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Severe type 1 upgrading leprosy reaction in a renal transplant recipient: a paradoxical manifestation associated with deficiency of antigen-specific regulatory T-cells?

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Vieira, Ana Paula ; Bianconcini Trindade, Maria Angela ; de Paula, Flavio Jota ; Sakai-Valente, Neusa Yurico ; da Silva Duarte, Alberto Jose ; Carvalhinho Lemos, Francine Brambate ; Benard, Gil
Número total de Autores: 7
Tipo de documento: Artigo Científico
Fonte: BMC INFECTIOUS DISEASES; v. 17, APR 24 2017.
Citações Web of Science: 2

Background: Due to its chronic subclinical course and large spectrum of manifestations, leprosy often represents a diagnostic challenge. Even with proper anti-mycobacteria treatment, leprosy follow up remains challenging: almost half of leprosy patients may develop reaction episodes. Leprosy is an infrequent complication of solid organ transplant recipients. This case report illustrates the challenges in diagnosing and managing leprosy and its reactional states in a transplant recipient. Case presentation: A 53-year-old man presented 34 months after a successful renal transplantation a borderline-tuberculoid leprosy with signs of mild type 1 upgrading reaction (T1R). Cutaneous manifestations were atypical, and diagnosis was only made when granulomatous neuritis was found in a cutaneous biopsy. He was successfully treated with the WHO recommended multidrug therapy (MDT: rifampicin, dapsone and clofazimine). However he developed a severe T1R immediately after completion of the MDT but no signs of allograft rejection. T1R results from flare-ups of the host T-helper-1 cell-mediated immune response against Mycobacterium leprae antigens in patients with immunologically unstable, borderline forms of leprosy and has been considered an inflammatory syndrome in many aspects similar to the immune reconstitution inflammatory syndromes (IRS). The T1R was successfully treated by increasing the prednisone dose without modifying the other immunosuppressive drugs used for preventing allograft rejection. Immunological study revealed that the patient had a profound depletion of both in situ and circulating regulatory T-cells and lack of expansion of the Tregs upon M. leprae stimulation compared to T1R leprosy patients without iatrogenic immunosuppression. Conclusions: Our case report highlights that leprosy, especially in the transplant setting, requires a high degree of clinical suspicion and the contribution of histopathology. It also suggests that the development of upgrading inflammatory syndromes such as T1R can occur despite the sustained immunosuppressors regimen for preventing graft rejection. Our hypothesis is that the well-known deleterious effects of these immunosuppressors on pathogen-induced regulatory T-cells contributed to the immunedysregulation and development T1R. (AU)

Processo FAPESP: 16/08730-6 - Patogenicidade fúngica: efeito do tabagismo, resposta imune e a modulação vacinal na paracoccidioidomicose e na histoplasmose
Beneficiário:Carlos Pelleschi Taborda
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 14/15286-0 - Atuação de células T reguladoras em episódios reacionais na hanseníase
Beneficiário:Gil Benard
Linha de fomento: Auxílio à Pesquisa - Regular