A “case control” study on the rôle of HLA DR4 in severe periodontitis and rapidly progressive periodontitis

Abstract

HLA DR4 antigens have been considered as a risk factor in periodontal disease. The aim of this "case control" study was to verify and to provide fuller clarification of such data. "Cases" or patients had to be aged between 20 and 48 years. They presented at least 5 sites spread over several teeth with an attachment loss equal or greater than 6 mm, and 10 sites spread over several teeth with periodontal pockets equal to or greater than 5 mm. Verification with a WHO probe showed an individual CPITN score of 4. Moreover, subjects whose average CPITN score for the 6 sextants was less than 3 were excluded from the study. Among these "severe periodontitis" patients, a subgroup was distinguished composed of subjects aged 20-35 years who presented, in accordance with the cases by Katz and co-workers, 5 or more teeth showing pocket depths of 6 mm or more. The dental chartings of these subjects showed an attachment loss of more than 3 mm on certain teeth over an inter-exam period of 1-3 years. They all displayed obvious loss of bony support in the affected sites. This constituted the "rapidly progressive periodontitis" subgroup. The "controls" were all over 20 years of age, and it was clinically verified that they were free of periodontal disease. There were 48 "cases" and 55 "controls". HLA typing of patients and controls was performed using "sequence oligoprobe hybridization after polymerase chain reaction" in accordance with the 11th International Workshop. This method allowed the detection of DR4 alleles as well as DR4 subtypes. The ethno-geographic origin of the subjects, considered as a confounding variable, was neutralized by stratified analysis. Subtypes 0401, 0404, 0405 and 0408 tended to be more frequent (p=0.08) in the cases (Severe Periodontitis). Focusing on analysis of "rapidly progressive periodontitis" in subjects aged 20-35 years, a very significant Mantel-Haenszel chi2 was obtained (p=0.0058) which led to a Mantel-Haenszel standardized odds ratio (OR) equal to 17. The 95% confidence interval was 1.03<0.R.<180.10. In conclusion, this supports previous reports and gives further clarification: in particular subtypes 0401, 0404, 0405 and 0408 can be considered as a risk factor for "rapidly progressive periodontitis". It should be noted that these determinants have been implicated in rheumatoid arthritis.

A spectrum of susceptibility to rheumatoid arthritis within HLA-DRB1: stratification by autoantibody status in a large UK population

“…[39][40][41] This is of interest in light of suggestions that *04-SE alleles are associated with rapidly progressive periodontal disease. 42 Our finding that HLA-DRB1*0401 is more strongly associated with ACPA-positive RA than HLADRB1*0404 is consistent with most previous reports, 10,[43][44][45] although not all. 46 Subtle differences with other reports of a hierarchy of risk (*044*104*01) 47 may be attributed to differences in the genetic or environmental background, and/or to differences in statistical methods.…”

Rheumatoid arthritis is linked to oral bacteria: etiological association

“…HLA-DR4 tissue antigens are found at high frequencies both in patients with periodontitis and in those with RA [30][31][32].…”

Anti‐Tumor Necrosis Factor‐Alpha Therapy and Periodontal Parameters in Patients With Rheumatoid Arthritis

“…Так, установлена ассоциация ПД с HLA-DR4, присутству-ющим у 50% больных РА и встречающимся лишь у 14% здоровых лиц [49,50]. Тяжелое течение РА определяет на-личие HLA-DRB1, с которым также ассоциируется ПД [7,[51][52][53].…”