IMMUNOLOGICAL FEATURES OF ALLERGIC AND NON-ALLERGIC FORMS OF ATOPIC DERMATITIS

Abstract. In spite of similar clinical patterns, there are numerous differences in immunopathogenesis of intrinsiс and extrinsiс forms of atopic dermatitis. Patients with both forms have decreased levels of CD8+CD25+ lymphocytes, decreased telomere DNA length of CD4+T-cells, decreased migration inhibition index in delayedtype hypersensitivity, decreased levels of CD16+NK-cells, decreased Fc-dependent monocyte and granulocyte phagocytosis, increased hydrogen peroxide production by neutrophils, increased levels of CD19+B-cells, as well as high IgA and IgG immunoglobulin levels. Extrinsiс form of atopic dermatitis are characterized by more severe clinical course, and by involvement of both immediate hypersensitivity (hyperproduction of IgE and decreased T-cells with intracellular IFNγ production), like as delayed-type hypersensitivity (decreased migration index along with decreased migration inhibition index). CD8+ play a large role in extrinsiс form of atopic dermatitis that may be traced as decreased telomere length of CD8+T- cells, decreased levels of CD8+CD45RO+ cells, increased levels of CD8+CD45RA+ naive cells and increased levels of CD28+ costimulatory molecules on CD8+cells. Increased levels of CD4+CD25+bright cells and strongly alterations of innate immunity determined of decreased H2O2 production by monocytes are shown in extrinsiс form. Hence, the severity index of atopic dermatitis is more expressed in extrinsic form of bronchial asthma and it is, probably, determined by more exaggerated immunological alterations.

1. Борисов В.И. Укорочение длины теломерных районов ДНК при иммунодефицитных, аллергических и аутоиммунных состояниях // Автореф. дис. ...канд. мед. наук. – Новосибирск, 2007.

2. Донецкова А.Д., Шарова Н.И., Литвина М.М., Бурменская О.В., Трофимов Д.Ю., Ярцев М.Н., Алексеев Л.П., Ярилин А.А. Регуляторные Т-клетки при аллергии у детей // Медицинская иммунология. – 2008. – Т. 10, № 2-3. – С. 159- 166.

3. Кожевников В.С. и др. Оценка иммуномодулирующего эффекта терапии с применением эритропоэтина у больных ревматоидным артритом // Медицинская иммунология. – 2004. – Т. 6, № 6. – С. 557-563.

4. Лозовой В.П., Кожевников В.С. Методические рекомендации МЗ СССР. – Новосибирск, 1990. – 11 с.

5. Сергеев Ю.В. Иммунные механизмы патогенеза и обоснование дифференцированных подходов к иммунокорригирующему лечению и профилактике атопического дерматита // Автореф. дисс. ...докт. мед. наук. – М., 1990.

6. Akdis C.A., Akdis M., Simon D., Dibbert B., Weber M., Gratzl S., Kreyden O., Disch R., Wuthrich B., Blaser K., Simon H. T-Cells and T-Cell- Derived Cytokines as Pathogenic Factors in the Nonallergic Form of Atopic Dermatitis // J. Invest. Dermatol. – 1999. – Vol. 113. – P. 628- 634.

7. Akdis M., Akdis C.A., Weigl L., Disch R., Blaser K. Skin-homing, CLA- memory T-cells are activated in atopic dermatitis and regulate IgE by an IL-13-dominated cytokine pattern. IgG4 counterregulation by CLA- memory T-cells // J. Immunol. – 1997. – Vol. 159. – P. 4611-4619.

8. Akdis M., Simon H.-U., Weigl L., Kreyden O., Blaser K., and Akdis C.A. Skin homing (cutaneous lymphocyte-associated antigen-positive) CD8 T-cells respond to superantigen and contribute to eosinophilia and IgE production in atopic dermatitis // J. Immunol. – 1999. – Vol. 163 – P. 466-475.

9. Akdis M., Trautmann A., Klunker S., Daigle I., Kucuksezer U.C., Deglmann W., Disch R., Blaser K., Akdis C.A. T-helper (Th) 2 predominance in atopic diseases is due to preferential apoptosis of circulating memory/effector Th1-cells // FASEB J. – 2003. – Vol. 17. – P. 1026-1035.

