Circulating immune complexes (CEC) concept, norm in blood analysis, increase

Circulating immune complexes are always present in some quantities in the body, they are formed during any normally occurring immune reaction, originating from the contact of AH and AT (antigens and antibodies), that is, their formation is a constantly occurring physiological process, because the immune system “is not asleep. “

A single CEC norm, as in the case of other studies, does not exist. After all, each laboratory, based on the methods of conducting a blood test for the CEC (or other biological fluid), determines its norm parameters, which are most suitable for the examined population. The number of CECs is measured in RU / mL (RU – relative units) or in arbitrary units (cu).

Based on the method for determining the CEC and reference values, which establish the normal boundaries of many laboratory studies, including immunological ones, some variants of the norm can be given:

However, it is better for patients who have received blood tests for CEC on their hands not to take these norm indicators as a basis and not to focus on them, the decryption is carried out by a doctor who will help to understand the results of the study. The questions of defining and decoding tests will be covered below, but first, the reader may want to find out how the immune system behaves in certain situations, why immune complexes are formed and what it means if their levels are elevated.


It is known that when a foreign agent (virus or bacteria) enters the body, a whole cascade of immune reactions is observed aimed at protecting and destroying it. A specific response is mediated by antibodies that are synthesized by B-lymphocytes. Immunoglobulins (Ig M and G) bind to antigens, forming specific compounds found in the blood – the CEC.

The immune system responds .

The immunity system can distinguish between its own material and genetically alien substances. These abilities, formed at the dawn of evolutionary development, formed the basis of protective mechanisms that allow you to recognize and then destroy what is not suitable for the body in its properties. If our immune system was not constantly on the alert, it is hard to imagine what would become.

  1. In the first case, if the antigens are “familiar”, but not foreign to the body, what is happening inside us, we simply don’t notice;
  2. On the contrary, in response to the appearance of the “enemy”, the immune system “declares war” and then the development of a violent immune reaction cannot be avoided;
  3. However, it also happens that the proteins of one’s own body fall into the category of “enemies”, they are called autoantigens. Antibodies by which the immune system responds to its own antigens are called autoantibodies (autologous or autoaggressive, since they are directed to their own antigens) – this is the reason for the development of autoimmune processes;
  4. Cases are not excluded when the antigen seems to be alien to the body, but for some reason the immune system does not notice it, such tolerance of the alien is called immunological tolerance (this phenomenon, in general, has little relation to the topic of the CEC, the example is just for clarification some concepts).

In the process of interaction of antigens and antibodies, other proteins are involved that never leave the blood, in order to help implement an immune response, if necessary. This is a system of proteolytic enzymes, a complement system – it is very important for the body, its components also fight foreign agents, providing protection at the level of humoral immunity.


The study is conducted to quantify the content of CEC in the blood. This is an important indicator of the function of the immune system. Preparation for the analysis involves several points:

  • Conversation with the patient about the need for a test.
  • You should follow a normal diet.
  • It is better to come to take blood on an empty stomach.
  • Do not smoke half an hour before the procedure.

If a person passes the analysis for the first time, then it is necessary to accompany each stage of its implementation with an explanation. Blood is taken from the ulnar vein after the skin is treated with an antiseptic. It is filled with a regular or special test tube (vaktaytiner). The injection site is closed with a cotton towel and bent arm to stop bleeding.

The material is then sent to the laboratory, where it is centrifuged to separate the serum. It is used for further identification of antigen-antibody compounds. An enzyme-linked immunosorbent assay (ELISA) is the preferred method for their determination. It consists in the fact that the patient’s serum samples are added to the wells of a special tablet with pre-applied polyclonal antibodies.

How do the CEC behave under normal conditions, which tasks

IR is formed at every meeting of the antigen with the antibody with the participation of complement components, so that they soon become absorbed by phagocytes. In the constantly occurring physiological reaction of the occurrence of the CEC, 2 mechanisms take part:

  • The formation of the immune complex “antigen-antibody” due to specific contact;
  • Slow IR formation accelerated by a nonspecific compound using Fc fragments.

The complement system, also involved in the formation of complexes, causes secondary changes in them. Interaction with component C3 inhibits the reaction between Fc structures, which prevents the development of a pathological process.

IRs that have arisen in the bloodstream bind to C3 receptors on cells that circulate in the bloodstream (for example, red blood cells) and are transferred to the cells of the phagocytic mononuclear system system, which ensures their immediate destruction and removal from the body. In addition, the metabolism of immune complexes circulating in the blood is also carried out in the hepatic parenchyma.

