Heavy Chain Constant Region Usage in Antibodies to Peptidylarginine Deiminase 4 as a Marker of Disease Subsets in Rheumatoid Arthritis.
Heavy Chain Constant Region Usage in Antibodies to Peptidylarginine Deiminase 4 as a Marker of Disease Subsets in Rheumatoid Arthritis.
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DOI：
10.1002/art.42262
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发表时间：
2022-11
影响因子：
13.3
通讯作者：
Darrah, E.
中科院分区：
文献类型：
--
作者：
Gomez-Banuelos, E.;Shi, J.;Wang, H.;Danila, M., I;Bridges, S. L.;Giles, J. T.;Sims, G. P.;Andrade, F.;Darrah, E.
自身免疫性疾病中自身抗体同种型的研究对于鉴定临床相关的内型是有用的。在这里，我们研究了不同的同种型和IgG亚类的抗肽基精氨酸脱亚胺酶4（PAD 4）自身抗体的患病率和临床意义的个人与类风湿关节炎（RA）。采用ELISA法检测196例RA患者和64例健康对照者的抗PAD 4抗体类型。我们研究了抗PAD 4抗体与临床结果的关系。使用独立的RA队列确认相关特征。RA患者的抗PAD 4抗体IgG 1、IgG 2、IgG 3、IgG 4、伊加和IgE水平高于健康对照组（P均<0.001）。抗PAD 4 IgG 1、IgG 3和IgE与不同的特征相关。抗PAD 4 IgG 1可预测进行性放射学关节损伤（OR 4.88，P=0.005），尤其是在无基线关节损伤的RA患者（40% vs. 0%，P=0.003）或抗CCP和/或类风湿因子阴性的患者（OR 32，P=0.009）中。IgG 1也与较高水平的C-反应蛋白（P=0.006）和IL-6（P=0.021）相关。具有抗PAD 4 IgG 3的RA患者具有更高的基线关节损伤（平均SHS 13 vs. 7，P=0.046），而具有抗PAD 4 IgE的患者具有更高的DAS 28评分（平均4.0 vs. 3.5，P=0.025），类风湿结节更常见（31% vs. 16%，P=0.025）和间质性肺疾病（玻璃磨影）（24% vs. 9%，P=0.014）。在一个独立的RA队列中证实了抗PAD 4 IgG 1抗体与关节损伤的相关性。抗PAD 4 IgG 1、IgG 3和IgE抗体可识别RA中的离散疾病亚群，表明RA中重链使用驱动抗PAD 4抗体的不同效应机制。
The study of autoantibody isotypes in autoimmune diseases has been useful for identifying clinically relevant endotypes. Here, we studied the prevalence and clinical significance of different isotypes and IgG subclasses of anti-peptidylarginine deiminase 4 (PAD4) autoantibodies in individuals with rheumatoid arthritis (RA). Anti-PAD4 antibody types were determined by ELISA in 196 RA subjects and 64 healthy controls. We investigated associations of anti-PAD4 antibodies and clinical outcomes. Relevant features were confirmed using an independent RA cohort. Anti-PAD4 IgG1, IgG2, IgG3, IgG4, IgA, and IgE antibodies were more frequent in patients with RA than healthy controls (P<0.001 for all). Anti-PAD4 IgG1, IgG3 and IgE were associated with distinct features. Anti-PAD4 IgG1 was predictive of progressive radiographic joint damage (OR 4.88, P=0.005), especially in RA patients without baseline joint damage (40% vs. 0%, P=0.003) or in those negative for anti-CCP and/or rheumatoid factor (OR 32, P=0.009). IgG1 was also associated with higher levels of C-reactive protein (P=0.006) and IL-6 (P=0.021). RA patients with anti-PAD4 IgG3 had higher baseline joint damage (mean SHS 13 vs. 7, P=0.046), while those with anti-PAD4 IgE had higher DAS28 scores (mean 4.0 vs. 3.5, P=0.025), more frequent rheumatoid nodules (31% vs. 16%, P=0.025) and interstitial lung disease (glass ground opacification) (24% vs. 9%, P=0.014). Joint damage associations of anti-PAD4 IgG1 antibodies were corroborated in an independent RA cohort. Anti-PAD4 IgG1, IgG3 and IgE antibodies identify discrete disease subsets in RA, suggesting that heavy chain usage drives distinct effector mechanisms of anti-PAD4 antibodies in RA.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
DOI：
10.1002/art.23719
发表时间：
2008-06-15
期刊：
ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH
影响因子：
--
作者：
Giles, Jon T.;Ling, Shari M.;Bathon, Joan M.
通讯作者：
Bathon, Joan M.
影响因子：
3
作者：
Chung, Neo Christopher;Miasojedow, Blazej;Gambin, Anna
通讯作者：
Gambin, Anna
影响因子：
14.2
作者：
Schroeder, Harry W., Jr.;Cavacini, Lisa
通讯作者：
Cavacini, Lisa
类风湿性关节炎间质性肺疾病的发病率和死亡率：一项基于人群的研究。
影响因子：
--
作者：
Bongartz, Tim;Nannini, Carlotta;Medina-Velasquez, Yimy F.;Achenbach, Sara J.;Crowson, Cynthia S.;Ryu, Jay H.;Vassallo, Robert;Gabriel, Sherine E.;Matteson, Eric L.
通讯作者：
Matteson, Eric L.