Bright R, Proudman S M, Rosenstein E D, Bartold P M
Department of Dentistry, Colgate Australian Clinical Dental Research Centre, University of Adelaide, SA 5005, Australia.
Rheumatology Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia; Discipline of Medicine, University of Adelaide, Australia.
Med Hypotheses. 2015 Jun;84(6):570-6. doi: 10.1016/j.mehy.2015.03.006. Epub 2015 Mar 6.
The remarkable similarity in inflammatory response and pathology of periodontal disease and rheumatoid arthritis has been recognized for several decades. However, how these two disease may be interrelated has been less clear. During the pathogenesis of rheumatoid arthritis there is a preclinical immunological phase which precedes the clinical manifestation of rheumatoid arthritis. During this phase serum autoantibodies appear many years before the clinical signs and symptoms of rheumatoid arthritis become apparent. To date, the two best studied autoantibodies have been rheumatoid factor and anti-citrullinated protein antibodies (ACPA). Of these the production of ACPA has been considered very important due to their high predictive value in future manifestation of rheumatoid arthritis. Citrullination is a common post-translational modification of proteins based on the enzymatic conversion of arginine into citrulline. Extra-articular citrullination and production of ACPA, as a priming immunological experience, is well documented in many tissues including the inflamed gingival tissues associated with periodontal disease. More recently, carbamylation of proteins has also been implicated in the pathogenesis of rheumatoid arthritis in a manner similar to citrullination. Carbamylation is a post translational modification of proteins by an enzyme-independent modification of lysine residues against which autoantibodies are subsequently induced. In this article we hypothesise that, like citrullination, carbamylation of proteins and associated antibody production during the gingival inflammation associated with gingivitis and periodontitis may play a role in the pathogenesis of rheumatoid arthritis.
几十年来，人们已经认识到牙周病和类风湿性关节炎在炎症反应和病理学方面存在显著相似性。然而，这两种疾病之间的相互关系尚不太明确。在类风湿性关节炎的发病过程中，有一个临床前免疫阶段，先于类风湿性关节炎的临床表现出现。在这个阶段，血清自身抗体在类风湿性关节炎的临床体征和症状出现之前许多年就已出现。迄今为止，研究得最多的两种自身抗体是类风湿因子和抗瓜氨酸化蛋白抗体（ACPA）。其中，ACPA的产生被认为非常重要，因为它们对类风湿性关节炎的未来表现具有很高的预测价值。瓜氨酸化是一种基于精氨酸酶促转化为瓜氨酸的常见蛋白质翻译后修饰。关节外瓜氨酸化和ACPA的产生，作为一种引发免疫的经历，在许多组织中都有充分记录，包括与牙周病相关的发炎牙龈组织。最近，蛋白质的氨甲酰化也以类似于瓜氨酸化的方式被认为与类风湿性关节炎的发病机制有关。氨甲酰化是一种蛋白质的翻译后修饰，通过赖氨酸残基的非酶促修饰进行，随后会诱导产生针对该修饰的自身抗体。在本文中，我们假设，与瓜氨酸化一样，在与牙龈炎和牙周炎相关的牙龈炎症过程中，蛋白质的氨甲酰化及相关抗体产生可能在类风湿性关节炎的发病机制中起作用。
