Department of Dentistry, University of Adelaide, Adelaide, SA, Australia.
Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA.
J Periodontal Res. 2018 Feb;53(1):139-143. doi: 10.1111/jre.12486. Epub 2017 Oct 17.
Postranslational modification of proteins can lead to the production of autoantibodies and loss of immune tolerance. This process has been hypothesised to be a critical factor in the pathogenesis of rheumatoid arthritis. The objective of this study was to demonstrate that inflamed human gingival tissue provides an extrasynovial source of malondialdehyde-acetaldehyde adducts, citrullinated and carbamylated proteins all of which are considered to be linked to the development of rheumatoid arthritis. Identification of such modified proteins in inflamed gingiva may explain, in part, how inflammation of the periodontal tissues may influence the development of rheumatoid arthritis.
Gingival biopsies of healthy, mild and moderate periodontitis were triple stained with antibodies against malondialdehyde-acetaldehyde adducts, citrullinated and carbamylated proteins.
Assessment of healthy gingival tissue revealed negligible staining for carbamylated, malondialdehyde-acetaldehyde (MAA), or citrullinated proteins. Mild periodontitis was positive for all three modifications. Furthermore, there was an increase in staining intensity for carbamylated, citrullinated and MAA-modified proteins in moderate periodontitis. Negative staining results were observed for the isotype controls.
This study provides evidence for the presence of citrullinated, carbamylated and MAA adduct modified proteins in inflamed periodontal tissues. The potential for these proteins to play a role in autoimmunity in a multi-system inflammatory syndromic disease model now needs to be determined.
蛋白质的翻译后修饰可导致自身抗体的产生和免疫耐受的丧失。该过程被假设是类风湿关节炎发病机制中的一个关键因素。本研究的目的是证明发炎的人牙龈组织提供了丙二醛-乙醛加合物、瓜氨酸化和氨甲酰化蛋白的 extrasynovial 来源,所有这些都被认为与类风湿关节炎的发展有关。在发炎的牙龈中鉴定出这些修饰蛋白可以部分解释牙周组织的炎症如何影响类风湿关节炎的发展。
使用针对丙二醛-乙醛加合物、瓜氨酸化和氨甲酰化蛋白的抗体对健康、轻度和中度牙周炎的牙龈活检进行三重染色。
对健康牙龈组织的评估显示,氨甲酰化、丙二醛-乙醛(MAA)或瓜氨酸化蛋白的染色可忽略不计。轻度牙周炎对所有三种修饰均呈阳性。此外,中度牙周炎中氨甲酰化、瓜氨酸化和 MAA 修饰蛋白的染色强度增加。同种型对照观察到阴性染色结果。
本研究为炎症性牙周组织中存在瓜氨酸化、氨甲酰化和 MAA 加合物修饰蛋白提供了证据。这些蛋白在多系统炎症综合征疾病模型中是否具有自身免疫作用的潜力尚需确定。