Human leukocyte antigen-associated susceptibility to pulmonary tuberculosis - Molecular analysis of class II alleles by DNA amplification and oligonucleotide hybridization in Mexican patients

Background: Pulmonary tuberculosis (PTB) develops by a complex combination of environmental factors with genetic susceptibility. In this context, an a ssociation between human leukocyte antigens (HLAs) and tuberculosis has bee n examined in several populations, but results have been controversial. Design and Measurements: A prospective evaluation of class II HLA genotypes was completed by the polymerase chain reaction (PCR) sequence-specific pri mer technique and PCR sequence-specific oligonucleotide hybridization in a Mexican population. Setting: This study was conducted at the Clinical Service of Tuberculosis a nd the Department of Immunology, National Institute of Respiratory Diseases , Mexico City, Mexico. Patients: Four groups were examined: 95 healthy subjects; 50 nonimmunosuppr essed PTB patients; 15 HIV-infected patients (stage IVc in the Centers for Disease Control and Prevention [CDC] classification system for AIDS) with P TB; and 37 HIV-infected patients in the asymptomatic stage (CDC stage II). Results: The frequencies of alleles DQA1*0101 (odds ratio [OR], 6.18; 95% c onfidence interval [CI], 2.38 to 16.08), DQB1*0501 (OR, 6.16; 95% CI, 2.44 to 17.71), and DRB1*1501 (OR, 7.92; 95% CI, 2.71 to 23.14) were significant ly increased in nonimmunosuppressed patients with PTB when compared with he althy subjects. By contrast, frequencies of allele DQB1*0402 and antigens D R4 and DR8 were significantly decreased in patients with PTB, Additionally, a significantly higher frequency of the DRB1*1101 allele was found in HIV- positive subjects (OR, 6.67; 95% CI, 2.13 to 20.83). Conclusion: The genetic influence associated with the HLA system appears to have an important role in the development of PTB, although this susceptibi lity may not be relevant in patients with severe immunodeficiency diseases such as AIDS.