Laboratory of Clinical Immunology

Head of the Laboratory
Didkovsky, Nikolay Antonovich
Doctor of Medical Sciences,
Professor
Didkovsky, Nikolay Antonovich

Laboratory of Clinical Immunology was founded in 1985 in SRI PCM by the initiative of Prof. Yu.M. Lopukhin. From the very beginning till now, it is led by Didkovsky, Prof., Honored Doctor of Russian Federation. Didkovsky in 1971 defended a Candidate of Sciences dissertation, which he realized under the supervision of Prof. I.A. Kassirski, and which was entitled: “Hereditary hemolytic anemia: thalassemia and abnormal unstable hemoglobins”. The dissertation formed the basis for the Hemolytic Anemia monography. In 1984 he defended a Doctor of Sciences dissertation, “Hereditary forms of chronic non-specific pulmonary diseases”.
Didkovsky is an author of more than 200 science papers on therapy, hematology, pulmonology, immunology, genetics. The range of his scientific interests is very wide. He was the first in identifying two earlier unknown forms of hereditary abnormal hemoglobins, which were given, in the internal registry of hereditary hemoglobinopathies, the names Moskva and Volga. He was the first in Russia to diagnose and describe the hereditary forms of hemolytic anemia, such as hemoglobinopathy H, alpha- and delta-thalassemia. He also was the first in our country to diagnose and describe clinical cases of selective IgA deficiency, pulmonary emphysema caused by alpha-1-antitrypsin deficiency, bronchiectatic disease associated with general variable immunodeficiency, primary ciliary dyskinesia with normal arrangement of internal organs (Kartagener’s syndrome), hereditary angioneurotic edema with altered C1-inhibitor functional activity. Didkovsky is the leading Russian expert who contributed to solving the problem of diagnostics methods for and treatment of aspirin-induced bronchial asthma.
In 1987, the Republican Center of Extracorporeal Treatment Methods affiliated with the laboratory was founded to investigate, develop, implement and introduce extracorporeal treatment methods (ECTM), among them, in the first place, non-specific hemosorption, plasmapheresis and quantum medicine methods for treatment of allergic and immune diseases. Its current head is V.V. Komov, Candidate of Medical Sciences, a clinical assistant professor, one of the leading experts in hemosorption. The major research and practical work of the Center’s staff is addressing the investigation, development, implementation and introduction of extracorporeal treatment methods (ECTM), including, in the first place, non-specific hemosorption, plasmapheresis and quantum medicine methods for allergic and immune diseases. For the first time in Russia, the Center forced into application the planned preventive use of ECTM in patients with allergosis. Also, the effectiveness of the low-volume intervention is under study.
The establishment of our laboratory was prompted by a high level of incidence of infectious/inflammatory diseases in all age groups, by the frequent transition from acute to chronic inflammation resulting from non-completion of the immune response, by growing incidence of diseases associated with the deficiency and dysfunction of the immune system. It has already become evident that development of many diseases relies on disorders (inefficiency, inadequacy, and imbalance) of the immune system. Secondary immunodeficiency stems, on the one hand, from multiple harmful effects of the environment, and, on the other hand, from the presence of polymorphisms in genes important for the immune response and inflammation (there are hundreds and thousands of these genes; just apoptotic process alone involves more than 400 genes). The complex organization of the immune system, dynamism of its functioning, variety of defensive functions that are responsible for recognizing and destroying foreign agents, for providing resistance to tumors, and for maintaining integrity of the immune system and stability of the body’s internal milieu, — all of these necessitates comprehensive studies in this field. The studies should base on results of basic research relating to clinical realities, to specific syndromes and diseases. In addition, clinical research should consider that the immune system functions in close collaboration with many organs and other systems (nervous system, endocrine system, etc.). Also, the investigation of the immune system must take into account its non-immune functions such as its participation in the hemopoiesis, reparation processes, regulation of the endocrine system functions and brain cognitive functions, etc.

The main interest of our laboratory is centered on the pathogenic mechanisms for producing a secondary immunodeficiency state, and on search for new, advanced methods for diagnostics and treatment of immune-mediated diseases, immune-related diseases, allergic disorders, and immune disorders.
In recent years, a special attention is given to the investigation of immunodeficiencies caused by viruses. A number of top-priority studies are devoted to chronic fatigue syndrome, non-invasive methods for selecting drug therapy and diagnosing drug allergy.

