#48-OR
ASPARTIC ACID HOMOZYGOSITY AT CODON 57 OF HLA-DQ BETA IMPAIRS THE HOST IMMUNE RESPONSE TO TUBERCULOSIS.
Julio C. Delgado MD 1, Andres Baena 1, Sok Thim 2 and Anne Goldfeld MD 1. 1 Infectious Diseases, CBR Institute for Biomedical Research, Boston, MA, USA and 2 Cambodian Health Committee, Phnom Pehn, Cambodia .
A functional link between HLA polymorphisms and breakdown of tuberculosis infection latency has not been established. Here we show a significant association between homozygosity for HLA alleles encoding an aspartic acid at codon 57 of the HLA-DQ beta chain (HLA-DQ 
57-Asp) and breakthrough of TB latency in a cohort of 436 patients and 107 controls from Cambodia (P = 0.001; OR = 3.05; 95% CI, 1.53-6.07). HLA-class II null cells transduced with HLA-DQ 57-Asp had a significantly reduced ability to bind a peptide from the central region of the M. tuberculosis-derived ESAT-6 protein and stimulate interferon-gamma production from CD4+ T cells compared to HLA-DQ 57- alanine (Ala) transduced cells (Figures 1 and 2). These data demonstrate the the first correlation between TB disease, HLA associations and impaired peptide binding and T cell activation. Since alanine at this same codon predisposes humans and mice to autoimmune diabetes, these data also support the hypothesis that susceptibility to autoimmune diabetes is a consequence of natural selection for enhance TB resistance.
