Association of Human Leukocyte Antigens Class I and II Variants with Susceptibility to Pulmonary Tuberculosis in a Caucasian Population from Northern Spain

Abstract

Background: Susceptibility to TB seems to be multifactorial, and the development of active disease is probably the result of complex interactions between the host and pathogen, influenced by environmental and genetic factors. The Human Leukocyte Antigen system or HLA seems to be one of these factors. Differences in the distribution of HLA alleles and haplotypes have been found worldwide with conflicting results among different populations and few data concerning Caucasian populations have been reported. Methods: Distribution of HLA class I and class II alleles was evaluated in 160 Spanish patients with pulmonary tuberculosis, all of them HIV negative, 109 latently infected individuals, and in 262 healthy individuals. All the subjects included in the study belonged to the same geographical area (Cantabria, northern Spain). Results: HLA-A*02 was found to be significantly more frequent in the latently infected group compared with the control group (34.86% versus 25.19%, p=0.009, OR 0.63 IC95% 0.45-0.89) and with patients with pulmonary tuberculosis (34.86% versus 25.79%, p=0.03, OR 0.65 IC95% 0.45-0.94). HLA-C*08 was found to be significantly more frequent in pulmonary tuberculosis patients compared with the control group (9.69% versus 5.34%, p=0.02, OR 1.91 IC95% 1.12-3.25). HLA-DRB1*04 was found to be significantly more frequent in pulmonary tuberculosis patients compared with the control group (17.19% versus 11.83%, p=0.037, OR 1.55 IC95% 1.04-2.29). Finally, HLA-DRB1*07 was found to be significantly more frequent in healthy and latently infected individuals compared with patients with pulmonary tuberculosis (19.66% & 21.10% versus 13.75%, p=0.036 & 0.034, OR 0.65 & 0.60 IC95% 0.44-0.96 & 0.38-0.94 respectively). The only haplotype which was significantly more frequent in pulmonary tuberculosis patients versus healthy individuals was the DRB1*04-DQA1*03-DQB1*03 extended three locus haplotype (p=0.04, OR 1.53 IC95% 1.03-2.72). All these differences disappeared after statistical correction for multiple comparisons. Conclusion: Although there were no significant differences in HLA alleles distribution among the three groups after statistical correction, there seems to be a slight trend of certain alleles in conferring protection against or susceptibility to pulmonary tuberculosis, at least in our population.