Human leucocyte antigens and cytokine gene polymorphisms and tuberculosis.

Purpose: Several genes encoding different cytokines and human leucocyte antigens (HLA) may play crucial roles in host susceptibility to tuberculosis (TB). Our objective was to investigate whether these genes might be associated with protection from or susceptibility to TB. Materials and Methods: Genomic DNA from patients with TB (n = 30) and ethnically matched controls (n = 30) was genotyped by using sequence-specific primers-polymerase chain reaction and sequence-specific oligonucletid methods. Results: Our results demonstrated that HLA-Cw*01 [P = 0.05, odds ration (OR) (95% confidence interval) = 2.269 (1.702-3.027)] allele frequency was significantly more common in TB patients than in healthy controls, and HLA-Cw*01 may be associated with susceptibility to TB. Analysis of cytokine allele frequencies showed that interleukin (IL)-10, -819 C and -592 C alleles was significantly more common in TB patients than in controls (pc: 0.038 and 0.017, respectively). From the IL-10 cluster, a positive significant difference was found at positions -1082 and -592 C/C (pc: 0.027 and 0.054, respectively) genotypes. Although these differences could be explained by the highest frequency of C/C and G/G homozygous patients with TB, in contrast to the control group, statistically significant differences for the C/C genotype however were lost after Bonferroni correction of the P-values. Conclusion: Altogether, our results suggest that the polymorphisms in HLA (class I) and cytokine (IL-10) genes may affect the susceptibility to TB and increase the risk of developing the disease.

The effect of nitric oxide combined with fluoroquinolones against Salmonella enterica serovar Typhimurium in vitro

Two regulons, soxRS and marRAB, are associated with resistance to quinolones or multiple antibiotic in Salmonella enterica serovar Typhimurium. These regulons are activated by nitric oxide and redox-cycling drugs, such as paraquat and cause on activation of the acrAB-encoded efflux pump. In this study, we investigated the effect of nitric oxide (NO) alone and in combination with ofloxacin, ciprofloxacin, and pefloxacin against S. typhimurium clinical isolates and mutant strains in vitro. We did not observe synergistic effect against clinical isolates and SH5014 (parent strain of acr mutant), while we found synergistic effect against PP120 (soxRS mutant) and SH7616 (an acr mutant) S. typhimurium for all quinolones. Our results suggest that the efficiencies of some antibiotics, including ofloxacin, ciprofloxacin, and pefloxacin are decreased via activation of soxRS and marRAB regulons by NO in S. enterica serovar Typhimurium. Further studies are warranted to establish the interaction of NO with the genes of Salmonella and, with multiple antibiotic resistance

HLA tissue types in nonresponders to hepatitis B vaccine.

Genetic factors are implicated in the response of normal subjects to hepatitis B vaccine. In order to investigate the immunogenetic factors associated with nonresponsiveness to hepatitis B vaccine, 93 health care workers were vaccinated with hepatitis B vaccine. Initial nonresponders (antibody not detected or antibody detected but < 10 mlU/ml) were revaccinated. Only 12 (12.9%) of the 93 health care workers, who had anti-HBs levels of 10 mlU/ml or less after revaccination were defined as absolute nonresponders. HLA typing were performed in these 12 nonresponders, Anti-HBs levels were determined by ELISA method in mlU/ml units. HLA-A,B,C,DR, and DQ typing was performed using the microcytotoxicity test. The HLA-A10 (pc less than 0.01) and CW4 (pc less than 0.006) were decreased whereas DR7 (pc less than 0.09) was increased in nonresponders. Although our initial results suggest the importance of genetic modulation of responsiveness to hepatitis B vaccine, a formal demonstration of the mode of inheritance of unresponsiveness to hepatitis B vaccine and the explanation of the role of genes in this matter will require further studies of families.