Immune complexes (aka circulating immune complexes, or KKIs) form each time specific antibodies come into contact with foreign particles in the body. An efficiently functioning liver and spleen should remove immune complexes on an ongoing basis. However, this is not always the case. In some situations, an excess of immune complexes can activate the immune system, leading to inflammation and tissue damage.

Immune complexes(or antigen-antibody complexes) are physiological structures that are formed in the body by combining immune proteins (antibodies) with a foreign molecule (antigen).

Antigen can be viruses, bacteria, food particles, pollen, and even the body's own proteins (the so-called autoantigens).

The physiological role of immune complexes is to make the antigen visible to the immune system so that it can be safely removed from the body.

Contents:

  1. Circulating immune complexes (KKIs) - can they be dangerous to your he alth?
  2. Circulating immune complexes (KKI) - diseases
  3. Circulating Immune Complexes (KKIs) - diagnostics
  4. Circulating immune complexes (KKI) and Lyme disease

Circulating immune complexes (KKIs) - can they be dangerous to your he alth?

Immune complexes can also be involved in a variety of pathologies. Most often, this condition occurs when immune complexes are not effectively eliminated by macrophages in the liver and spleen.

They can then accumulate in tissues or blood vessels, triggering immunological processes leading to inflammation and subsequent tissue damage.

The complement system is the key element activated by immune complexes. The complement system is a group of proteins whose cascade activation results, among others, in to initiate the inflammatory process.

The deposition of immune complexes in tissues is influenced by a number of factors, such as:

  • Size of immune complexes; especially medium-sized complexes are easily deposited in tissues
  • Class of antibodies and their affinity for the antigen; antibodies in the IgG1 and IgG3 subclasses strongly activate and cause the immune systemtissue damage
  • Local microcirculation; in places where blood flow is disturbed, the complexes are much more easily deposited, e.g. in the glomeruli or organs affected by inflammation
  • Type of tissue; kidneys are particularly prone to "capturing" complexes, because there are many receptors with which immune complexes bind
  • Mutations of genes encoding elements of the complement system, which impede the process of removing immune complexes

Circulating immune complexes (KKI) - diseases

The best known disease associated with the presence of immune complexes is systemic lupus erythematosus (SLE). SLE is an autoimmune disease in which complexes composed of cellular DNA and specific antibodies are deposited in the skin and internal organs, such as the kidneys.

Another example of an immune complex disease is type III hypersensitivity such as allergic alveolitis (the most common forms are farmer's lung or bird grower's lung).

It is an occupational disease of people who have daily contact with mold, fungus and bacterial antigens, e.g. in farms or animal farms. Immunological complexes in the alveoli that adhere to the lungs cause local inflammation that damages surrounding tissues.

Type III hypersensitivity can also include food allergic reactions. In this case, immune complexes are formed from specifically food IgG antibodies and food antigens, causing allergic reactions to foods, the symptoms of which appear several hours after contact with the allergen.

A systemic pathology associated with the formation of immune complexes is serum sickness, which occurs as a result of the body's contact with a foreign antigen. Serum sickness can occur after administration of a tetanus vaccine, drugs containing monoclonal antibodies (e.g. rituximab) or some antibiotics (e.g. penicillin).

The presence of immune complexes is also observed in some viral (e.g. hepatitis B or C virus, Epstein-Barr virus) and bacterial infections (e.g. bacterial endocarditis).

Research shows that atherosclerosis and cardiovascular diseases are another disease process in which immune complexes may contribute. In this case, the antigens that form the complexes are molecules of the so-called bad LDL cholesterol, which intensify the inflammatory processes within the plaqueatherosclerosis.

Circulating Immune Complexes (KKIs) - diagnostics

Histological examinations using fluorescent or enzymatic techniques directly detect the presence of immune complexes in tissue sections.

C1q binding assay, evaluates the amount of circulating immune complexes containing IgG antibodies to which the complement C1q protein non-specifically binds; the test is performed using the ELISA method from venous blood; valid values ​​are<4μgE/ml.

Raji cell line assay assesses the amount of circulating immune complexes associated with the complement element C3; the test consists in determining the amount of immune complexes in the patient's blood by means of ELISA or flow cytometry, which, after incubation in cell culture, bind to cells of the Raji lineage; correct values ​​depend on the method used and are usually<15-25 μgE/ml.

Testing for the presence of immune complexes in the body is not a frequently used test. This is due to the lack of standardization of the methods used and the restrictive conditions for collecting the material.

Circulating immune complexes (KKI) and lyme disease

Detecting the presence of immune complexes has been used in the diagnosis of Lyme disease. The excess of immune complexes consisting of Borrelia burgdorferi antigens and their specific antibodies may make it impossible to detect them using serological methods.

This problem occurs mainly in very intense infections, when a large number of immune complexes are formed.

If the patient has symptoms of Lyme disease, and the results of serological tests are negative, then he can be tested by chemical breaking down immune complexes.

This procedure is aimed at releasing antibodies from the complexes and only measuring their serum concentration. However, this method is not used routinely due to the lack of standardization in laboratories.

References:

  1. Immunology, edited by Gołąb J., PWN 2012
  2. Internal diseases, edited by Szczeklik A., Medycyna Praktyczna Kraków 2005
  3. Burut D.F. et al. The role of immune complexes in atherogenesis. Angiology. 2010 Oct; 61 (7): 679-89.
  4. Theofilopoulos A.N. et al. The Raji cell radioimmune assay for detecting immune complexes in human sera. J Clin Invest. 1976 Jan; 57 (1): 169-182.
  5. Lock R.J. and Unsworth D.J. Measurement of immune complexes is not useful in routine clinical practice. Ann Clin Biochem. 2000; 37: 253-61.
  6. Marques A. R. Laboratory Diagnosis of LymeDisease - Advances and Challenges. Infect Dis Clin North Am. 2015; 29 (2): 295-307.
About the authorKarolina Karabin, MD, PhD, molecular biologist, laboratory diagnostician, Cambridge Diagnostics Polska A biologist by profession, specializing in microbiology, and a laboratory diagnostician with over 10 years of experience in laboratory work. A graduate of the College of Molecular Medicine and a member of the Polish Society of Human Genetics. Head of research grants at the Laboratory of Molecular Diagnostics at the Department of Hematology, Oncology and Internal Diseases of the Medical University of Warsaw. She defended the title of doctor of medical sciences in the field of medical biology at the 1st Faculty of Medicine of the Medical University of Warsaw. Author of many scientific and popular science works in the field of laboratory diagnostics, molecular biology and nutrition. On a daily basis, as a specialist in the field of laboratory diagnostics, he runs the content department at Cambridge Diagnostics Polska and cooperates with a team of nutritionists at the CD Dietary Clinic. He shares his practical knowledge on diagnostics and diet therapy of diseases with specialists at conferences, training sessions, and in magazines and websites. She is particularly interested in the influence of modern lifestyle on molecular processes in the body.

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