Immune complexes begin to play a pathogenetic role under some special conditions – then they are formed in larger than necessary quantities.

Basically, circulating immune complexes are removed by C-receptors, however, sometimes with some complement components they may not be very “viable” and will easily disintegrate without significant pathogenic effects. For example, C3b by its presence encourages the formation of terminal IRs, which lose their ability to combine, which, in turn, leads to a decrease in their pathogenic properties.

Pathological reactions to the CEC

The appearance of antigens from the outside (for example, after the penetration of a foreign agent into the body) first activates the activity of the phagocytic mononuclear system, which carries out the fight at the cellular level, which, however, may be insufficient, since the mechanisms of cellular immunity ultimately can not withstand and are blocked.

Then humoral immunity enters the “warpath” – it responds to the presence of enemy proteins by the enhanced formation of antibodies directed against them. This is the main reason for the formation of immune complexes. In other cases, immune complexes can consist only of antibodies, which is explained by a violation of their production in certain pathological conditions. Pathological reactions to freely circulating immune complexes can form if:

  1. The rate of IR formation is greater than the rate of elimination;
  2. There is the formation of immune complexes that are not able to escape by complement-mediated mechanisms (for example, this may concern ICs that contain class A immunoglobulins that activate the complement system in another, alternative way) a similar phenomenon is typical for certain types of jade;
  3. In the body, there is a lack of one or several components of the complementary system, moreover, defects that arise in the way of the classical variant of activation of the complement system are more important than violations of the alternative path. In the presence of insufficiency of the first components of the complementary system, pathological processes associated with IR manifest themselves in the vast majority of cases (up to 90%);
  4. There are functional disorders of the mononuclear phagocytic system (for example, with systemic lupus erythematosus, some types of nephritis, biliary cirrhosis).

IRs that contain immunoglobulin A (IgA) and components of the complementary system are able to penetrate small blood vessels (capillaries, arterioles), accumulate there, causing inflammatory reactions that affect the state of the walls of blood vessels and nearby tissues. Immune complexes that are not destroyed in a timely manner by phagocytes, being deposited in organs and tissues and stored there for a long time, are not at all useful for the body.

The most “running” immunological method

Immune complexes that circulate freely in the blood or are fixed in tissues can be identified due to their physical (change in size and solubility) and biological properties (IRs are equipped with structures that “know how” to interact in a certain way with free molecules or with receptors on the cells).

The most “running”, the most common and quite diagnostically significant method for determining circulating immune complexes is enzyme-linked immunosorbent assay (ELISA). This is understandable: almost all clinical diagnostic laboratories are provided with analyzers, test systems are also available to most. Therefore, ELISA is very helpful both in the diagnostic plan (detection of acute inflammatory and allergic reactions of type III, autoimmune processes), and in the treatment (evaluation of the effectiveness of the therapeutic effect in certain pathological conditions of an immune nature).

Indications for the use of a blood test for the CEC are:

  • Autoimmune processes (cryoglobulinemia, systemic lupus erythematosus, Sjogren’s syndrome, disease of immune complexes, etc.), their diagnosis and monitoring of the course and treatment;
  • Diffuse connective tissue diseases (in patients suffering from rheumatoid arthritis – RA, elevated CEC values ​​suggest the formation of a systemic rheumatic process);
  • Persistent infections of viral, bacterial and fungal origin;
  • Inflammatory kidney disease;
  • Suspicion of immunodeficiency;
  • Allergic reactions;
  • Monitoring the course, assessing the degree of risk of complications and the effectiveness of the therapy in the case of pathology associated with a violation in the immune system.

The determination of CECs formed by exogenous and endogenous substances and immunoglobulins directed to them is most often based on the reaction of selective precipitation (precipitation) with PEG (polyethylene glycol) in the wells of a stripped panel (plate). At the same time, given the heterogeneity of the forms of IR circulating in the blood, it is very advisable to resort to other (several) methods of research, where the method of binding freely circulating IR to the C1q component of the complementary system is recognized as the most reliable.

Of course, after testing the decoding of the results will follow, which is the responsibility of the laboratory diagnostics doctor and immunologist. They will interpret the results obtained depending on the numerical values, comparing them with the standard options, and on what they are looking for. If, for example, a patient suffers from systemic lupus erythematosus, and indicators in a blood test for the CEC are increased, then with a 50% probability the doctor will assume that the disease will reach the kidneys within six months.

When and why is the study done?