10. Aman M.J., Tayebi N., Obiri N.I., Puri R.K., Modi W.S., Leonard W.J. cDNA cloning and characterization of the human interleukin 13 receptor alpha chain // J. Biol. Chem. – 1996. – Vol. 271. – P. 29265-29270.

11. Bacher M., Metz C.N., Calandra T., Mayer K., Chesney J., Lohoff M., Gemsa D., Donnelly T., and Bucala R. An essential regulatory role for macrophage migration inhibitory factor in T-cell activation // Proc. Natl. Acad. Sci. USA. – 1996. – Vol. 93. – P. 7849-7854.

12. Bernhagen J. et al. Purification, bioactivity, and secondary structure analysis of mouse and human macrophage migration inhibitory factor (MIF) // Biochemistry. – 1994. – Vol. 33, N 47. – P. 14144 - 14155.

13. Bieber T., Delespesse G. gamma-interferon promotes the release of IgE-binding factors (soluble CD23) by human epidermal Langerhans cells // J. Invest. Dermatol. – 1991. – Vol. 97. – P. 600-603.

14. Flores-Romo L., Cairns J.A., Millsum M.J., Gordon J. Soluble fragments of the low-affinity IgE receptor (CD23) inhibit the spontaneous migration of U937 monocytic cells: neutralization of MIF activity by a CD23 antibody // Immunology. – 1989. – Vol. 67. – P. 547-549.

15. Galli S.J., Nakae S., and Tsai M. Mast cells in the development of adaptive immune responses // Nat. Immunol. – 2005. – Vol. 6. – P. 135-142.

16. Hennino A., Vocanson M., Toussaint Y., Rodet K., Benetière J., Schmit A., Aries M., Bérard F., Rozières A., Nicolas J. Skin-Infiltrating CD8+ T Cells Initiate Atopic Dermatitis Lesions. // J. Immunol. – 2007. – Vol. 178. – P. 5571-5577.

17. Hofer M., Jirapongsananuruk O., Trumble A., Leung D. Upregulation of B 7.2, but not B7.1, on B-cells from patients with allergic asthma // J. Allergy Clin. Immunol. – 1998. – Vol. 101. – P. 96 - 102.

18. Howell M.D., Novak N., Bieber T., Pastore S., Girolomoni G., Boguniewicz M., Streib J., Wong C., Gallo R.L., Leung D.Y.M. Interleukin-10 downregulates anti-microbial peptide expression in atopic dermatitis // J. Invest. Dermatol. – 2005. – Vol. 125. – P. 738-745.

19. Jirapongsananuruk O., Hofer M., Trumble A., Norris D., Leung D. Enhanced expression of B7.2 (CD86) in patients with atopic dermatitis: a potential role in the modulation of IgE synthesis // J. Immunol. – 1998. – Vol. 160. – P. 4622-4627.

20. Kerschenlohr K., Decard S., Darsow U., Ollert M., Wollenberg A. Clinical and immunologic reactivity to aeroallergens in «intrinsic» atopic dermatitis patients // J. Allergy Clin. Immunol. – 2003. – Vol. 111. – P. 195-197.

21. Laske N., Niggemann B. Does the severity of atopic dermatitis correlate with serum IgE levels? // Ped. Allergy Immunol. – 2004. – Vol. 15, N 1. – P. 86-88.

22. Leung D.Y.M., Boguniewicz M., Howell M.D., Nomura I., Hamid Q.A. New insights into atopic dermatitis // J. Clin. Invest. – 2004. – Vol. 113, N 5. – P. 651-657.

23. Moreno Gimenez J.C. Atopic dermatitis // Alergol Inmunol Clin. – 2000. – Vol. 1. – P. 279 - 295.

24. Nagata N., Oshida T., Yoshida N. L., Yuyama N., Sugita Y., Tsujimoto G., Katsunuma T., Akasawa A., Saito H. Analysis of highly expressed genes in monocytes from atopic dermatitis patients // Int. Arch. Allergy Immunol. – 2003. – Vol. 132, N 2. – P. 156-167.

