Human Leukocyte Antigen (HLA)-B, DRB1, and DQB1 Allotypes Associated with Disease and Protection of Trachoma Endemic Villagers
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Authors: Abbas, Muneer; Bobo, Linda D.; Hsieh, Yu-Hsiang; Berka, Noureddine; Dunston, Georgia; Bonney, George E.; Apprey, Victor; Quinn, Thomas C.; West, Sheila K.
Abstract
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. (Invest Ophthalmol Vis Sci. 2009; 50: 1734-1738) DOI:10.1167/iovs.08-2053
REMARKABLE SEQUENCE RELATEDNESS IN THE DNA ENCODING THE MAJOR OUTER-MEMBRANE PROTEIN OF CHLAMYDIA-PSITTACI (KOALA TYPE-I) AND CHLAMYDIA-PNEUMONIA
GENE
Authors: GIRJES, AA; CARRICK, FN; LAVIN, MF
Abstract
DNA encoding the major outer membrane protein (MOMP) of the koala type-I strain of Chlamydia psittaci (pathogen responsible for blindness and infertility in koalas) was cloned and sequenced. Comparison with momp gene sequences from other chlamydial species revealed a remarkable degree of homology (> 97%) with that of the human pathogen, Chlamydia pneumoniae. In comparison, the sequence only shared 75% DNA sequence homology with other C. psittaci members and 69% homology with C. trachomatis. The open reading frame consisted of 1167 bp encoding a 389-amino acid (aa) pre-MOMP including a leader sequence of 23 aa, similar to the C. pneumoniae gene. These genes were closely related even within the four variable domains (86-100% homology). Specific antibodies were capable of distinguishing between koala type I and C. pneumoniae. This very high degree of relatedness between C. pneumoniae, a human pathogen, and an individual strain of C. psittaci in the momp gene raises further questions on the host specificity, classification and evolutionary relationships of the different chlamydial species.