MAJOR LYMPHOCYTE SUBPOPULATIONS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND THEIR ASSOCIATIONS WITH CELLULAR AND HUMORAL ANTI-ENDOTOXIN IMMUNITY

At the present time, systemic lupus erythematosus (SLE) takes the leading place among systemic autoimmune disorders. Despite considerable progress in understanding basic pathogenesis of this disease, many subtle mechanisms of progressive inflammation in SLE are still unknown. It has been discovered that the persistent self-maintenance factors of autoimmune inflammation could be represented by lipopolysaccharides or endotoxins of Gram-negative intestinal bacteria. The objective of this study was to assess the levels of major lymphocyte subpopulations, and their probable relation to specific anti-endotoxin antibodies and endotoxin-neutralizing receptors of granulocytes and monocytes in peripheral blood of SLE patients. The study involved forty-eight patients with SLE. The levels of lymphocyte subpopulations, expression of monocyte and granulocyte anti-endotoxin receptors, amounts of total and endotoxin-specific immunoglobulins were determined by means of, respectively, cytometric analysis and enzyme immunoassay techniques. The results of study have shown an increase in overall numbers of activated and cytotoxic T lymphocytes, a decrease in lymphocytes and NK-cells, diminished levels endotoxin-binding receptors on the monocytes and granulocytes, along with increased anti-endotoxin IgG antibodies. Our study revealed correlations between the levels of the leukocyte endotoxin-binding receptors, and B-lymphocyte contents, like as some associations between anti-endotoxin IgM antibodies, and the levels of B-lymphocytes, and cytotoxic T-lymphocytes. A correlation was also found between anti-endotoxin IgG antibodies and CD4+ lymphocyte levels. Significant alterations of the endotoxin-specific immunity among SLE patients suggest that this imbalance might play an important role in the mechanisms of onset and progression of autoimmune diseases.

1. Гордиенко А.И. Улучшенный метод получения флуоресцентного зонда для определения липополи-сахарид-связывающих рецепторов методом проточной лазерной цитофлуориметрии // Таврический медико-биологический вестник, 2007. Т. 10. №4. С. 156-160. [Gordienko A.I. Improved method for producing a fluorescent probe to determine the lipopolysaccharide-binding receptors by flow cytometry laser. Tavricheskiy mediko-biologicheskiy vestnik = Tavricheskiy Mediko-Biologicheskiy Vestnik, 2007, Vol. 10, no. 4, pp. 156-160. (In Russ.)]

2. Гордиенко А.И., Копаенко А.И., Бакова А.А., Химич Н.В.. Влияние комплексного лечения с применением пробиотиков и энтеросорбентов на эндотоксин-связывающий потенциал лейкоцитов и эндогенную интоксикацию у пациентов с передним увеитом, ассоциированным с HLA-B27 антигеном // Таврический медико-биологический вестник, 2012. Т. 15, №2, ч. 3 (58). С. 75-78. [Gordienko A.I., Kopayenko А.I., Bakova A.A., Khimich N.V. Influencing of complex treatment with probioticsand enterosorbents on endotoxin- binding capacity of leucocytesand endogenous intoxication in patients with HLA-B27 associated anterior uveitis. Tavricheskiy mediko-biologicheskiy vestnik = Tavricheskiy Mediko-Biologicheskiy Vestnik, 2012, Vol. 15, no. 2 (58), pp. 75-78. (In Russ.)]

3. Клюквина Н.Г., Насонов Е.Л. Фармакотерапия системной красной волчанки: современные рекомендации // Русский медицинский журнал, 2010. Т.18, № 18. С. 1108-1113. [Klykvina N.G. Nasonov E.L. Pharmacotherapy of systemic lupus erythematosus: current recommendations. Russkiy meditsinskiy zhurnal = Russian Medical Journal, 2010, Vol. 18, no. 18, pp. 1108-1113. (In Russ.)]

4. Кравченко П.Н., Олейник Е.К. Система регуляторных Т-клеток и аутоиммунные процессы // Труды Карельского научного центра РАН, 2013. № 3. С. 18-30. [Kravchenko P.N., Oleinik E.K. The system of regulatory t cells and autoimmunity. Trudy Karel`skogo nauchnogo tsentra RAN = Transactions of Karelian Research Centre of RAS, 2013, no. 3, pp.18-30. (In Russ.)]

