Association between human leukocyte antigen class II (HLA-DRB and -DQB) alleles and outcome of exposure to : a cross-sectional study in Nairobi, Kenya.

INTRODUCTION

human leukocyte antigen (HLA) class II alleles play an important role in the early immune response to tuberculosis (TB) by presenting antigenic peptides to CD4+ T cells, hence polymorphisms in those genes can influence the efficiency of the immune response to infection and progression to active disease.

METHODS

an analytical cross-sectional study of adult pulmonary tuberculosis (PTB) patients at Mbagathi County Hospital, Nairobi and their HHCs. Sociodemographic data were captured on questionnaires and clinical data extracted from patient files. Intravenous blood samples were drawn for interferon-gamma release assay (IGRA) to determine latent tuberculosis infection (LTBI) among HHCs, and for extraction of DNA used in typing of HLA-DQB1 and HLA-DRB1 alleles by PCR sequence specific primer amplification. Chi-square and Fisher's exact test were used to compare the HLA type II allele frequencies of LTBI negative HHCs, LTBI positive HHCs and active TB patients. Logistic regression was used to adjust for HIV status.

RESULTS

the HLA-DQB1 and HLA-DRB1 alleles were analyzed in 17 PTB and 37 HHCs. Nineteen (19) HHCs were LTBI positive, while 18 were LTBI negative. The frequency of DRB31 was 0.17-fold lower [95% CI=0.03-0.83] among PTB patients compared to HHCs before adjustment for HIV status (p=0.048). The frequency of the DRB52 allele was significantly higher (p=0.013) among PTB patients (23.5%) compared to HHCS (0.00%). After adjusting for HIV status, the frequency of DRB1*14 was 12-fold higher [95% CI=1.11-138.2] among PTB patients compared to HHCs (p=0.040).

CONCLUSION

the higher frequencies of HLA-DRB52 and HLA-DRB114 alleles in PTB patients suggest a likely association with progression to active PTB. The higher frequency of HLA-DRB3*1 allele among LTBI negative HHCs shows its likely protective role against M. tuberculosis infection in this population.