The role of ERBB2 gene polymorphisms in leprosy susceptibility

Rêgo, Jamile Leão; Oliveira, Joyce Moura; Santana, Nadja de Lima; Machado, Paulo Roberto Lima; Castellucci, Léa

doi:10.1016/j.bjid.2014.12.008

Cited by 5 publications

(2 citation statements)

References 15 publications

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“…All controls were inquired about personal or family history of leprosy prior sample collection. The characteristics of the patients cohort are described elsewhere (Rego et al 2015). A subset of 52 leprosy subjects was used for the enzime-linked immunosorbent assay (ELISA) tests, providing a sample of 17 without reaction (10 PB; 7 MB) and 35 with reactions (22 with type I reaction/RR; 13 with type II reaction/ENL).…”

Section: Methodsmentioning

confidence: 99%

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

Santana

Rêgo

Oliveira

et al. 2017

Mem. Inst. Oswaldo Cruz

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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.

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Section: Methodsmentioning

confidence: 99%

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

Santana

Rêgo

Oliveira

et al. 2017

Mem. Inst. Oswaldo Cruz

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“…Leprosy presents a wide variety of clinical presentations, including the indeterminate (I), tuberculoid (TT), borderline (BT, BB, BL) and lepromatous (LL) forms. In addition, about 20–50% of leprosy patients, depending on the population studied, can be affected by acute inflammatory episodes known as leprosy reactions, as so called type 1 (Reversal Reaction) or type 2 (Erythema Nodosum Leprosum- ENL) [ 4 , 5 ]. Either RR or ENL are observed in all borderline forms prior, during or after completion of multidrug therapy.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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BackgroundThe 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.MethodsWe 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.ResultsOur 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.ConclusionsThe 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.

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Molecular Pathogenesis of Leprosy

Bokhary

Phung

2016

Curr Trop Med Rep

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The role of ERBB2 gene polymorphisms in leprosy susceptibility

Cited by 5 publications

References 15 publications

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

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

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

Molecular Pathogenesis of Leprosy

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