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Human Leukocyte Antigen (HLA)-B, DRB1, and DQB1 Allotypes Associated with Disease and Protection of Trachoma Endemic Villagers

¹From the National Human Genome Center, Howard University, Washington, DC; ²Department of Internal Medicine, Baystate Medical Center-Tufts University School of Medicine, Springfield, Massachusetts; ³Emergency Medicine, Johns Hopkins University, Baltimore, Maryland; ⁴Calgary Laboratory Services, Tissue Typing Laboratory, Calgary AB, Canada; ⁵Department of Community and Family Health, Howard University College of Medicine, Baltimore, Maryland; ⁶Adult Infectious Diseases, Johns Hopkins University, Baltimore, Maryland; ⁷National Institutes of Health, National Institute of Allergy and Infectious Diseases, Laboratory of Immunoregulation, Bethesda, Maryland; and the ⁸Dana Center for Investigative Ophthalmology, Johns Hopkins University, Baltimore, Maryland.

PURPOSE. Trachoma remains the leading preventable infectious cause of blindness in developing countries. Human leukocyte antigen (HLA) associations with ocular disease severity and persistent Chlamydia trachomatis infection of Tanzanians living in trachoma-endemic villages were examined to determine possible protective candidate allotypes for vaccine development.

METHODS. Buccal swab scrapes were taken from subjects in the Trichiasis Study Group (TSG), which studied females only, and the Family Trachoma Study (FTS), which compared persistently infected probands who had severe disease with disease-free siblings and parents. DNA was purified for polymerase chain reaction sequence-specific oligonucleotide identification of HLA-DRB1, DQB1, and B allotypes. Infection was detected from conjunctival scrapes using a C. trachomatis-specific PCR-enzyme immunoassay for the MOMP-1 gene.

RESULTS. In the TSG, DR*B11 (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26–0.90; P = 0.02) was significantly associated with lack of trichiasis, whereas HLA-B*07 (OR, 3.26; 95% CI, 1.42–7.49; P = 0.004) and HLA-B*08 (OR, 5.12; 95% CI, 1.74–15.05; P = 0.001) were associated with trichiasis. In addition, HLA-B*14 was significantly associated with inflammatory trachoma + follicular trachoma (OR, 3.76; 95% CI, 1.70–8.33; P = 0.04). There were no significant allele frequencies for the FTS.

CONCLUSIONS. The data suggest that HLA-DRB*11 may offer protection from trichiasis in trachoma hyperendemic villages. Complete allotype identification and designation of its respective protective CD4⁺ T-cell antigens could provide a testable candidate vaccine for blindness prevention. Additionally, buccal swab DNA was sufficiently stable when acquired under harsh field conditions and stored long term in the freezer for low-resolution HLA typing.