The role of ERBB2 gene polymorphisms in leprosy susceptibility

Mycobacterium leprae infects skin and peripheral nerves causing deformities and disability. The M. leprae bacterium binds to ErbB2 on the Schwann cell surface causing demyelination and favoring spread of the bacilli and causing nerve injury. Polymorphisms at the ERBB2 gene were previously investigated as genetic risk factors for leprosy in two Brazilian populations but with inconsistent results. Herein we extend the analysis of ERBB2 variants to a third geographically distinct population in Brazil. Our results show that there is no association between the genotyped SNPs and the disease (p > 0.05) in this population. A gene set or pathway analysis under the genomic region of ERBB2 will be necessary to clarify its regulation under M. leprae stimulus

Polymorphism in the interleukin-10 gene is associated with overactive bladder phenotype associated with HTLV-1 infection

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2019-09-25T17:50:36Z No. of bitstreams: 1 Braz M. Polymorphism.pdf: 1025178 bytes, checksum: 9cc4fd4830fb312c252fce453b637066 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-09-25T17:51:08Z (GMT) No. of bitstreams: 1 Braz M. Polymorphism.pdf: 1025178 bytes, checksum: 9cc4fd4830fb312c252fce453b637066 (MD5)Made available in DSpace on 2019-09-25T17:51:08Z (GMT). No. of bitstreams: 1 Braz M. Polymorphism.pdf: 1025178 bytes, checksum: 9cc4fd4830fb312c252fce453b637066 (MD5) Previous issue date: 2019-01-30Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT N˚ 573839/2008-5).Universidade Federal da Bahia. Pós-graduação em Ciências da Saúde. Salvador, BA, Brasil / Universidade Federal da Bahia. Serviço de Imunologia. Salvador, BA, Brasil.Universidade Federal da Bahia. Serviço de Imunologia. Salvador, BA, Brasil.Universidade Federal da Bahia. Pós-graduação em Ciências da Saúde. Salvador, BA, Brasil / Universidade Federal da Bahia. Serviço de Imunologia. Salvador, BA, Brasil.Universidade Federal da Bahia. Pós-graduação em Ciências da Saúde. Salvador, BA, Brasil / Universidade Federal da Bahia. Serviço de Imunologia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisas Clinicas. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Brasília, DF, Brasil.Universidade Federal da Bahia. Serviço de Imunologia. Salvador, BA, Brasil / Universidade Estadual de Feira de Santana. Departamento de Ciências Biológicas. Feira de Santana, BA, Brasil / Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Brasília, DF, Brasil.Universidade Federal da Bahia. Pós-graduação em Ciências da Saúde. Salvador, BA, Brasil / Universidade Federal da Bahia. Serviço de Imunologia. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Brasília, DF, Brasil.Universidade Federal da Bahia. Serviço de Imunologia. Salvador, BA, Brasil.Human T-cell lymphotropic virus type 1 (HTLV-1)-associated inflammatory diseases are not well understood; however, their clinical manifestations may be influenced by the host genetic background. Methods: We genotyped 298 individuals with HTLV-1 and 380 controls for interleukin-10 (IL10) gene variants—rs3024496, rs1800871, rs1800896—and used logistic regression analysis to determine their association with clinical phenotypes. Results: No association with HTLV-1 infection was observed. However, allele A of rs1800896 (1082bp upstream) was associated with protection against neurological impairment, specifically overactive bladder (OR=0.447, 95% CI 0.28–0.70, p=0.001). Conclusions: Our data suggests that IL10 regulation ameliorates neurological damage in HTLV-1 infections

Whole blood profiling of leprosy type 1(reversal) reactions highlights prominence of innate immune response genes

Abstract Background The major factors contributing for nerve damage and permanent disabilities in leprosy are type 1 or reversal reactions (RR) and type 2 or erythema nodosum leprosum (ENL). Gene profiling of leprosy reactions have shown that different pathways are activated during the course of reactions, which is consistent with the exacerbated immune response exhibited by these patients. Methods We used qPCR to screen a panel of 90 genes related to the immune response in leprosy in RNA-derived peripheral leukocytes of patients with (N = 94) and without leprosy reactions (N = 57) in order to define expression signatures correlated to RR or ENL. Results Our results show that there is a marked signature for RR in the blood, comprising genes mostly related to the innate immune responses, including type I IFN components, autophagy, parkins and Toll like receptors. On the other hand, only Parkin was differentially expressed in the ENL group. Conclusions The data put together corroborates previous work that brings evidence that an acute uncontrolled exacerbated immune response designed to contain the spread of M. leprae antigens might be cause of RR pathogenesis. Identifying a blood profile useful to predict leprosy reactions prior to its development might help to reduce the morbidity associated to this disabling disease

Polymorphisms in genes TLR1, 2 and 4 are associated with differential cytokine and chemokine serum production in patients with leprosy

BACKGROUND Leprosy or hansen’s disease is a spectral disease whose clinical forms mostly depends on host’s immune and genetic factors. Different Toll-like receptors (TLR) variants have been described associated with leprosy, but with some lack of replication across different populations. OBJECTIVES To evaluate the role of polymorphisms in genes TLR1, TLR2 and TLR4 and susceptibility to leprosy in a genetic case control study; to verify the association between genotypes of these markers and the immunological profile in the serum of patients with leprosy. METHODS Pre-designed TaqMan® assays were used to genotype markers at TLR1 (rs4833095, rs5743551), TLR2 (rs7656411, rs3804099) and TLR4 (rs1927914, rs1927911). A panel of cytokines and chemokines was accessed by enzime-linked immunosorbent assay (ELISA) test in the serum of a subgroup of patients with and without leprosy reactions. FINDINGS Our results show an association between the T allele of rs3804099 at the TLR2 gene and increased risk for leprosy per se [Odds ratio (OR) = 1.296, p = 0,022]. In addition, evaluating the association between different genotypes of the TLR1, 2 and 4 markers and cytokine/chemokine serological levels, IL-17 appears as an immunological marker regulated by the polymorphism of the three TLR genes evaluated, whereas different TLR1 genotypes were associated with differential production of IL-12p40 and MCP-1(CCL2). Furthermore, other relevant serum markers such as CXCL-10 and IL-6 seemed to be regulated by TLR2 variants and IL-1β was related to TLR4 genotypes. MAIN CONCLUSIONS All together our data points that the tested TLR markers may have a regulatory role in the immunity against Mycobacterium leprae, by driving the host’s production of key cytokines and chemokines involved in the pathogenesis of this disease