Abstract
AIM—To determine the presence of HLA antigens in people with blinding trachoma. METHODS—Fifty Omanis with blinding trachoma were serologically typed for HLA A, B, C, DR, and DQ antigens and DNA typed for class II DRβ and DQβ alleles and compared with a population of 100 healthy controls. RESULTS—χ2 analysis of serological reactions did not reveal any significant differences in HLA antigen frequencies after correction of probability, although DR4, DR7, and DR53 were completely absent in the patients and all of the patients were HLA DQ1 positive. In the case of DQ1 the relative risk was 22.6 (95% confidence interval of 20.7-24.7). Class II DNA low resolution DRβ typing showed a significant increase in HLA DR16 (pc = 0.036, relative risk = 3.8) and a significant decrease in HLA DR53 (pc = 0.018, relative risk = 0.05 ). CONCLUSION—The finding that HLA DR16 (a DR2 subtype) is associated with susceptibility to blinding trachoma, a disease that is caused by an intracellular micro-organism, is consistent with reports of an HLA DR2 association with leprosy and tuberculosis, diseases also caused by an intracellular micro-organism. Similarly, resistance to leprosy is associated with HLA DR53 as is the case with blinding trachoma described here. It is postulated that HLA DR2 or subtypes in association with HLA DQ 1 may enable an intracellular micro-organism to enter the cell or are involved in presentation of peptides derived from intracellular micro-organisms to T lymphocytes initiating a delayed hypersensitivity or autoimmune reaction. These findings are the first report that genetic factors are of major importance in the development and protection against blinding trachoma.
Full Text
The Full Text of this article is available as a PDF (104.5 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bobo L., Munoz B., Viscidi R., Quinn T., Mkocha H., West S. Diagnosis of Chlamydia trachomatis eye infection in Tanzania by polymerase chain reaction/enzyme immunoassay. Lancet. 1991 Oct 5;338(8771):847–850. doi: 10.1016/0140-6736(91)91502-l. [DOI] [PubMed] [Google Scholar]
- Brahmajothi V., Pitchappan R. M., Kakkanaiah V. N., Sashidhar M., Rajaram K., Ramu S., Palanimurugan K., Paramasivan C. N., Prabhakar R. Association of pulmonary tuberculosis and HLA in south India. Tubercle. 1991 Jun;72(2):123–132. doi: 10.1016/0041-3879(91)90039-u. [DOI] [PubMed] [Google Scholar]
- Conway D. J., Holland M. J., Campbell A. E., Bailey R. L., Krausa P., Peeling R. W., Whittle H. C., Mabey D. C. HLA class I and II polymorphisms and trachomatous scarring in a Chlamydia trachomatis-endemic population. J Infect Dis. 1996 Sep;174(3):643–646. doi: 10.1093/infdis/174.3.643. [DOI] [PubMed] [Google Scholar]
- Courtright P., Lewallen S., Howe R. Cell-mediated immunity in trachomatous scarring. Evidence from a leprosy population. Ophthalmology. 1993 Jan;100(1):98–104. doi: 10.1016/s0161-6420(93)31686-6. [DOI] [PubMed] [Google Scholar]
- HALDANE J. B. The estimation and significance of the logarithm of a ratio of frequencies. Ann Hum Genet. 1956 May;20(4):309–311. doi: 10.1111/j.1469-1809.1955.tb01285.x. [DOI] [PubMed] [Google Scholar]
- Hill A. V., Allsopp C. E., Kwiatkowski D., Anstey N. M., Twumasi P., Rowe P. A., Bennett S., Brewster D., McMichael A. J., Greenwood B. M. Common west African HLA antigens are associated with protection from severe malaria. Nature. 1991 Aug 15;352(6336):595–600. doi: 10.1038/352595a0. [DOI] [PubMed] [Google Scholar]
- Joko S., Numaga J., Fujino Y., Masuda K., Hirata R., Maeda H. [HLA and uveitis in leprosy]. Nippon Ganka Gakkai Zasshi. 1995 Oct;99(10):1181–1185. [PubMed] [Google Scholar]
- Mabey D. C., Bailey R. L., Dunn D., Jones D., Williams J. H., Whittle H. C., Ward M. E. Expression of MHC class II antigens by conjunctival epithelial cells in trachoma: implications concerning the pathogenesis of blinding disease. J Clin Pathol. 1991 Apr;44(4):285–289. doi: 10.1136/jcp.44.4.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mehra N. K., Rajalingam R., Mitra D. K., Taneja V., Giphart M. J. Variants of HLA-DR2/DR51 group haplotypes and susceptibility to tuberculoid leprosy and pulmonary tuberculosis in Asian Indians. Int J Lepr Other Mycobact Dis. 1995 Jun;63(2):241–248. [PubMed] [Google Scholar]
- Miller S. A., Dykes D. D., Polesky H. F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215–1215. doi: 10.1093/nar/16.3.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Svejgaard A., Ryder L. P. HLA and disease associations: detecting the strongest association. Tissue Antigens. 1994 Jan;43(1):18–27. doi: 10.1111/j.1399-0039.1994.tb02291.x. [DOI] [PubMed] [Google Scholar]
- Taylor H. R., Rapoza P. A., West S., Johnson S., Munoz B., Katala S., Mmbaga B. B. The epidemiology of infection in trachoma. Invest Ophthalmol Vis Sci. 1989 Aug;30(8):1823–1833. [PubMed] [Google Scholar]
- Thylefors B., Dawson C. R., Jones B. R., West S. K., Taylor H. R. A simple system for the assessment of trachoma and its complications. Bull World Health Organ. 1987;65(4):477–483. [PMC free article] [PubMed] [Google Scholar]
- Todd J. R., West B. C., McDonald J. C. Human leukocyte antigen and leprosy: study in northern Louisiana and review. Rev Infect Dis. 1990 Jan-Feb;12(1):63–74. doi: 10.1093/clinids/12.1.63. [DOI] [PubMed] [Google Scholar]
- Venkataram M. N., White A. G., Leeny W. A., al Suwaid A. R., Daar A. S. HLA antigens in Omani patients with vitiligo. Clin Exp Dermatol. 1995 Jan;20(1):35–37. doi: 10.1111/j.1365-2230.1995.tb01279.x. [DOI] [PubMed] [Google Scholar]
- el-Asrar A. M., Van den Oord J. J., Geboes K., Missotten L., Emarah M. H., Desmet V. Immunopathology of trachomatous conjunctivitis. Br J Ophthalmol. 1989 Apr;73(4):276–282. doi: 10.1136/bjo.73.4.276. [DOI] [PMC free article] [PubMed] [Google Scholar]