The analysis is usually used in order to diagnose the general condition of the patient. This is necessary before a major operation, during pregnancy, in the presence of cancer. By such a diagnosis, it is possible to detect the presence of an immune pathology or a strong allergic reaction in the body.

Chronic infections that are in the human body may not manifest themselves on the external plane and are not accompanied by pronounced symptoms, but during the analysis for circulating immune complexes they are easy to detect. Such a diagnosis allows you to monitor the development of glomerulonephritis and adjust its treatment. For damage to the immune system, a blood test is the best way to monitor the development or cessation of a disease.

Quite often, only such a blood test will allow the doctor to get a complete picture of the course of all allergic and viral processes in the body. The analysis is carried out more than 1 time. If the diagnosis is part of the 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 to prepare for the analysis. The process of blood donation 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 an autoimmune pathology in a patient. If a person has a suspicion of arthritis, lupus, polymyositis, vasculitis or scleroderma, then this is an occasion to diagnose. She will be able to confirm or refute the diagnosis.

Increase indicator and its value

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

Normal indicators of CEC concentration are from 0 to 120 conventional units (c.u.).

  • a moderate increase in CEC is characteristic of acute infectious diseases (it is a variant of the norm);
  • autoimmune diseases;
  • exogenous allergic alveolitis;
  • serum sickness;
  • endocarditis;
  • Crohn’s disease;
  • some types of malignant tumors;
  • Artyus phenomenon.

During the interpretation of the indicators, it is necessary to correlate their level with clinical symptoms, since approximately 10% of healthy people may experience an increase in CEC. The reliability of the result is significantly affected by the presence in the blood of cryoglobulins, anti-C1q antibodies.

In addition to the fact that the body creates circulating immune complexes, it also destroys them. Phagocytes act on bodies that have already fulfilled their protective function, and ultimately destroy them. However, with an autoimmune disease in a patient, this means that the body either produces too many antibodies at a time, or they do not break down after completing their task.

In the development of many CECs, they lose their inherent properties. As a result, a large number of elements are found in the human body that cannot protect it and provoke inflammation processes. Excessive or unused circulating immune complexes settle on human organs. Especially affected are the kidneys, which are covered with a cellular layer of elements, which makes their functioning more difficult. An inflammatory process begins that can cause disease progression, tissue destruction, or a partial degree of organ atrophy.

The formation of antibodies is the desired process that should be in the body. With an excessive number of complexes and malfunctions of their functions, allergens and viruses can penetrate the body, which will have nothing to oppose. The human body in this period is especially susceptible to numerous diseases. Even ordinary SARS can cause significant disturbances and develop into another pathology.

If the complexes in the blood of a person are in high numbers, then the formation of both inflammatory processes and tumors is observed in the body. Such neoplasms and diseases can cause the development of diseases and serious damage to all internal organs and the immune system. To conduct the study, the patient needs to take a blood test, which will then be connected to the C1q elements.

Reasons for the increase

For what reasons can the CEC be raised? Deviations from the norm in a big way can be noted with various diseases. Such pathologies can be divided into 3 groups:

  • allergic reactions;
  • autoimmune processes;
  • infection penetration.

The first group of diseases is caused by the introduction of foreign antigens into the body. With allergies, CECs are formed in an increased amount. The body does not have time to remove these compounds. Such pathologies include:

  • allergic reactions to drugs;
  • serum sickness (hypersensitivity to vaccines, serums and blood components);
  • allergic inflammation of the alveoli of the lungs (reaction to inhalation of allergens);
  • allergy after an insect bite;
  • Dühring’s herpetiform dermatitis (skin lesions with the formation of a vesicle rash).

Autoimmune processes often cause an increase in CEC. In rheumatic diseases, immune complexes are deposited in the tissues and cause inflammation. This is noted with the following pathologies:

  • systemic lupus erythematosus;
  • scleroderma;
  • glomerulonephritis (lupus genesis);
  • rheumatoid arthritis;
  • periarteritis nodosa;
  • Crohn’s disease;
  • Sjogren’s syndrome;
  • systemic vasculitis;
  • autoimmune inflammation of the thyroid gland.

In addition, bacterial, viral and fungal infections can become the cause of increased CEC. When the pathogen enters the body, a large number of antigen-antibody complexes are formed. They are not always completely eliminated from the body and accumulate in plasma. Also, the cause of high levels of CEC are malignant tumors and parasitic pathologies.

Increased immune complexes are noted in patients undergoing organ transplants. In this case, this does not indicate an unfavorable prognosis of the disease.

