Periodontal attachment loss in HIV-infected patients is associated with the major histocompatibility complex 8.1 haplotype (HLA-A1,B8,DR3)

Periodontal attachment loss is mediated by overproduction of tumour necrosi s factor (TNF) and interleukin (IL)-1, and appears to have a genetic compon ent. The 8.1 major histocompatibility complex (MHC) ancestral haplotype (HL A-A1,B8,TNFA-308(2),DR3) is associated with elevated TNF production and pre disposes carriers to several autoimmune/immuno-pathological disorders, incl uding rapid progression of HIV disease, but not early onset periodontal dis ease in healthy individuals. Rather a high proportion of subjects with seve re periodontal disease carry allele 2 at IL-1A-889 and IL-1B+3953. We predi cted that genetic associations may be different or clearer in HIV patients, as they often show elevated production of TNF and IL-1 and periodontal att achment loss. Hence periodontal parameters and IL-1 polymorphisms were asse ssed in HIV-positive subjects expressing HLA-B8 with or without other marke rs of the 8.1 haplotype. Of 16 HLA-B8 subjects, 13 demonstrated elevated pr obing pocket depth and clinical attachment loss. The difference was statist ically significant and did not correlate with smoking, age, CD4 T-cell coun ts, HN viral load or levels of dental plaque. As TNFA-308 (allele 2) was pr esent in four non-B8 subjects who had minimal attachment loss, it may not m ediate the effect of the 8.1 haplotype. Moreover, polymorphisms at IL-1A-88 9 and IL-1B+3953 did not significantly affect periodontal parameters. Thus a central MHC gene characteristic of the 8.1 haplotype was the dearest dete rminant of periodontal attachment loss in HIV-infected individuals.xm.