The major research lines in the laboratory of clinical immunology

  • Multiparametric investigation, at cellular, molecular and systems levels, of pathogenesis of different types of secondary immunodeficiency which underlies chronic infectious-inflammatory diseases and autoimmune pathology, socially important diseases among them.
  • Investigation of effects of new recombinant peptides, among them cytokines, and their combined influence on the immune system upon deficiency of the factors of innate and adaptative immunity.
  • Development of new approaches and principles of immunotherapy during different types of secondary immunodeficiencies to create a platform for personal immunotherapy and immunorestoration.
  • Investigation of the role and causative-consecutive relations of herpes virus infections (cytomegalovirus(CMV), Epstein-Barr virus (EBV), Human herpes virus 6 (HHV-6), Human herpes virus 7 (HHV-7)) and a number of other infections in the development and chronization of immmnodeficiecy states and autoimmune diseases.
  • Development of methods of complex immunotherapy of chronic herpes infections, in particular in the case of infection resistance to abnormal nucleotides.
  • Development of methods for treating virus-induced autoimmune pathology at early stages through immunorestoration, extracorporeal reprogramming of the key factors of antiviral defence.
  • Investigation of and search for new approaches to the evaluation of state of cells of the innate and adaptive immunity by investigating of: the anti-activation markers, the balance and the reserve capacity of cytokine system, cytokine antagonists and cytokine-associated proteins, etc.

At the present time, it is observed the increase in the number of patients with secondary immunodeficiency associated with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/MEM). The recent research in the field of genetics demonstrated the existence of links between certain polymorphisms of the examined genes and the presence of CFS, between the expression of a number of genes and the development of CFS following acute mononucleosis (Rajeevan MS et all. 2007; Lin E, Hsu SY, 2009), which approves the independence of CFS as a nosological entity. The World Health Organization (WHO) considers MEM/CFS as a neurological disorder associated with a dysfunction of the immune system (neuro-immune disease). MEM/CFS is a disease with the unknown etiology and pathogenesis, which is classified as a postviral fatigue syndrome. According to the results of N.A. Didkovsky and his colleagues, the occurrence of patients with MEM/CFS among patients with secondary immunodeficiency and chronic herpes infection is higher than 15%. The major focus of our research in this line is on the etiology and pathogenesis of MEM/CFS and the development of its diagnostics and therapy.

In addition to this key objective, our laboratory is pursuing the following lines of research

Investigation of the influence of low-temperature plasma radiation and other types of radiation on cells of the immune system and on immune-associated cells. Examination of issues on (1) the variability of the responses of factors of immunity on radiation effect, and (2) the evaluation of personal susceptibility, for the purpose of developing approaches and biotechlological methods for this evaluation. Members of the laboratory have a long-term unique experience in large-scale examination of patients, in treating and observing in the dynamics more than 9000 patients with secondary immunodeficiency and various immune dysfunctions pathogenetically associated with various somatic diseases as well as associated with viral and bacterial infections. These are patients with chronic infectious/inflammatory diseases of respiratory and gastrointestinal tracts (bronchial asthma, chronic obstructive pulmonary disease, irritable bowel syndrome, etc.), of ear, nose and throat organs, of urogenital system, and of skin. We also had a deal with more than 150 patients with CFS/MEM.

People

Malashenkova I.K., - Senior Researcher, Ph.D
Komov Vladimir Viktorovich - Senior Researcher, Ph.D
Treskunov V.K. - Senior Researcher, Ph.D
Jarova Maria Alievna - Researcher, Ph.D
Gurskaya Olga Gennadievna - Researcher, Ph.D
Zuikov Igor Aleksandrovich - Researcher, Ph.D
Kompaneez Irina Aleksandrovna - Researcher, Ph.D
Sarsania J. Sh - Researcher, Ph.D
Praslova Elena Igorevna – Junior Researcher
Ogurtsov Daniil - graduate student
Sergey Krynskiy - clinical intern

Dissertations

Jarova Maria Alievna. Characteristics of the immune status of patients with secondary immunodeficiency associated with EBV-infection and the extent of viral load. 2003.
Levko Anatoliy Anatolievich. Personalised approach to immunomodulation therapy in the treatment of chronic relapsing prostatitis caused by urogenital infection. 2005.
Tanasova Anna Nikolaevna. The effectiveness of interferon alpha and cycloferon, an interferon alpha inductor, in the treatment of anogenital and labial herpes infection. 2007.
Hitrik Nadezhda Markovna. Functional characteristics of phagocytes in patients with infection caused by HHV. 2007.
Zenohov Sergey Aleksandrovich. Early diagnostics and treatment of chronic rhinosinusitis in patients with aspirin intolerance. 2007.
Zuikov Igor Aleksandrovich. The cytokine status in patients with secondary immunodeficiency associated with severe HHV infection. 2007.
Gurskaya Olga Gennadievna. The abnormalities of antiviral immunity and disturbance of pro-and anti-inflammatory cytokine balance in patients with chronic fatigue syndrome and immune dysfunction. 2012.

