TGF-ß1 polymorphism in American tegumentary leishmaniasis in a Southern Brazilian population.

INTRODUCTION: Genetic polymorphisms define the cytokine production leading to susceptibility or resistance to diseases. We studied the cytokine polymorphism in the development of tegumentary leishmaniasis (TL). METHODS: Genotyping of TNF-α, TGF-ß1, IFN-γ, IL-6, and IL-10 were performed by polymerase chain reaction assay. RESULTS: G and C alleles of TGF- ß1 (codon 25) were the most common in controls and patients, respectively. G/G was the most frequent genotype in controls, and G/C and C/C in patients. CONCLUSIONS: G/G genotype of codon 25 in TGF-ß1 appeared to confer resistance, and G/C and C/C genotypes, susceptibility to TL in this population.

TGF-ß1 polymorphism in American tegumentary leishmaniasis in a Southern Brazilian population

Abstract INTRODUCTION: Genetic polymorphisms define the cytokine production leading to susceptibility or resistance to diseases. We studied the cytokine polymorphism in the development of tegumentary leishmaniasis (TL). METHODS: Genotyping of TNF-α, TGF-β1, IFN-γ, IL-6, and IL-10 were performed by polymerase chain reaction assay. RESULTS: G and C alleles of TGF- β1 (codon 25) were the most common in controls and patients, respectively. G/G was the most frequent genotype in controls, and G/C and C/C in patients. CONCLUSIONS: G/G genotype of codon 25 in TGF-β1 appeared to confer resistance, and G/C and C/C genotypes, susceptibility to TL in this population.

Discrepancies in HLA typing: use of different methods to confirm doubtful or inconclusive results / Discrepâncias na tipagem HLA: diferentes métodos para confirmar resultados duvidosos ou inconclusivos

The major histocompatibility complex (MHC) is a set of genes found on the short arm of chromosome 6. MHC molecules in human beings are known as human leukocyte antigens (HLA). HLA polymorphism can be determined by serological and molecular typing methods, which may yield discordant results. The present analysis performed HLA typing of samples with discordant results by PCR-SSP and PCR-SSO, so that typing discrepancies could be clarified. The cross-sectional study analyzed 33 samples from individuals included in an HLA-disease association study. Discrepant alleles were observed in 6 of 33 samples. Discordant samples were retyped using One Lambda Micro SSP™, Dynal RELI™ SSO and Luminex™ SSO assays for HLA class I (HLA-A, HLA-B) and class II (HLA-DRB1) molecules. The three methods produced concordant results after HLA retyping. Human error occurred in interpreting the initial results, which led to discrepancies in the results obtained. The participation of experienced professionals and the availability of at least two different methods to confirm doubtful or inconclusive results are mandatory for effective HLA typing.

O complexo principal de histocompatibilidade (MHC) é um conjunto de genes encontrados no braço curto do cromossomo 6. Em humanos, as moléculas de MHC são conhecidas como antígenos leucocitários humanos (HLA). Polimorfismo HLA pode ser determinado por métodos de tipagem sorológica e molecular que são susceptíveis de produzir resultados discordantes. Este estudo teve como objetivo realizar a tipagem HLA de amostras com resultados discordantes por PCR-SSP e-SSO e para esclarecer discrepâncias de digitação. Este estudo transversal analisou 33 amostras de indivíduos incluídos em um estudo de associação HLA-doença. Alelos discrepantes foram observados em seis das 33 amostras. Amostras discordantes foram retyped usando One Lambda Micro SSP™, Dynal RELI™ SSO Luminex e ensaios ™ SSO para HLA de classe I (HLA-A, HLA-B) e classe II (HLA-DRB1) moléculas. Todos os três métodos apresentaram resultados concordantes após HLA redigitação. Houve erro humano na interpretação dos resultados iniciais o que levou a uma discrepância entre os resultados obtidos. Concluiu-se que a participação de profissionais experientes e com a disponibilidade de pelo menos dois métodos diferentes para confirmar os resultados duvidosos ou inconclusivos são essenciais para a tipagem de HLA eficaz.

Effect of the chemokine receptor CCR5 in the development of American cutaneous leishmaniasis in a Southern Brazilian population.

American cutaneous leishmaniasis (ACL) shows a wide spectrum of clinical and immunopathological manifestations. The CCR5 chemokine receptor directs the immune response to a Th1 pattern and the mutant allele of this genotype (Δ32/Δ32) results in a less effective response, thus leading to a milder inflammation. The objective of the present study was to investigate the effect of the CCR5 chemokine receptor in the pathogenesis of ACL in a population of Southern Brazil. The frequency of the genotypes and their association with ACL were studied in 111 patients and compared with 218 control subjects. Genotyping was performed using samples amplified by polymerase chain reaction with sequence specific primers (PCR­SSP). The groups varied in chronological age (P<0.00001), but showed no differences in gender (P=0.0696) or ethnicity (P=0.2944). The frequency of the CCR5/Δ32 genotype did not differ between the patient and control groups (P=0.3009). The Δ32/Δ32 deletion was not observed in any individual involved in the study. The analysis of the genotypes observed no significant difference in the frequency of the CCR5/Δ32 genotype between the ACL and control groups, however the subgroup of patients with a recurrence of the lesion showed a higher frequency of the CCR5/Δ32 mutation (P=0.020), indicating a possible effect of this allele in the pathogenesis of ACL. Nevertheless, more studies are required to elucidate the role of CCR5 in the pathogenesis of ACL.