Circulating immune complexes (CEC, 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. It's 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, which are concentrated in excess in the blood.

As already mentioned, the process by which circulating immune complexes are formed is the norm. human body. However, again, until 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 norm of their concentration is 30-90 IU / ml. Excess upper bound suggests that, perhaps, a systemic disease develops in the body. In particular, the connection of this phenomenon with the development of systemic lupus erythematosus has been proven. It is also an indication of the development of immune pathology. Circulating immune complexes, the norm of which is exceeded, can also appear in addition to blood in other biological fluids. This process is indicative 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 a roulette wheel. Today, antibodies coped with the antigen, destroyed it and disposed of the remains, and tomorrow such a strong antigen entered that the immune system simply could not cope with it. started pathological process. By the time we realized that the body is sick and established the cause of this, the disease has already deeply taken root, 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 let antigens into the body. It sounds very simple and logical, but, unfortunately, it is very difficult to implement in modern conditions our aggressive environment. The fact is that immediate destruction by immune cells only those antigens about which it is precisely known that this is an enemy are subject. When the immune system is not familiar with the newly arrived unicellular 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.

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Determination of circulating immune complexes in the blood– analysis aimed at quantitative research high molecular weight compounds formed from specific immunoglobulins and antigens at their high concentration. An elevated level of CEC in the blood indicates the 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, infectious disease. The study is used to diagnose and monitor allergic, autoimmune and chronic infectious diseases, glomerulonephritis. The biomaterial is serum venous blood. Enzyme immunoassay methods are used to perform the analysis. Norm values ​​- 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 CEC level also increases. Phagocytes and excretory organs do not cope with their functions to the fullest. There is an accumulation of circulating immune complexes in tissues and organs, they are damaged, inflammation develops. This condition is called immune complex disease or type III hypersensitivity. The deposition of the CEC is typical for inner walls blood vessels, glomeruli, joints. Clinically, it manifests itself as symptoms of vasculitis, glomerulonephritis, 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 prolonged persistent infections, in clinical practice elevated level CEC is a sign of inflammation in the body, an indicator that reflects the activity of an autoimmune disease. Blood for analysis is taken from a vein. Research is being done ELISA methods. The obtained indicators are used in diagnostic purposes, as well as to control the course of diseases in rheumatology, immunology, allergology, nephrology.

Indications

The study of circulating immune complexes is used to detect and control diseases, the pathogenesis of which is based on the mechanism of type III hypersensitivity. It is indicated for patients with allergic and autoimmune pathologies, chronic persistent infections, lesions of the renal glomeruli (glomerulonephritis). The basis for the appointment of the 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, in the presence of cancer.

The study of circulating immune complexes is a reliable diagnostic tool that reveals pathogenic 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, therefore, 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. Her fence is performed in the morning, before meals. Special training blood donation is not required. For half an hour it is recommended to stop smoking, intense physical activity, avoid emotional tension. Blood is taken from cubital vein puncture method. Delivered to the laboratory in a sealed tube on the same day.

The concentration of circulating immune complexes is determined in the serum of venous blood, therefore, before the study, the tube is placed in a centrifuge. Shaped elements are separated, leaving the liquid part - plasma. Coagulation 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 the CEC to bind to the C1q component of the complement. The resulting complexes increase the density of the test sample, which is measured with 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 approximately 10% healthy people a moderate increase in the level of the 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 other immunological tests.

Raising the level of the CEC

Reducing the level of the CEC

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 amount of CEC in the blood decreases with a decrease in the number of pathogens. Low performance analysis at primary examination are the norm.

Treatment of deviations from the norm

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

Description

Method of determination

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

Material under study Serum

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

An increased intake of foreign antigens, a decrease in tolerance to autoangigen, a violation of the processes of elimination of immune complexes lead to advanced education immune complexes. Such complexes can form directly in tissues when reactive 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 slowed down or filtration occurs, as well as when their solubility decreases), can be deposited on the 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 tissues. The potential pathogenicity of the CEC may depend on the nature of the antigens and antibodies included in their composition, size, rate of formation and excretion, solubility, and ability to bind 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 the CEC is not specific to any individual 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 relevance. CEC studies in dynamics can be useful in monitoring clinical activity and the effectiveness of therapy for certain diseases (including SLE).

