Detecção de determinantes antigênicos compartilhados entre a proteína de choque térmico 65 do Mycobacterium leprae e proteína de choque térmico 60 humana

David Njoo; Ricardo.V.P. Hu; Bhupendra Tank; Arend.H.J. Kolk; Angela Kooy; René Kant; Bernard Naafs

doi:10.47878/hi.2003.v28.35297

Autores

David Njoo MD, PhD, Department of Dermatology and Venereology, Dijkzigt Hospital, Erasmus University Rotterdam, The Netherlands. Department of Dermatology and Venereology, Academic Medical Centre University of Amsterdam, The Netherlands
Ricardo.V.P. Hu MD, Dermatovenereologist, Department of Dermatology and Venereology, Dijkzigt Hospital, Erasmus University Rotterdam, The Netherlands. Department of Dermatology and Venereology, Academic Hospital Paramaribo, Surinam
Bhupendra Tank PhD, Department of Dermatology and Venereology, Dijkzigt Hospital, Erasmus University Rotterdam, The Netherlands.
Arend.H.J. Kolk PhD, N.H. Swellengrebel Laboratory of Tropical Hygiene, Royal Tropical Institute, Amsterdam, The Netherlands
Angela Kooy PhD, N.H. Swellengrebel Laboratory of Tropical Hygiene, Royal Tropical Institute, Amsterdam, The Netherlands
René Kant MT, Department of Dermatology and Venereology, Dijkzigt Hospital, Erasmus University Rotterdam, The Netherlands.
Bernard Naafs M.D, Ph.D, Dermatovenereologist, Department of Dermatology and Venereology, Dijkzigt Hospital, Erasmus University Rotterdam, The Netherlands. Department of Dermatology and Venereology, Academic Hospital Leiden, The Netherlands. Instituto Lauro de Souza Lima, Bauru,SP, Brasil

DOI:

https://doi.org/10.47878/hi.2003.v28.35297

Palavras-chave:

hanseníase, doenças granulomatosas, autoimunidade, proteínas de choque térmico, HSP-60, HSP-65, imunopatologia, Western blot

Resumo

Nestes estudos foram investigados se o Mycobacterium leprae (M. leprae) e o homem compartilham determinantes antigênicos que podem estar localizados nas Proteínas de Choque Térmico (HSPs) e que podem ser responsáveis pela destruição tecidual. Usando-se técnica de coloração única pela imunoperoxidase em cortes feitos com criostato, observaram-se três anticorpos que eram dirigidos contra HSP-60 (anticorpos policlonais SPA-804, SPA-805 e o anticorpo monoclonal SPA-807), que provavelmente reagiam especificamente com macrófagos e células epitelióides em biópsias cutâneas de pacientes com hanseníase. No Western Blot foi observado que todos os anticorpos contra HSP-60 humana e anticorpos monoclonais (MoAbs) contra HSP-65 do M. leprae (F47-10, F67-18, F88-1) reagiam intensamente com as proteínas do M. leprae sonicado com peso molecular de 65 kDa, indicando semelhança de alguns determinantes antigênicos entre HSP-60 humana e HSP-65 do M. leprae. Subseqüentemente, um estudo imunoistoquímico comparativo dos padrões de coloração de anticorpos contra HSP-60 humana e anticorpos contra HSP-65 do M. leprae, usando cortes cutâneos feito em criostato de hanseníase paucibacilar (PB), multibacilar (MB) e outras doenças granulomatosas, revelaram que os MoAbs F47-10 e F67-18 reagiam somente fracamente com os granulomas em hanseníase PB e em outras doenças granulomatosas cutâneas, mas coravam o granuloma da hanseníase MB intensamente. O MoAb F88-1 e os anticorpos policlonais SPA-804, SPA-805 e o MoAb SPA807 coraram os granulomas dos pacientes PB e de outras doenças cutâneas granulomatosas com a mesmaintensidade daquela nos pacientes MB. Utilizando-se uma técnica de dupla coloração, observou-se que os determinantes antigênicos reconhecidos pelo MoAb contra HSP-60 humana (SPA-807) e os MoAbs contra a HSP-65 do M. leprae (F67-18, F47-10, F88-1) estavam, na maioria das vezes, localizados nos macrófagos. Esses achados não contradizem nossa hipótese de que semelhanças entre determinantes antigênicos nas HSPs no M. leprae e no hospedeiro humano podem ser, no mínimo em parte, responsáveis pela indução de uma reação autoimune na hanseníase causando formação de granuloma com subseqüente dano tecidual. Os resultados deste estudo também indicaram que alguns destes determinantes estão provavelmente localizados na HSP-60. Uma explicação similar possivelmente se aplique aos achados em outras doenças granulomatosas, como por exemplo, na sarcoidose provavelmente induzida por micobactéria, e na necrobiose lipoídica relacionada ao diabete, nas quais considera-se que epítopos semelhantes existam entre a HSP-65 bacteriana e a HSP-60 humana e desempenhem um papel importante.

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