目的:旨在探討牙齦卟啉單胞菌與類風濕關節炎(RA)高風險人群出現自身抗體之間的關係。
方法:研究對象包括:1)攜帶HLA-DR4的人群和2)一級親屬為RA患者的RA高風險人群。所有這些研究對象均不符合1987年ACR的RA分類標準。需檢測的自身抗體包括抗瓜氨酸化蛋白抗體(ACPA;ELISA法)和類風濕因子(RF;濁度測定法或ELISA法檢測IgA,IgM或IgG亞型抗體)。檢測到>1個RA相關自身抗體的個體被認為是自身抗體陽性個體(n=113);如ACPA或>2實驗檢測的RF陽性個體可被進一步分類為RA的高危人群(n=38)。自身抗體陰性的個體作為對照組(n=171)。檢測抗牙齦卟啉單胞菌、中間普雷沃菌、具核梭杆菌抗體。應用邏輯回歸的方式評估細菌抗體與不同分組之間的相關性。
結果:自身抗體陽性組和RA高風險組中抗牙齦卟啉單胞菌抗體的濃度高於自身抗體陰性組。抗中間普雷沃菌抗體或抗具核梭杆菌抗體濃度在各組間均沒有差異。經多變量調整後抗牙齦卟啉單胞菌抗體的濃度(而不是抗中間普雷沃菌抗體或抗具核梭杆菌抗體)與自身抗體陽性和RA高風險狀態顯著相關。
結論:牙齦卟啉單胞菌的免疫原性與RA高風險人群中RA相關性自身抗體的出現顯著相關。這些結果支持了這一假說:牙齦卟啉單胞菌的感染在RA發病早期的自身抗原免疫失耐受過程中發揮了重要作用。
附原文:
Objective.To examine the relationship of Porphyromonas gingivalis to the presence of autoantibodies in individuals at risk of rheumatoid arthritis (RA).
Methods.Study participants included the following:1) a cohort enriched in subjects with HLA–DR4 and 2) subjects at risk of RA by virtue of having a first-degree relative with RA. None of the study subjects satisfied the American College of Rheumatology 1987 classification criteria for RA. Autoantibodies measured included anti–citrullinated protein antibody (ACPA; by second-generation anti–cyclic citrullinated peptide antibody enzyme-linked immunosorbent assay[ELISA]) and rheumatoid factor (RF; by nephelometry or ELISA for IgA, IgM, or IgG isotype). Individuals were considered autoantibody positive (n=113) if they had >1 RA-related autoantibody; individuals were further categorized as high risk (n=38) if they had ACPA or positive findings >2 assays for RF. Autoantibody negative individuals (n=171) served as a comparator group. Antibody to P gingivalis, P intermedia, and F nucleatum were measured. Associations of bacterial antibodies with group status were examined using logistic regression.
Results.Anti–P gingivalis concentrations were higher in high-risk (P= 0.011) and autoantibody positive group (P=0.010) than in the autoantibody negative group. There were no group differences in anti–P intermedia or anti–F nucleatum concentrations. After multivariable adjustment, anti–P gingivalis concentrations (but not anti–P intermedia or anti–F nucleatum) were significantly associated with autoantibody-positive and high-risk status (P < 0.05).
Conclusion.Immunity to P gingivalis, but not P intermedia or F nucleatum, is significantly associated with the presence of RA-related autoantibodies in individuals at risk of RA. These results support the hypothesis that infection with P gingivalis may play a central role in the early loss of tolerance to self antigens that occurs in the pathogenesis of RA.
引自:Ted R, Mikuls, Geoffrey M, Thiele, et al. Porphyromonas gingivalis and Disease-Related Autoantibodies in Individuals at Increased Risk of Rheumatoid Arthritis.ARTHRITIS & RHEUMATISM, Vol. 64, No. 11, November 2012, pp 3522–3530.