There are different methods for determining CEC based on their physicochemical or biological properties. Results different methods do not always correlate with each other. Solid-phase ELISA methods that use the property of the CIC 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 the CEC may still be insufficiently sensitive and specific in the diagnosis of diseases caused by immune complexes, and should be supplemented by the study of potential pathological manifestations the effect of the CIC on the function of organs, as well as an assessment of the activity of the complement system, including the determination of the C3 and C4 components of the complement (), the number of which decreases due to increased consumption in such conditions.

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

Literature

  1. Lapin S.V. Totolyan A.A. Immunological laboratory diagnostics autoimmune diseases/. Publishing house "Chelovek", St. Petersburg, 2010.
  2. Tietz Clinical Manual of Laboratory Tests (Ed. Wu A.), M. Labora, 2013, 1280 pp.
  3. Nephrology. National leadership(editor-in-chief 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 of the company - the manufacturer of reagents.

Training

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 should elapse between the last meal and blood sampling. You can drink water.

Indications for appointment

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

Interpretation of results

The interpretation of test 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:

Boost.

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 apparently healthy people may have a moderately elevated content of the CEC. Result laboratory test cannot serve as the sole basis for making a 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 a soluble form. They are usually excreted by the kidneys or utilized by macrophages. However, with some excess of the antigen, insoluble complexes can form, which precipitate out as a 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 exacerbates 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, by 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 the formation of immune complexes at different antigen-antibody ratios: 1 - an excess of antibodies leads to soluble immune complexes; 2 - an equivalent amount of antigen and antibodies leads to the formation most precipitate; 3 - an excess of 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. It is very important for the formation of memory B cells.

What is 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 the defeat of these cells, increasing the permeability blood vessels. This entails clinical manifestations- swelling, hemorrhage and necrosis at the injection site of the antigen.

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 C3 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 CR-1 erythrocyte receptor and the capture of this entire erythrocyte by a mononuclear phagocyte.

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

Circulating immune complexes in plasma are evidence of the presence of various inflammatory processes in the human body. Thanks to this study, you can find out about the presence of autoimmune diseases and track their activity. A doctor can prescribe such a diagnosis if it is impossible to diagnose a patient for certain reasons, but he has suspicions of the presence of autoimmune viral, fungal and other diseases. The analysis for circulating immune complexes is carried out in 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 hit 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 CEC is impaired, 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 performed their function, they are usually destroyed by phagocytes.

Circulating immune complexes can be formed 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 severely ill 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 seen on early stage, then this can lead to the spread of inflammation to other internal organs abdominal cavity. Often these changes can lead to cancer. The normal content of the CIC in plasma should be 30-90 IU / ml.

When and why is research done?

Analysis is usually used to diagnose general state patient. This is necessary before a major operation, during pregnancy, in the presence of oncological diseases. By such a diagnosis, it is possible to detect the presence in the body immune pathology or a 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 in the course of analysis for circulating immune complexes, they are easy to detect. Such a diagnosis allows you to control the development of glomerulonephritis and adjust its treatment. When the immune system is damaged, a blood test is the best way to follow the trend of the development or cessation of the disease.

Quite often, only such a blood test will allow the doctor to get complete 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 cause is autoimmune pathology at the patient. If a person has a suspicion of arthritis, lupus, polymyositis, vasculitis or scleroderma, then this is a reason to diagnose. She will be able to confirm or refute the diagnosis. Often such a blood test is prescribed for patients with articular syndromes, lesions of cartilaginous tissue and blood vessels, disorders of the kidneys or liver. This analysis is an integral part of the diagnosis in the examination of the immune system.

Increasing the rate in patients

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

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

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

At elevated 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 a study, you need to take an analysis of your blood, which will then be connected to C1q elements. The result will depend on how capable the plasma cells are of interacting with the C1q components.

Reducing the level of elements

A decrease in the amount of CEC entails deviations and destruction of tissues. 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 the 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 be associated with erythrocytes. These links in excess or deficiency do not have a destructive effect and do not cause significant harm to the body, therefore, the study focuses exclusively on the presence of components directly in the patient's blood.

Elemental levels can be checked by reacting to substances C3d and C1g. If the indicators are significantly lowered, then this indicates damage to the gene, which is responsible for the transformation of protein elements in the body. Reduced value speaks of the presence allergic disease, vasculitis, or autoimmune disease. Often this indicator means the presence of hepatitis, HIV, infectious arthritis or endocrite.

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