A decrease in the level of immune complexes circulating in the blood is of diagnostic value in the control of diseases, the reason in this case is a positive response to therapy. For example, when infected, the amount of CIC in the blood decreases, and the number of pathogens decreases. Low analysis rates during the initial survey are normal.

How to pass the analysis and why is it prescribed?

Conventional fasting venous blood is given to determine circulating immune complexes. The only condition: it is advisable in the morning on this day until the test is done not to smoke, and not to exert physical strain, to be in a calm state. Stress and hard work the day before can distort the result. The research method is a modern enzyme-linked immunosorbent assay (ELISA).

In addition to this method, there may be other, older methods for determining the CEC, but not always different methods give the same result. The enzyme-linked immunosorbent assay is based on the ability of these complexes to bind to a specific complement fraction. It allows you to highlight just the very types of complexes that can be potentially pathogenic. This method is more sensitive than previous generation analysis methods, for example, gel precipitation.

But still, taken separately, this CEC blood test is both not sensitive enough and not specific enough when it comes to the diagnosis of autoimmune diseases. In this case, the doctor should prescribe, in addition to the study of circulating immune complexes, an assessment of the complement system, and, first of all, its components such as C3 and C4.

It must be remembered that this analysis, namely the determination of the amount of CEC in the blood, will only show the activity of a particular process, but it will not say anything about where and in what amount complexes were deposited in the tissues. He shows only that part of them that is soluble and is in the blood. Accordingly, based on one such analysis, it is not possible to accurately diagnose.

Decreased content

If the number of CEC decreases, this leads to various deviations and tissue destruction. Inadequate production of elements causes diseases of the immune system, because the body is no longer able to protect itself independently from pathological factors. With insufficient content of complexes, this leads to their accumulation on individual organs. The main functions of substances are lost, they grow on the tissues of the body and destroy it.

This occurs due to cellular decay and a decrease in the density of the walls of blood vessels. As a result, the degree of CEC in the tissues increases, and the phagocytes are no longer capable of cleaving them.

CEC can be present not only independently in the blood plasma, but also bind to red blood cells. These links in deficiency or excess do not have a destructive effect and do not significantly harm the body, therefore, when analyzing, they pay attention only to the presence of elements directly in the human blood.

The level of components can be checked by reaction to substances such as C1g and C3d. With a significant decrease in indicators, we can talk about the defeat of the gene responsible for the transformation of protein elements in the body. A reduced degree indicates the presence of vasculitis, an autoimmune lesion, or an allergic disease. This indicator often indicates the presence of endocarditis, infectious arthritis, HIV or hepatitis.

Preparation for analysis and sampling

The material for analysis of circulating immune complexes is blood. Her fence is performed in the morning, before eating. Special preparation for the blood donation procedure is not required. For half an hour, it is recommended to give up smoking, intense physical exertion, and avoid emotional stress. Blood is taken from the ulnar vein by puncture. 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 test, the tube is placed in a centrifuge. The shaped elements are separated, the liquid part remains – the plasma. Coagulation factors are removed from it. The resulting serum is subjected to an enzyme immunoassay.

In this case, it is based on the ability of the CEC to bind to the C1q complement component. 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.

Patient Improvement

In addition to the fact that circulating immune complexes are created by the human body, they are destroyed by it. Phagocytes begin to affect those bodies that have already performed their protective function, and destroy them. But if the patient has an autoimmune disease, then this means that either too many antibodies are produced in the body at one time, or they do not break down after they complete their task.

If the CEC produces a lot, 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 settle on human organs. The kidneys are most affected.

The formation of antibodies is a necessary process that must take place in the body. In case of excessive content of the complexes and disruption of their work, viruses and allergens can enter the body, which nothing will resist. At this time, the human body is particularly susceptible to various diseases. Even the simplest SARS can cause serious damage and transform into another disease.

With an 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 a study, you need to take an analysis of your blood, which after that will be connected to C1q elements. The result will depend on how well plasma cells are able to interact with C1q components.

A little about complement

What is a complement system? To protect the body from external invasion of antibodies, as well as phagocytosis, is not enough. In order for both immunity links to work in a consistent and correct manner, constant regulatory work of the so-called complement system is required. This is the name of a large number of different proteins that are constantly in the blood, and trigger a cascade of immunological reactions. We give an example.

Perhaps the most well-known cascade of reactions in the blood is the coagulation mechanism. When a vessel is damaged, a whole chain of reactions is initiated, in which a large number of different compounds take part: prothrombin, coagulation factors. As a result, fibrin forms, which clogs the damaged vessels, stopping bleeding.

