骨关节炎中翻译后修饰蛋白的自身抗体。

Auto-antibodies to post-translationally modified proteins in osteoarthritis.

机构信息

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and the NIHR Leeds Biomedical Research Centre, Leeds, UK.

Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands.

出版信息

Osteoarthritis Cartilage. 2021 Jun;29(6):924-933. doi: 10.1016/j.joca.2021.03.008. Epub 2021 Mar 20.

DOI:10.1016/j.joca.2021.03.008

PMID:33757859

Abstract

OBJECTIVE

Autoantibodies (AutoAbs) have been observed in osteoarthritis (OA) with broad antigenicity, although their prevalence and role remain unclear. Post-translational modification (PTMs) of proteins (oxidation, carbamylation, citrullination) is associated with synovitis and can lead to AutoAb development. Given the prevalence of synovitis, we explored whether AutoAbs to PTM-antigens are common in OA compared with rheumatoid arthritis (RA).

METHODS

Serum (n = 895) was obtained from healthy controls, OA and RA patients; and arthritic synovial fluid (SF, n = 290). ELISAs were used to quantify anti-citrullinated peptide (ACPA), anti-carbamylated protein (anti-CarP), anti-oxidized collagen (anti-ROS-CI/CII) antibodies.

RESULTS

In sera, positivity for PTM-antigens AutoAbs was observed at a lower frequency in OA with 64.1% (95%CI: 57.2-70.1%) more ACPA+ and 29.8% (21.0-37.3%) more anti-CarP + patients in RA (both P < 0.0001). Levels of ACPA, anti-CarP were also lower in OA (P < 0.0001). Anti-ROS-CII positivity was lower in OA compared to RA (16.6%, 4.8-28.6%) less frequent, P = 0.033) but not anti-native-CII. There was no impact of age/gender on AutoAbs associations with diseases either looking at positivity or levels. In SF, OA patients were often ACPA+ (45.9%) although less frequently than in RA (P = 0.004). Anti-CarP were rarely observed (<5% all samples). All collagen AutoAbs were more frequent in RA compared to OA (all P < 0.010) but only levels of anti-CII and anti-ROS-CII were significantly higher in they RA (P < 0.050).

CONCLUSION

Although the frequency of AutoAbs for PTM proteins were lower in OA sera compared to RA, a higher proportion of OA SF were positive. The relative retention of AutoAbs in the OA joint requires further investigation.

摘要

目的

尽管自身抗体（AutoAbs）在骨关节炎（OA）中具有广泛的抗原性，但它们的流行程度和作用仍不清楚。蛋白质的翻译后修饰（PTMs）（氧化、氨甲酰化、瓜氨酸化）与滑膜炎有关，并可导致自身抗体的产生。鉴于滑膜炎的普遍性，我们探讨了与类风湿关节炎（RA）相比，OA 患者中是否常见针对 PTM 抗原的自身抗体。

方法

从健康对照者、OA 和 RA 患者中获得血清（n=895）；并从关节炎性滑膜液（SF，n=290）中获得。使用 ELISA 定量测定抗瓜氨酸化肽（ACPA）、抗氨甲酰化蛋白（anti-CarP）、抗氧化胶原（anti-ROS-CI/CII）抗体。

结果

在血清中，OA 患者中 PTM 自身抗体的阳性率较低，RA 患者中 ACPA+的患者比例为 64.1%（95%CI：57.2-70.1%），anti-CarP+的患者比例为 29.8%（21.0-37.3%）（均 P<0.0001）。OA 患者的 ACPA 和 anti-CarP 水平也较低（P<0.0001）。与 RA 相比，OA 患者的 anti-ROS-CII 阳性率较低（少 16.6%，4.8-28.6%），P=0.033），但 anti-native-CII 则不然。无论是从阳性率还是从水平来看，年龄/性别对自身抗体与疾病之间的关联均无影响。在 SF 中，OA 患者通常为 ACPA+（45.9%），但低于 RA（P=0.004）。anti-CarP 很少见（<5%的所有样本）。与 OA 相比，所有胶原自身抗体在 RA 中更为常见（均 P<0.010），但仅在 RA 中，anti-CII 和 anti-ROS-CII 的水平显著更高（均 P<0.050）。