HLA-A, -B, -DRB1, -DQA1, and -DQB1 profile in a population from southern Brazil.

The aim of this study was to determine the allele and haplotype frequencies of HLA-A, -B, -DRB1, and -DQB1 in a self-declared White population from the north and northwestern state of Paraná, southern Brazil, and compare the data with populations worldwide. The genotyping was performed with a group of 641 individuals, based on PCR-SSO and -SSP methods, and allele and haplotype frequencies were estimated. Comparisons with European, African, Asian, and Amerindian populations were performed. The most frequent allelic groups, alleles and haplotypes were: HLA-A*02, HLA-B*35, HLA-DRB1*07:01, HLA-DQB1*03:01, and HLA-A*01/B*08/DRB1*03:01. The results reinforced a predominance of a European composition in the self-declared White population from the north and northwestern Paraná.

T-cell autoreactivity to Hsp in human transplantation may involve both proinflammatory and regulatory functions.

Heat shock proteins (Hsp) are moving from the category of basically intracellular chaperone molecules to important proteins in both innate and acquired immune responses, with great potential for clinical application as immunomodulators. Both proinflammatory and regulatory Hsp-reactive T cells have been described in animal models of autoimmune diseases. To investigate the role of autoreactivity to Hsp60 and Hsp70 in human transplantation, we analyzed, sequentially, peripheral blood mononuclear cell proliferation and cytokine production before and at different time points after renal transplantation, as well as the modulation of proliferation to Hsp in the presence of exogenous cytokines. Proliferation to Hsp60 and Hsp70 in the pretransplantation (pre-Tx) period was significantly associated with rejection episodes in the first months post-Tx. In contrast, IL-4 production was significantly associated with absence of rejection. Addition of exogenous IL-4 distinctly modulated the proliferative response to Hsp60; inhibiting proliferation in 83% of patients in the early post-Tx period (0-6 months), in which rejection episodes occurred, and inducing proliferation in 62.5% of patients in the later period (>12-24 months), when no rejection was observed. Characterization of autoreactive anti-Hsp60 regulatory T cells may permit new approaches to control the proinflammatory response to the graft, as well as aggressive autoimmunity.

HLA typing in Brazilian boys with aromatic antiepileptic drug-induced DRESS.

CASES DESCRIPTION: We report two cases of drug rash with eosinophilia and systemic symptoms (DRESS) associated with the use of carbamazepine and phenytoin in Brazilian boys tested for human leukocyte antigen (HLA) class I and II alleles. The clinical manifestations were similar: a maculopapular eruption progressing to exfoliative erythroderma, fever, and lymphadenopathy. Leukocytosis, atypical lymphocytes, and liver injury were also observed. Assessment of causality using the Naranjo algorithm established a "probable" relationship (score 6) in both cases. Case 1 patient presented the following results of HLA typing: HLA-A*02,29 B*44,50 C*06,16 DRB1*01,07 DQA1*01,02. Case 2 patient presented the following results of HLA typing: HLAA*23,24 B*39,53 C*04,07 DRB1*04,08 DQA1*03,05 DQB1*03,03. CONCLUSION: Neither of the cases reported here presented HLA typing similar to that strongly associated with the occurrence of DRESS in Asian or European patients.

Genetic diversity of HCV in Brazil.

BACKGROUND: Many studies have documented the molecular epidemiological scenario of HCV within individual Brazilian states, but we still have an incomplete understanding of the dispersion dynamics of the virus in different regions throughout the country. METHODS: A total of 676 HCV NS5B gene sequences of subtypes 1a (n=321), 1b (n=170) and 3a (n=185), isolated from seven different Brazilian states covering four out of five regions were analysed in the present study. We also analysed 22 HCV NS5B gene sequences of minor genetic variants including genotype 2 (n=13), genotype 4 (n=6) and subtype 5a (n=3). Brazilian HCV sequences were aligned with sequences of non-Brazilian origin and subjected to maximum likelihood phylogenetic analyses. RESULTS: These analyses revealed that the Brazilian HCV epidemic resulted from multiple introductions and autochthonous transmission of subtypes 1a, 1b, 3a and genotypes 2, 4 and 5. Brazilian HCV subtype 1a epidemic is dominated by the dissemination of one major clade; while Brazilian HCV subtypes 1b and 3a epidemics are characterized by concurrent dissemination of several independent HCV lineages. Some HCV Brazilian lineages of subtypes 1a, 1b, 2b and 3a were successful in becoming established and disseminated through several regions in the country. Despite significant phylogenetic intermixing of Brazilian sequences, the distribution of HCV strains from different states across lineages was not completely homogeneous. CONCLUSIONS: These results demonstrate the existence of multiple introductions and local propagation of both prevalent and uncommon HCV genetic variants in Brazil and identify some major Brazilian HCV clades with nationwide dissemination. This study also suggests that the observed HCV diversity in Brazil has been shaped by both frequent viral migration among regions and in situ viral dissemination.