The complement system works by a similar mechanism, only the result of its action will be the correct immune response. The complement system includes about 20 different proteins that are formed in the liver (which is why immunity decreases in case of violation of its functions, for example, with cirrhosis in alcoholics). All of them belong to the fraction of gamma – globulins, and make up approximately one twentieth of it.

Many components of this system are capable of uniting into large molecules, which as a result destroy cell membranes and exhibit proteolytic properties. Thus, by gradually activating the complement system, so-called membrane-attacking complexes are formed. These are fairly large compounds that can either destroy target cells, or label them in a special way, and make them accessible to macrophages (tissue leukocytes).

In simple terms, the complement system “marks” pathogens and they become visible to attacking white blood cells. This function from the point of view of immunology is called opsonization. But we are more interested in another function of the complement system, which is called solubilization. This is nothing more than the dissolution of old immune complexes, which is also implemented by the complement system and should be debugged to the smallest detail.

In a healthy body, there is always a reasonable balance between the rate of formation, the CEC norm and the degree of elimination. In case if:

  • More antigens enter the body than is usually the case with the standard course of infectious diseases;
  • They are formed in the body itself;
  • The sensitivity of immunological protection against autoantigens is reduced;
  • The processes of their excretion from the body are disrupted – these circulating complexes are formed in an increased amount directly in the tissues, especially with autoimmune diseases.

This happens if the complexes are insoluble or poorly soluble. If they are soluble well, then, in simple terms, they “clog” the blood. In those places where the blood flow slows down, where filtration mechanisms exist, or with a sudden decrease in the solubility of the complexes, they are deposited on various surfaces. First of all, these are small vessels, renal tissue that filters, lymphatic collectors, and spleen.

Such precipitation of immune complexes leads to their binding by the complement system. That is, she couldn’t remove them from the body by “setting” macrophages on the CEC, but the complement system still tries to draw attention to them, albeit in an awkward way. And the activation of this system leads to the development of a local inflammatory reaction, and inflammation as a result damages the tissues.

Of course, one cannot say that without exception, all CECs are sharply pathogenic. Their ability to alter or damage tissues depends both on the nature of the antigen itself, on the quantity and quality of the produced antibodies, on solubility, on the rate of formation and elimination of complexes – and on the compliment reaction that binds these complexes.

CEC level increase

The reason for the increase in the level of circulating immune complexes in the blood is an excess of antigens – bacteria, viruses, fungi, parasites. In acute infections, a large number of pathogens spread over the body in a short time, antibodies are actively produced in response, and then CECs are formed. Phagocytes, liver and spleen do not have time to process and remove pathogens from the body, so their blood level increases.

With persistent infections, similar processes occur, but antigens arrive for a long time. If the body does not remove CEC from the blood, then they are deposited in organs and tissues. In these cases, type III hypersensitivity (a disease of immune complexes) can be considered as the reason for the increase in the level of circulating immune complexes in the blood.

How is the analysis performed

Blood is taken from a vein for examination. The biomaterial is placed in a sealed tube and delivered to the laboratory. It is centrifuged and the plasma is separated from the shaped elements.

Plasma is examined by the enzyme immunoassay. A special substance, complement C1q, is added to the test tube with blood serum. This is a protein that interacts with the CEC. After that, the density of the solution is measured using a photometer. Based on these data, the number of circulating immune complexes is calculated. Decryption of the analysis can be obtained on hand approximately 2-4 days after the delivery of the sample.

Where are the CECs formed?

Circulating immune complexes can form both directly in the blood and in the liver. If they are unnecessary, they are simply excreted from the human body. If the patient is seriously ill, suffers from an infectious disease, the content of the components increases to a large extent. In this case, they begin to deposit on the liver and eventually form a dense film that provokes the onset of the inflammation process.

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Svetlana Borszavich

General practitioner, cardiologist, with active work in therapy, gastroenterology, cardiology, rheumatology, immunology with allergology.
Fluent in general clinical methods for the diagnosis and treatment of heart disease, as well as electrocardiography, echocardiography, monitoring of cholera on an ECG and daily monitoring of blood pressure.
The treatment complex developed by the author significantly helps with cerebrovascular injuries and metabolic disorders in the brain and vascular diseases: hypertension and complications caused by diabetes.
The author is a member of the European Society of Therapists, a regular participant in scientific conferences and congresses in the field of cardiology and general medicine. She has repeatedly participated in a research program at a private university in Japan in the field of reconstructive medicine.