Cellular immune rescue in HIV-Leprosy co-infection during immune reconstitution syndrome (IRIS)
A. Oliveira1, K. Reis2, A. Gomes2, V. Menezes2, J. Nery2, T. Amadeu2, E. Sarno2, R. Pinheiro2
1FIOCRUZ-IOC, Leprosy, Rio de Janeiro, Brazil, 2FIOCRUZ-IOC, Rio de Janeiro, Brazil
Background: Previous results demonstrated that co-infected HIV/leprosy patients on HAART have a higher risk of developing reversal reaction (RR) than non co-infected leprosy patients. HAART treatment can lead to atypical inflammatory diseases (IRIS). This syndrome has been observed in leprosy/HIV co-infection and clinical symptoms are similar to RR although IRIS treatment occurs with a delay in lesions regression. The aim of this study is to evaluate immunological and histopathological profile of co-infected individuals with RR and IRIS in order to understand the differences and mechanisms that lead to these episodes.
Methods: Leprosy co-infected patients were recruited in Souza Araújo Out-Patient Unit at FIOCRUZ. Cytokines in serum were evaluated by ELISA and lymphocyte phenotype by cytometry. Skin biopsies were obtained for immunohistochemistry and RT-PCR.
Results: We observed that RR episodes have local intense inflammatory infiltrate while IRIS patients present an inflammatory infiltrate with some necroses areas. RNAm expression in skin biopsies of RR patients showed a reduction in pro and anti-inflammatory cytokine expression compared with IRIS. In sera we observed an increase in the production of pro-inflammatory cytokines in IRIS patients with an exacerbate production of INF-y when compared to RR patients. Cytometric analysis showed that RR and IRIS patients had an increase CD8+CD45RO+ in response to M. leprae in contrast with RR non co-infected individuals that had an increase in CD4+CD69+ and CD8+CD38+ cells. Besides, individuals with IRIS presented higher increase in CD8+CD45RO+ cells than RR co-infected.
Conclusions: These results suggest that in spite of similarity in clinical profile and cellular pattern in skin lesions the cellular immune response is apparently systemic in patients with IRIS in contrast with RR. This is probably caused by rapidly reconstitution of immune system by HAART with an increase of memory T cells and should be considered in the treatment choice.
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