5. Романова Н.В. Полисиндромность системной красной волчанки и фенотип лимфоцитов // Фундаментальные исследования, 2004. № 2. С. 92-93. [Romanova N.V. Polysyndromic of systemic lupus erythematosus and lymphocyte phenotype. Fundamental`nye issledovaniya = Fundamental Research, 2004, no. 2., pp. 92-93. (In Russ.)]

6. Савенкова В.В., Солошенко Е.М., Білозоров О.П. Характеристика імунного статусу хворих на хронічний червоний вовчак залежно від стадії захворювання // Дерматология та венерология, 2013. № 3 (61). С. 77-83. [Savenkova V.V., Soloshenkо E.M., Bilozorov O.P. Characteristics of immune status of patients with chronic lupus erythematosus depending on the stage of disease. Dermatologiya ta venerologiya = Dermatology and Venereology, 2013, no. 3 (61), pp. 77-83. (In Russ.)]

7. Bucala R. Polyclonal activation of B lymphocytes by lipopolysaccharide requires macrophage-derived interleukin-1. Immunology, 1992, Vol. 77, no. 4, pp. 477-482.

8. Fan H., Liu F., Dong G., Ren D., Xu Y., Dou J., Wang T., Sun L., Hou Y. Activation-induced necroptosis contributes to B-cell lymphopenia in active systemic lupus erythematosus. Cell. Death. Dis., 2014, Vol. 5, no. 9, p. 375.

9. Gao N., Dresel J., Eckstein V., Gallert R., Störch H., Venigalla R.K.C., Schwenger V., Max R., Blank N., Lorenz H-M., Tretter T. Impaired suppressive capacity of activation-induced regulatory B cells in systemic lupus erythematosus. Arthritis Rheumatol., 2014, Vol. 66, no. 10, pp. 2849-2861.

10. Granholm N.A., Cavallo T. Long-lasting effects of bacterial lipopolysaccharide promote progression of lupus nephritis in NZB/W mice. Lupus, 1994, Vol. 3, no. 6, pp. 507-514.

11. Hu S., Tao D., He P. Immunophenotyping of lymphocyte T and B in the peripheral blood of systemic lupus erythematosus. J. Tongji. Med. Univ., 2001, Vol. 21, no. 2, pp. 108-109.

12. Kammer G.M., Perl A., Richardson B.C., Tsokos G.C. Abnormal T cell signal transduction in systemic lupus erythematosus. Arthritis Rheum., 2002, Vol. 46, no. 5, pp. 1139-1154.

13. Mak A., Cheung M.W., Chiew H.J., Liu Y. Global trend of survival and damage of systemic lupus erythematosus: metaanalysis and metaregression of observational studies from the 1950 to 2000. Semin. Arthr. Rheum., 2012, Vol. 41, pp. 830-839.

14. Mattern T., Flad H-D., Brade L., Rietschel E.T., Ulmer A.J. Stimulation of human T-lymphocytes by LPS is MHC unrestricted but strongly dependent on B7 interaction. Immunology, 1998, Vol. 160, pp. 3412-3418.

15. Novak J., Lehuen A. Mechanism of regulation of autoimmunity by iNKT cells. Cytokine, 2011, Vol. 53, pp. 263-270.

16. Odendahl M., Jacobi A., Hansen A., Feist E., Hiepe F., Burmester G.R., Lipsky P.E., Radbruch A., Dörner T. Disturbed peripheral B lymphocyte homeostasis in systemic lupus erythematosus. J. Immunol., 2000, Vol. 165, no. 10, pp. 5970-5979.

17. Sabry A., Sheashaa H., El-Husseini A., Mahmouda K., Eldahshana K.F., Georgea S.K., Abdel-Khaleka E., El-Shafeyb E.M., Abo-Zenahc H. Proinflammatory cytokines (TNF-alpha and IL-6 in Egyptian patients with SLE: Its correlation with disease activity. Cytokine, 2006, Vol. 4, pp. 722-727.