HLA-A and HLA-DRB1 amino acid polymorphisms are associated with susceptibility and protection to pulmonary tuberculosis in a Greek population

BackgroundPulmonary tuberculosis remains the single deadliest infectious disease causing high mortality in humans leading to 1.4 million deaths annually. Inherited genetic factors may explain why some people resist infection more successfully than others.MethodsThe polymorphisms of HLA-class I (-A, -B) and class II (-DRB1, -DQB1) genes have been evaluated using DNA-based typing in a population of 86 non-immunosuppressed, unrelated Greek patients with PTb and 46 healthy unrelated people without a history of PTb, who were all tested purified protein derivative positive (>14 mm).ResultsThe HLA-A R114 and HLA-DRβN37 residues are associated with susceptibility. They operate independently from each other and their effect is detected when the population is evaluated for their concurrent presence (A R114 positive or DRβN37 positive or A R114 and DRβN37 positive). Furthermore the HLA-A S77 appears to have a protective role, however in the presence of the DRβN37, the A-S77 does not exert its protective effect.ConclusionThe HLA residues A-S77, A-R114 and DRβN37 in combination with PTb antigenic elements possibly modulate T-cell responses against MTb that lead to either protection or susceptibility. The HLA-A and -DRB1-dependent T-cell networks may interact among themselves and influence each other resulting in different PTb phenotypes.