Higher Treg FoxP3 and TGF-β mRNA Expression in Type 2 Reaction ENL (Erythema Nodosum Leprosum) Patients in Mycobacterium leprae Infection

Abstract

Background and Aim: The pathology of leprosy is determined by the host immune response to Mycobacterium leprae. Almost 40% of patients with leprosy undergo immune-mediated inflammatory episodes such as type 1 reactions and Erythema Nodosum Leprosum (ENL or type 2 reactions). Regulatory T (Treg) is a subset of T cells that are involved in the immune response. Treg cells express Forkhead Box P3 (FoxP3), which plays a role in suppressing the immune response. FoxP3 may work alongside Transforming Growth Factor Beta (TGF-β) to down-regulate T cells responses, leading to the antigen-specific anergy associated with leprosy, whereas ENL occurrs mostly in multibacillary leprosy patients. Based on that, the aim of our study was to analyze Treg FoxP3 and TGF-β mRNA expression in type 2 reactions ENL with Mycobacterium leprae infection. Methods: Forty-nine newly diagnosed multibacillary (MB) leprosy patients attending the Dermatovenereology Clinic of Leprosy Subdivision, Sanglah General Hospital, Denpasar, Indonesia, were included in the study. The study group consists of 25 leprosy patients with ENL and 24 non-ENL leprosy patients. Twenty-five patients were included in the study as healthy controls. In this study, Treg FoxP3 and TGF-β mRNA expressions were identified with the Real-time PCR method. Analysis of Variant (ANOVA), Chi-square test and odds ratio (OR) calculation were used; p<0.05 was considered statistically significant. Results: The result of this study showed that the mean of Treg FoxP3 mRNA expression was 13.3 ± 2.9 on ENL leprosy patients, 11.6 ± 4.1 on non-ENL, and 9.3 ± 1.2 on healthy controls. The mean of TGF-β mRNA expression was 11.7 ± 2.7 on ENL leprosy patients, 9.5 ± 3.6 on non-ENL, and 9.3 ± 1.2 in healthy patients. Statistical analysis for Treg FoxP3 and TGF-β mRNA level between ENL, non-ENL patients and healthy control group showed significance at p<0.05. Conclusion: From this study, it was concluded that higher Treg FoxP3 and TGF-β mRNA expressions were found in type 2 reaction ENL patients with Mycobacterium leprae infection. The role played by Treg FoxP3 and TGF-β in type 2 reaction episodes can possibly provide a new target for the treatment of this still-challenging complication of leprosy. Further studies are required to determine the involvement of other cytokines in type 2 reaction ENL patients.