HLA-DQB1 and -DPB1 allele profile in HIV infected patients with and without pulmonary tuberculosis of south India .

Selvaraj, P.; Raghavan, S.; Swaminathan, S.; Alagarasu, K.; Narendran, G.; Narayanan, P.R.

Infection, Genetics and Evolution; 2008; 8; 664–671.

Abstract: We made an attempt to find out whether Human Leucocyte Antigen (HLA)-DQB1 and -DPB1 alleles are associated with susceptibility or resistance to Human Immunodeficiency Virus (HIV) infection and development of pulmonary tuberculosis (PTB) in HIV infected patients. The allelic profile of HLA-DQB1 and -DPB1 was studied among HIV patients without pulmonary tuberculosis (HIV+PTB-) (n = 115), HIV patients with pulmonary TB (HIV+PTB+) (n = 59), HIV negative PTB patients (HIV-PTB+) (n = 110) and healthy controls (n = 112) by polymerase chain reaction and sequence specific oligonucleotide probe method. Increased frequency of HLA-DQB1*050301 was observed in HIV+PTB- [p = 0.024, Odds Ratio (OR) 2.30, 95% Confidence Interval (CI) 1.11–4.90] and HIV+PTB+ patients (p = 0.044, OR 2.41, 95% CI 1.01–5.73) compared to healthy controls, suggesting that DQB1*050301 may be associated with susceptibility to HIV infection as well as development of PTB in HIV patients. Underrepresentation of HLA-DPB1*1501 was observed in HIV-PTB+ ( p = 0.002, Pc = 0.034) and HIV+PTB+ ( p = 0.036) patients compared to healthy controls, suggesting that DPB1*1501 may be associated with protection against PTB development both in HIV positive and negative subjects. Analysis on the amino acid variation in the peptide binding pocket at b 69 position of HLA-DPB1 molecules revealed that the b 69 arginine containing HLA-DPB1 alleles and the genotype lysine/arginine were underrepresented in HIV-PTB+ (allele: p = 0.003, Pc = 0.009; genotype: p = 0.0002, Pc = 0.001) and HIV+PTB+ (allele: p = 0.016, Pc = 0.048; genotype: p = 0.026). This suggests that HLA-DPB1 alleles with arginine may be associated with protection against development of PTB in both HIV infected as well as uninfected individuals. Further, the haplotypes HLA-DRB1*1502-DPB1*0201 and HLA-DQB1*0601-DPB1*0201 ( Pc < 0.001) and HLADRB1* 1502-DQB1*0601-DPB1*0201 ( p = 0.006, OR 5.09, 95% CI 1.42–22.66) were significantly overrepresented in HIV+PTB+ patients compared to healthy controls suggesting that genetic susceptibility to PTB development in HIV patients may be modulated by interplay between HLA class II alleles, besides HLA class I alleles.

Keywords: HLA-DQB1; -DPB1; HIV; HIV-PTB

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