Interferon-gamma Low producer genotype +874 overrepresented in Bacillus Calmette-Guerin nonresponding children.

BACKGROUND: There are limited reports on the influence of the immune regulatory genotypes on the efficacy of Bacillus Calmette-Guerin (BCG) in man. This study was designed to evaluate the influence of the cytokine genotype interferon (IFN)-gamma +874T/A on T cell in vitro assays in BCG nonresponders (negative to either in vivo or in vitro test with purified protein derivative or both). METHODS: Ninety healthy children who were without any clinical evidence of the disease, 45 with a BCG-scar and the remaining 45 without scar were assessed for in vitro T cell responses. CD4+ and CD8+ cell counts were measured by flow cytometry. r32kDaBCG (Ag85A-BCG) protein was used to stimulate T cells and IFN-gamma cytokine concentration in the cultures were measured by enzyme-linked immunosorbent assay. Polymorphism in IFN-gamma (+874T/A) region was detected by amplification refractory mutation system-polymerase chain reaction. RESULTS: T cell subsets were within the normal range in all subjects. Children with TT genotype showed significantly higher antigen-induced IFN-gamma (P < 0.001) as compared with those with AT/AA genotype. The highest values were observed in children with TT genotype combined with positive antigen-specific peripheral blood mononuclear cells proliferation. Seventy-five percent of the vaccinated children with TT genotype showed high amounts of stimulated IFN-gamma compared with 66% of scar negative and 16% of scar positive but with AA genotype. CONCLUSIONS: IFN-gamma (+874T/A) polymorphism seemed to be a strong and independent predictor for clinical outcome of both scar-positive and scar-negative children. These results may help in planning future vaccination strategies. The ability to mount in vitro lymphoproliferation did not distinguish the success or failure of BCG vaccination nor predict susceptibility to the disease.

Role of HLA-B51 and HLA-B52 in susceptibility to pulmonary tuberculosis.

MHC class I-restricted CD8+ T cells are important for the generation of protective immune responses in MTB infection. CD8+ CTL (cytotoxic T-lymphocyte)-derived IFN-g may be especially important both for cells lacking MHC class II molecules, e.g. in the lung and for macrophages where mycobacteria can evade recognition during chronic infection by sequestering their antigens away from sensitized CD4+ T cells. This study was designed to detect any association of MHC class I (HLA-B) molecules with pulmonary tuberculosis. A total of 75 individuals, comprising of 33 patients with pulmonary tuberculosis; 12 HIV patients who developed tuberculosis and 30 healthy controls, were included in the study. They were typed for HLA-B by the PCR-SSP method. The results of only HLA-B alleles, which are highly significant, are presented here. The number of healthy individuals with HLA-B52 was significantly high when compared to the patient groups (healthy versus TB: 21.2% versus 0.0%, OR=0.0, P<0.0001, P(c)=0.003; healthy versus HIV-TB: 21.2% versus 16.7%; OR=0.74; P<0.001; P(c)=0.003). In contrast, the number of patients, both TB- and HIV-TB-positive, with HLA-B51 was significantly high when compared to the healthy group of individuals (TB versus healthy: 36.7% versus 3%; OR=18.53; P<0.0001; P(c)=0.001; HIV-TB versus healthy: 41.7% versus 3%; OR=22.86; P<0.0001; P(c)=0.001). Only one healthy control was positive to HLA-B51; however this individual also had HLA-B52. The results of this study suggest that HLA-B52(5) has a negative, i.e. a protective association and HLA-B51(5) has a positive (susceptible) association, for pulmonary tuberculosis. Studies on HLA-B51 and HLA-B52 in a larger population to assess their role in tuberculosis may be useful for TB-vaccination strategies, since HLA profiles are likely to be related to vaccine efficacy.

Association of HLA DQ B1* and HLA DR B1* alleles with goitrous juvenile autoimmune hypothyroidism--a case control study.

The present study was designed to analyze the distribution of HLA DQ B1* and DR B1* in patients with goitrous juvenile autoimmune hypothyroidism from Hyderabad, India. Analysis indicated an increase in the frequencies of HLA DQ B1* 03 allele (P < 0.000) and HLA DR B1* 04 (P < 0.05) alleles in this group of patients when compared to the controls, whereas the frequency of DQB1* 05 was found to be decreased in patients' group compared to the controls (p < 0.01). To conclude, we report a positive correlation between DQ B1* 03 and DR B1* 04 and goitrous juvenile autoimmune hypothyroidism, whereas DQB1* 05 is observed to be negatively correlated with this thyroid dysfunction. Since the disease-susceptible HLA class II alleles appear to differ in various ethnic groups for some autoimmune diseases, the observed association from Indian series of patients holds significance.