IDENTIFICATION OF ANTIGEN-SPECIFIC HORMONE-RESISTANT BLOOD LYMPHOCYTES TO PREDICT EFFICIENCY OF GLUCOCORTICOID THERAPY IN BRONCHIAL ASTHMA

Abstract. At present time, the main therapeutic goal in bronchial asthma treatment is to achieve complete control of the disease. Appropriate medical evaluation involves  a  complex  system  of  clinical  criteria  and functional  parameters  obtained  by  instrumental  and laboratory  techniques.  Wide  application  of  inhalatory glucocorticosteroids (IGCS) in childhood bronchial asthma treatment, requirements for a long-term therapy, and common IGCS dose-escalation regimens determine an importance of searching novel objective criteria to  predict  efficiency  of  the  therapy  preformed.  In  present  work,  we  propose  a  method  aimed  to  identify glucocorticosteroid-resistant lymphocytes in peripheral blood of the patients with bronchial asthma undergoing IGCS therapy. The results of this study have shown that clinical efficiency of such treatment of bronchial asthma patients, independently on the IGCS dosage, may be evaluated by the degree of steroid-induced suppression of in vitro lymphocyte proliferation caused by a domestic dust antigen. The data obtained may be used in clinical settings to predict efficiency of IGCS therapy and adjust treatment regimens in bronchial asthma patients. (Med. Immunol., 2011, vol. 13, N 2-3, pp 157-166)

1. Баранов А.А., Балаболкин И.И., Боровик Т.Э. Детская аллергология: руководство для врачей. – М.: ГЭОТАР-Медиа, 2006. – 688 с

2. Воробьев А.А. Быков А.С., Караулов А.В. Иммунология и аллергология. – M.: Практическая медицина. – 2006. – 282 с

3. Найт С. Анализ пролиферации лимфоцитов // Лимфоциты. Методы: Пер. с англ. / Под. ред. Дж. Клауса. – М.: Мир, 1990. – С. 286-310

4. Федосеев Г.Б., Трофимов В.И. Бронхиальная астма. – СПб.: Нордмедиздат, 2006. – 308 с.

5. Adcock I.M., Barnes P.J. Molecular mechanisms of corticosteroid resistance // Chest. – 2008. – Vol. 134, N 2. – P. 394-401.

6. Anandan C., Nurmatov U., van Schayck O.C.P., Sheikh A. Is the prevalence of asthma declining? Systematic review of epidemiological studies // Allergy. – 2010. – Vol. 65. – P. 152-167.

7. Azzolina L.S., Stevanoni G., Tridente G. DNA analysis of stimulated lymphocytes by automatic sampling for flow cytometry // Cytometry. – 1988. – Vol. 9. – P. 508-511.

8. Barnes P.J., Chung K.F., Page C.P. Inflammatory mediators of asthma: an update // Pharmacol. Rev. – 1998. – Vol. 50, N 4. – P. 515-596.

9. Bellinghausen I., Klostermann B., Knop J., Saloga J. Human CD4+CD25+ T cells derived from the majority of atopic donors are able to suppress TH1 and TH2 cytokine production // J. Allergy Clin Immunol. – 2003. – Vol. 111. – P. 862-868.

10. Bloemena E., Roos M.T., Van Heijst J.L., Vossen J.M., Schellekens P.T. Whole-blood lymphocyte cultures // J. Immunol. Methods. – 1989. – Vol. 122, N 2. – P. 161-167.

11. Bussa S. Rumi C., Leone G., Bizzi B. Evaluation of a new whole blood cytometric lymphocyte transformation test for immunological screening // J. Clin. Lab. Immunol. – 1993. – Vol. 40. – P. 39-46.

12. Crissman H.A., Steincamp J.A. Multivariate cell analysis: Techniques for correlated measurements of DNA and other cellular constituents // Techniques in cell cycle analysis. – Clifton, New-Jersey: Humana Press.Inc., 1987. – P. 163-206.

13. Du J., Li M., Zhang D., Zhu X., Zhang W., Gi W., Feng Y., Zhai X., Ling Ch. Flow cytometry analysis of glucocorticoid receptor expression and binding in steroid-sensitive and steroid-resistant patients with systemic lupus erythematosus // Arthritis Res. Ther. – 2009. – Vol. 11, N 4. – P. 108-116. 14. Global Initiative for Asthma.-NHLB/WHO Workshop Report. – National Heart Lung Blood Institute, 2009. – 112 P.