Monographs

Didkivsky N.A. α-1 antitrypsin deficiency. Chapter 9 in Monography Chronic pulmonary diseases in children, edited by Rosinova N.N. and Miseritsky M.> “Practice”, 2011, p. 124-129. ISBN, 978-89816-106-4.
Malashenkova I.K., Didkovsky N.A. On immudomodulating therapy in repiratory diseases. In Rational pharmacotherapy of respiratory diseases. EDITED BY Chuchalin A.G. Moscow, “Littera”, 2012, p. 531-559.

Primary Publications

Didkovsky N.A., Karaulov A.V., Malashenkova I.K. (2000). Chronic fatigue syndrome. Progress in clinical immunology and allergology. Moscow, p. 72-83.
Didkovsky N.A., Govorun V.M., Malashenkova I.K. (2000). The role of Epstein-Barr virus in chronic fatigue syndrome and in immune disfunctions. International Journal on Immunorehabilitation,.-N 1.-С.102-110.
Malashenkova I.K. et al. A Guide for Clinicians Clinical manifestations of chronic Epstein-Barr virus infection. M., 2000, p. 32-35.
Malashenkova I.K., Didkovsky N.A., Sarsania J.S., Jarova M.A., Schepetkovs I.N., Chistova L.A., Pichujkina O.V., Guseva T.S., Parshina O.V. Clinical manifestations of chronic Epstein-Barr virus infection: diagnostics and treatment. The Medical Practitioner, №9, 2003, p. 32-38.
Didkovsky N.A., Dvoretskiy L.I., Zenohov S.A. Theangioneurotic oedema. Principles of diagnostics and therapy. Russian Medical Journal, 12, №18, 2004< p. 1067-1075. Malashenkova I.K., Didkovsky N.A., Levko A.A. On personalised approach to immunomodulating therapy. Pharmateca, 2004, p. 118-122. Didkovsky N.A., Jarova M.A. Hereditary factors in respiratory diseases. Pulmonology, №4, 2005, p. 11-17. Sokolova T.M, Ershov F.I., Didkovsky N.A. et al. Individual changes in expression of the interferon system genes in human blood cells in response to amiksin and cyclopheron. Issues of Virogy. №2, 2005, p. 32-35. Didkovsky N.A., Jarova M.A. Primary pulmonary emphysema. Ther. Archive, №12, 2005, P. 67-70. Didkovsky N.A., Malashenkova I.K., Sarsnia J.S., et al. Aspects of pathogenesis of severe infection caused by HHV. The Bulletin of experimental biology and medicine. 2007. P. 76-81. Didkovsky N.A., Komov V.V., Malashenkova I.K., et al. Approaches to personalization of quantum haemotherapy protocols. Haemopheresis ans quantum therapy in clinical medicine. – M., 2008. P. 125. Didkovsky N.A. et al. The use of argon plasma to modulate peripheral blood phagocyte and lymphocyte function in secondary immunodeficiency patients with infected wounds and ulcers. Efferent and physic-chemical medicine №2, 2010, 62-66. Didkovsky N.A. et al. Pro-inflammatory and anti-inflammatory cytokines levels in chronic fatigue syndrome assotiated with herpesvirus infection. Russian Allergological Journal. – 2011. - №4, 1. – P. 214-216. Didkovsky N.A. et al. Effects of sorbtion and laser impact on blood chemoluminescence (results of an imitating experimental research). Russian Allergological Journal. 2011, - №4, 1. – p. 104-106. Didkovsky N.A. et al. Il-8 and IFN levels in chronic fatigue syndrome assotiated with herpesvirus infection and immune dysfunction. Medical Immunology. – 2011. - №4-5, 13. P. 485-486. Didkovsky N.A., Jarova M.A., Kablashova N.A. A case of multiple genetic aberrations in several pulmonary protective mechanisms. PULMONOLOGY, 2011, №1, P. 69-73. Malashenkova I.K., Gurskaya O.G., Zuikov I.A., Didkovsky N.A. The role of lymphotropic viruses in pathogenesis of chronic fatigue syndrome assotiated with immune dysfunction. Russian Allergological Journal. – 2012. - №1. – 1. – P. 193-195. Malashenkova I.K., Jarova M.A., Didkovsky N.A. Approaches to diagnosing secondary immune dysfunction associated with herpesvirus infection in chronic infectious diseases and in chronic fatigue syndrome. Efferent and physic-chemical medicine – 2012, №4, p. 24-38. Malashenkova I.K., Gurskaya O.G., Didkovsky N.A., et al. Human herpesvirus 7 in the pathogenesis of chronic fatigue syndrome. Russian Allergological Journal. – 2012, №5, 1, p. 193-195. Didkovsky N.A., Malashenkova I.K., Ogurtsov D.P. The putative role of IL-15 in cerebral pathology in myalgic encephalomyelitis/chronic fatigue syndrome. Russian Allergological Journal, 2013, №2 p. 82-83.