25. Novak N., Bieber T., Leung D.Y.M. Immune mechanisms leading to atopic dermatitis // J. Allergy Clin. Immunol.– 2003. – Vol. 112. – P. 128-139.

26. Novak N., Kraft S., Bieber T. Unraveling the mission of FceRI on antigenpresenting cells // J. Allergy Clin. Immunol. – 2003. – Vol. 111. – P. 38 - 44.

27. Ou L-S., Goleva E., Hall C., Leung D.Y. T regulatory cells in atopic dermatitis and subversion of their activity by superantigens // J. Allergy Clin. Immunol. – 2004. – 113. P. 756-63.

28. Rocklin R.E., Rosen F.S., David J.R. In vitro lymphocyte response in patients with immunologic disorders: correlation of prediction of macrophage inhibitory factor with delayed hypersensitivity // New Engl. J. Med. – 1970. – Vol. 282. – P. 1340-1343.

29. Rossi A.G., Haslett C., Hirani N., Greening A.P., Rahman I., Metz C.N., Bucala R., and Donnelly S.C. Human circulating eosinophils secrete macrophage migration inhibitory factor (MIF). Potential role in asthma // J. Clin. Invest. – 1998. – Vol. 101. – P. 2869-2874.

30. Salgame P., Abrams J.S., Clayberger C., Goldstein H., Convit J., Modlin R.L., Bloom B.R. Differing lymphokine profiles of functional subsets of human CD4 and CD8 T-cell clones // Science. – 1991. – Vol. 254. – P. 279-282.

31. Santamaria Babi L.F., Picker L.J., Perez Soler M.T., Drzimalla K., Flohr P., Blaser K., and Hauser C. Circulating allergen-reactive T cells from patients with atopic dermatitis and allergic contact dermatitis express the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen // J. Exp. Med. – 1995. – Vol. 181. –P. 1935-1940.

32. Simon D., Borelli S., Braathen L.R., Simon H.- U. Peripheral blood mononuclear cells from IgE- and non-IgEassociated allergic atopic eczema/dermatitis syndrome (AEDS) demonstrate increased capacity of generating interleukin-13 but differ in their potential of synthesizing interferon-γ // Allergy. – 2002. – Vol. 57. – P. 431-435.

33. Teraki Y., Hotta Т., Shiohara Т. Increased circulating skin-homing cutaneous lymphocyteassociated antigen (CLA)+ type 2 cytokine-producing cells, and decreased CLA+ type 1 cytokine-producing cells in atopic dermatitis // Br. J. Dermatol. – 2000. – Vol. 143. – P. 373-378.

34. Trautmann A., Akdis M., Kleemann, Altznauer F., Simon H.U., Graeve T., Noll M., Brocker E.B., Blaser K., Akdis C.A. T cell-mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis // J. Clin. Invest. – 2000. – Vol. 106, N 1. – P. 25-35.

35. Wang B., Huang X., Wolters P.J., Sun J., Kitamoto S., Yang M., Riese R., Leng L., Chapman H.A., Finn P.W., David J.R., Bucala R., Shi G.-P. Deficiency of macrophage migration inhibitory factor impairs murine airway allergic responses // J. Immunol. – 2006. – Vol. 177. – P. 5779-5784.

36. Wehrmann W., Reinhold U., Kukel S., Franke N., Uerloch M., Kreysel H.W. Selective alterations in natural killer cell subsets in patients with atopic dermatitis // Int. Arch. Allergy Appl. Immunol. – 1990. – Vol 92, N 3. – P. 318-22.

37. Weng N., Levine B.L., June C.H., Hodes R.J. Regulated expression of telomerase activity in human T-lymphocyte development and activation // J. Exp. Med. – 1996. – P. 2471-2479.

38. Wu K., Higashi N., Hansen E.R., Lung M., Bang K., Thestrup-Pedersen K. Telomerase activity is increased and telomere length shortened in T-cells from blood of patient with atopic dermatitis and psoriasis // J. Immunol. – 2000. – Vol. 165. –P. 4742 - 4747.

39. Yamashiro M., Okubo Y., Kato Y., Tamaki T., Koga M. The study of immunological markers in patients with «intrinsic» type atopic dermatitis // Japan J. Allergol. – 2002. – Vol. 51, N 7. – P. 552 - 558.