14. Grindebacke H., Wing K., Andersson A.-C., Suri-Payer E., Rak S., Rudin A. Defective suppression of Th2 cytokines by CD4CD25 regulatory T cells in birch allergics during birch pollen season // Clin. Exp. Allergy. – 2004. – Vol. 34. – P. 1364-1372.

15. Haczku A., Alexander A., Brown P., Assoufi B., Li B., Kay A.B. and Corrigan C. The effect of dexamethasone, cyclosporine, and rapamycin on T-lymphocyte proliferation in vitro: Comparison of cells from patients with glucocorticoid-sensitive and glucocorticoid-resistant chronic asthma // J. Allergy Clin. Immunol. – 1994. – Vol. 93. – P. 510-519.

16. John M., Lim S., Seybold J., Jose P, Robichaud A., O’Connor B., Barnes P.J., Chung K.F. Inhaled corticosteroids increase interleukin-10 but reduce macrophage inflammatory protein-1a, granulocyte-macrophage stimulating factor and interferon-g release from alveolar macrophages in asthma // Am. J. Respir. Crit. Care Med. – 1998. – Vol. 157. – P. 256-262.

17. Karagiannidis C, Akdis M, Holopainen P. Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma // J. Allergy Clin. Immunol. – 2004. – Vol. 114. – P. 1425-1433.

18. Kohler Ch., Kolopp-Sarda M.N., De March-Kennel A. Sequential assessment of cell cycle S phase in flow cytometry: a non-isotopic method to measure lymphocyte activation in vitro // Analytical Cellular Pathology – 1997. – Vol. 14. – P. 51-59.

19. Lee J.-H., Yu H.-H., Wang L.-C., Lin Y.-T., Chiang B.-L. The levels of CD4+CD25+ regulatory T cells in paediatric patients with allergic rhinitis and bronchial asthma // Clin. Exp. Immunol. – 2007. – Vol. 148, N 1. – P. 53-63.

20. Li M., Song L., Zhang J.B., Fang J., Li L. Changes of CD4+CD25+ regulatory T cells, IL-10 and TGF-beta 1 levels in peripheral blood in children with asthma // Zhongguo Dang Dai Er Ke Za Zhi. – 2009. – Vol. 11, N 10. – P. 829-832.

21. Moore K.W., de Waal Malefyt R., Coffman R.L., O’Garra A. Interleukin-10 and the interleukin-10 receptor // Annu Rev. Immunol. – 2001. – Vol. 19. – P. 683-765.

22. Ormerod M.G., Tribukait B., Giaretti W. Consensus report of the task force on standardization of DNA flow cytometry in clinical pathology // Anal.Cell Pathol. – 1998. – Vol. 17, N 2. – P. 103-110.

23. Peek E.J., Richards D.F., Faith A., Lavender P. Interleukin-10-Secreting ”regulatory” T cells induced by glucocorticoids and β2-agonists. // Am. J. Respir. Cell and Molecular biology. – 2005. – Vol. 33. – P.105-111.

24. Report of the commetee on clinical immunology of the IUIS // Eur. J. Immunol. – 1976. – Vol. 6. – P. 231-234.

25. Shankey T.V., Rabinovitch P.S., Bagwell B., Bauer K.D., Duque R.E., Hedley D.W., Mayall B.H., Wheeless L. Guidelines for implementation of clinical DNA cytometry // Cytometry – 1993. – Vol. 14. – P. 472-477.

26. Shi H.Z., Li S., Xie Z.F., Oin X.J., Oin X., Zhong X.N. Regulatory CD4+CD25+ T lymphocytes in peripheral blood from patients with atopic asthma // Clin. Immunol. – 2004. – Vol. 113. – P. 172-178.

27. Till S.J., Durham S.R., Rajakulasingam K. Allergen-induced proliferation and interleukin-5 production by bronchoalveolar lavage and blood T cells after segmental allergen challenge // Am. J. Respir. Crit. Care Med. – 1998. – Vol. 158, N 2. – P. 404-411.