Chest
Volume 115, Issue 2, February 1999, Pages 428-433
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Clinical Investigations
EPIDEMIOLOGY AND DIAGNOSIS
Human Leukocyte Antigen-Associated Susceptibility to Pulmonary Tuberculosis: Molecular Analysis of Class II Alleles by DNA Amplification and Oligonucleotide Hybridization in Mexican Patients

https://doi.org/10.1378/chest.115.2.428Get rights and content

Background

Pulmonary tuberculosis (PTB) develops by a complex combination of environmental factors with genetic susceptibility. In this context, an association between human leukocyte antigens (HLAs) and tuberculosis has been 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 primer technique and PCR sequence-specific oligonucleotide hybridization in a Mexican population.

Setting

This study was conducted at the Clinical Service of Tuberculosis and the Department of Immunology, National Institute of Respiratory Diseases, México City, México.

Patients

Four groups were examined: 95 healthy subjects; 50 nonimmunosuppressed PTB patients; 15 HIV-infected patients (stage IVc in the Centers for Disease Control and Prevention [CDC] classification system for AIDS) with PTB; 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% confidence 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 significantly increased in nonimmunosuppressed patients with PTB when compared with healthy subjects. By contrast, frequencies of allele DQB1*0402 and antigens DR4 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 susceptibility may not be relevant in patients with severe immunodeficiency diseases such as AIDS.

Section snippets

Study Population

Fifty randomly selected nonimmunosuppressed patients with pulmonary TB (PTB) were included in this study. The study subjects were unrelated Mexican patients who were residents of Mexico City and were hospitalized at the National Institute of Respiratory Diseases at the time of the study. In all cases, the diagnosis of TB was confirmed by light microscopy, which revealed the presence of acid-fast bacilli in sputum, and by culture of the M tuberculosis.

The criteria for considering patients with

Results

The study included 50 nonimmunosupressed patients (with a mean[± SD] age of 39.1 ± 13.0 years). Evaluated as control subjects were 95 healthy individuals (35.4 ± 10.1 years of age), 37 HIV-infected patients without infectious or neoplastic disease (31 ± 8.9 years of age), 15 immunosuppressed (HIV-infected) patients with TB (31.1 ± 5.7 years of age), and 20 healthy non-HIV-infected homosexual subjects (26.3 ± 8.5 years of age). The latter control group displayed no significant differences in HLA

Discussion

Molecular typing has proven useful for clarifying the genetic susceptibility associated with the HLA system. Tissue or cell sampling may now be achieved by examining the cell nucleic acid rather than by using serologic methods, thus increasing the sensitivity of the sampling. In our study, PCR, in combination with the sequence-specific oligonucleotide probes, clearly showed an association between the frequencies of the DQA1*0101, DQB1*0501, and DRB1*1501 alleles and PTB. The aforementioned

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