involves the use of immunosuppressants that non-specifically suppress the host's immune system. Another method of therapy may be the specific removal from the circulation of immune substances, which are pathological in this disease. Shenkane et al. removed anti-BSA antibodies from the plasma of positively immunized rabbits by passing their blood through an immunosorbent prepared by binding BSA to bromoacetylcellulose.

The localization of immune complexes in the centers of reproduction of lymph nodes also depends on the complement. This is very important for the formation of memory B cells.

What is an antigen, antibody, immune complex.

The Arthus phenomenon associated with the fixation of immune complexes on endothelial cells. The mechanism described above ( type III) leads to damage to these cells, increased permeability blood vessels. This entails clinical manifestations- swelling, hemorrhage and necrosis at the site of antigen injection.

Hypersensitivity of the immunocomplex type, due to the formation of IgG immune complexes with a soluble antigen.

Complement is involved in the processing (destruction) of immune complexes due to their binding to the S3 component.

This ensures blood purification from circulating bacteria and immune complexes. Moreover, this purification can occur directly, upon contact of an opsonized bacterium and a phagocyte, or it can be mediated through the binding of bacteria to the erythrocyte receptor CR-1 and the capture of this entire erythrocyte by a mononuclear phagocyte.

The phenomenon is based on a reaction to local formation large quantity immune complexes formed during the interaction of the introduced antigen with accumulated antibodies.

Circulating immune complexes in plasma are evidence of the presence of various inflammatory processes in the human body. Thanks to such research, you can find out about the presence of autoimmune diseases and monitor their activity. A doctor can prescribe such a diagnosis if it is impossible to diagnose the patient for certain reasons, but he suspects the presence of autoimmune viral, fungal and other diseases. Analysis of circulating immune complexes is carried out among both adults and children. The study can be performed as a separate procedure or in a group with other blood tests.

CEC are components that begin to be produced by the human body and are formed in the blood as a response to exposure to foreign bodies. Such complexes usually include antigens, antibodies and other elements. If a person does not have an appropriate reaction and the production of the central nervous system is disrupted, then this indicates that a malfunction has occurred in the patient’s body immune system. The main task of such components is to recognize and remove harmful bodies and allergens from the body as quickly as possible. After the CECs have completed their function, they are usually destroyed by phagocytes.

Circulating immune complexes can form not only directly in the blood, but also in the liver. When they are no longer needed, they are removed from the body. If a person is very sick, stricken infectious disease, then the level of components increases significantly. In this case, they begin to be deposited on the liver and eventually form a dense film, which provokes the formation of an inflammatory process. If such a lesion was not noticed on early stage, this can lead to the spread of inflammation to other internal organs abdominal cavity. Often such changes can lead to cancer. The normal content of CEC in plasma should be 30-90 IU/ml.

When and why is research performed?

The test is usually used to diagnose general state patient. This is necessary before undergoing a major operation, during pregnancy, if there is oncological diseases. Through such diagnostics it is possible to detect the presence in the body immune pathology or severe allergic reaction.

Chronic infections that are in the human body may not manifest themselves on the external plane and are not accompanied by bright severe symptoms, but are easily detected by circulating immune complex assays. Such diagnostics make it possible to monitor the development of glomerulonephritis and adjust its treatment. In case of damage to the immune system, a blood test is the best way to monitor the trend of development or cessation of the disease.

Quite often, only such a blood test will allow the doctor to obtain full picture the course of all allergic and viral processes in the body. The analysis is carried out more than once. If the diagnosis is part of a study of the state of the immune system, then the analysis will have to be repeated several times. During the treatment period, the patient does not need to follow a diet or resort to additional measures preparation for analysis. The process of donating blood can be quite painful, but these sensations disappear immediately after the procedure.

The doctor may prescribe such a diagnosis in several cases. Often the reason is autoimmune pathology at the patient. If a person suspects arthritis, lupus, polymyositis, vasculitis or scleroderma, then this is a reason to conduct a diagnosis. She will be able to confirm or refute the diagnosis. Often such a blood test is prescribed to patients with joint syndromes, damage to cartilage tissue and blood vessels, disorders of the kidneys or liver. This analysis is an integral part of the diagnosis when examining the immune system.

Increased rate in patients

In addition to the fact that circulating immune complexes are created by the human body, they are also destroyed by it. Phagocytes begin to influence those bodies that have already completed their protective function, and destroy them. But if the patient autoimmune disease, this means that either the body produces too many antibodies at one time, or they are not destroyed after they have completed their task.

If the CEC produces too much, then they lose all their properties. As a result, the human body contains many elements that cannot protect it and at the same time provoke inflammatory processes. Unused or excess circulating immune complexes begin to deposit on human organs. The kidneys suffer the most. They are covered with a layer of elemental cells, and their function is hampered. Inflammation begins, which can lead to the progression of diseases, tissue destruction or partial atrophy of the organ.

Formation of antibodies necessary process which must occur in the body. When excess content complexes and disruption of their functioning, viruses and allergens can enter the body, which nothing can resist. At that time human body particularly susceptible various diseases. Even the simplest ARVI can cause serious damage and transform into another disease.

At increased content In the blood of complexes in the human body, the formation of not only inflammatory processes, but also tumors is observed. Such diseases and neoplasms can lead to the development of pathologies and serious damage to the immune system and all internal organs. In order to conduct the study, you need to take a test of your blood, which will then be combined with C1q elements. The result will depend on how able the plasma cells are to interact with the C1q components.

Reducing the level of elements

A decrease in the number of CECs entails deviations and tissue destruction. Insufficient production of elements provokes diseases of the immune system, since now the body cannot independently protect itself from harmful factors from the outside. If complexes an insufficient amount, then this leads to their accumulation on individual bodies. Substances lose their basic functions and grow on the tissues of the body, while destroying it. This occurs due to cell breakdown and a decrease in the density of vascular walls. As a result, the content of CEC in tissues increases and phagocytes can no longer break them down.

CECs can be found not only independently in the patient’s plasma, but also in association with red blood cells. These links, in excess or deficiency, do not have a destructive effect and do not cause significant harm to the body, therefore, during the study, attention is paid exclusively to the presence of components directly in the patient’s blood.

The level of elements can be checked by reaction to substances C3d and C1g. If the indicators are significantly reduced, then this indicates damage to the gene that is responsible for the transformation of protein elements in the body. Reduced value indicates the presence allergic disease, vasculitis or autoimmune lesion. Often this indicator means the presence of hepatitis, HIV, infectious arthritis or endocrit.