Umeda Naoto, Matsumoto Isao, Kawaguchi Hoshimi, Kurashima Yuko, Kondo Yuya, Tsuboi Hiroto, Ogishima Hiroshi, Suzuki Takeshi, Kagami Yayoi, Sakyu Takuya, Ishigami Akihito, Maruyama Naoki, Sumida Takayuki
Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan.
Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
Clin Rheumatol. 2016 May;35(5):1181-8. doi: 10.1007/s10067-015-3082-z. Epub 2015 Sep 29.
The objectives of this study are to investigate the prevalence of PAD4 and anti-PAD4 antibodies (Abs) in autoimmune diseases and to clarify their association with anticitrullinated protein antibodies (ACPAs) and shared epitope (SE) in patients with rheumatoid arthritis (RA). Levels of human PAD4 and anti-PAD4 Abs in serum or plasma were measured using sandwich ELISA. Samples were obtained from patients with RA (n = 148), SLE (n = 36), or SS (n = 37) and from healthy controls (HCs; n = 40). Antibodies against cyclic citrullinated glucose-6-phosphate isomerase (GPI) (CCG)-2, CCG-7, anti-CEP-1, and anti-CCP Abs were also measured using ELISA. Patients with RA were genotyped for HLA-DRB1. The human PAD4 and anti-PAD4 Ab levels were compared with the ACPA and SE in patients with RA. The PAD4 levels were 111.9 U/ml in the RA, 30.4 U/ml in the SLE, 81.9 U/ml in the SS patients, and 46.6 U/ml in the HCs. The PAD4 levels were significantly higher in the RA than in the SLE patients or the HCs. Anti-PAD4 Abs were detected in 29.7 % of the patients with RA, but not in the patients with SLE or SS, nor in the HCs. In the RA patients, the PAD4 levels in the anti-PAD4 Ab-negative group were significantly higher than those in the anti-PAD4 Ab-positive group. Moreover, anti-CCG-2, CCG-7, CEP-1, and anti-CCP Ab levels were significantly higher in the anti-PAD4 Ab-positive group than in the anti-PAD4 Ab-negative group. In the RA patients, the PAD4 levels were not correlated with ACPAs. Neither PAD4 nor anti-PAD4 Abs were significantly correlated with the presence of SE alleles. The PAD4 levels were higher in RA than in SLE or HC. Anti-PAD4 Abs appeared specifically in patients with RA. Moreover, anti-PAD4 Abs were associated with ACPAs.
本研究的目的是调查自身免疫性疾病中肽瓜氨酸脱亚氨酶4（PAD4）和抗PAD4抗体（Abs）的患病率，并阐明它们与类风湿关节炎（RA）患者中抗瓜氨酸化蛋白抗体（ACPAs）和共享表位（SE）的关联。使用夹心酶联免疫吸附测定法（ELISA）检测血清或血浆中人类PAD4和抗PAD4 Abs的水平。样本取自RA患者（n = 148）、系统性红斑狼疮（SLE）患者（n = 36）或干燥综合征（SS）患者（n = 37）以及健康对照者（HCs；n = 40）。还使用ELISA检测了抗环瓜氨酸化葡萄糖-6-磷酸异构酶（GPI）（CCG）-2、CCG-7、抗环瓜氨酸化纤维蛋白原（CEP）-1和抗环瓜氨酸化肽（CCP）Abs。对RA患者进行了人类白细胞抗原-DRB1（HLA-DRB1）基因分型。将RA患者的人类PAD4和抗PAD4 Ab水平与ACPAs和SE进行比较。RA患者的PAD4水平为111.9 U/ml，SLE患者为30.4 U/ml，SS患者为81.9 U/ml，HCs为46.6 U/ml。RA患者的PAD4水平显著高于SLE患者或HCs。在29.7%的RA患者中检测到抗PAD4 Abs，但在SLE或SS患者以及HCs中未检测到。在RA患者中，抗PAD4 Ab阴性组的PAD4水平显著高于抗PAD4 Ab阳性组。此外，抗PAD4 Ab阳性组的抗CCG-2、CCG-7、CEP-1和抗CCP Ab水平显著高于抗PAD4 Ab阴性组。在RA患者中，PAD4水平与ACPAs无相关性。PAD4和抗PAD4 Abs均与SE等位基因的存在无显著相关性。RA患者的PAD4水平高于SLE或HC。抗PAD4 Abs仅在RA患者中出现。此外，抗PAD4 Abs与ACPAs相关。
