PAD4在抗中性粒细胞胞浆抗体相关性小血管炎中的作用及意义

摘要/Abstract

摘要： 目的：探讨肽酰基精氨酸脱亚胺酶4（peptidylarginine deiminase type 4，PAD4）在抗中性粒细胞胞浆抗体（antineutrophil cytoplasmic antibody, ANCA）相关性小血管炎（ANCA-associated vasculitis, AAV）的发病机制及疾病活动中的临床意义，并对慢性支气管炎与AAV的发病关系做初步探讨。方法：收集13例AAV患者、13例慢性支气管炎和支气管扩张（chronic bronchitis and bronchiectasis, CB）患者、11例类风湿性关节炎（rheumatoid arthritis, RA）患者的发作期与缓解期血清，11例原发性慢性肾病（chronic kidney disease, CKD）患者的血清，以及12例健康对照的血清。用ELISA法检测血清PAD4的水平，分别比较不同组别血清PAD4的表达差异，并进一步研究AAV患者中PAD4与伯明翰血管炎活动性评分（Birmingham Vasculitis Activity Score, BVAS）的相关性。结果：（1）在发作期与缓解期的AAV组、RA组以及发作期的CB组，PAD4水平明显高于正常对照组(P<0.001，α′=0.007)，而在CB组患者缓解期以及CKD组患者中，PAD4水平与正常对照相比差异无统计学意义（分别为P=0.02，P=0.085，α′=0.007）。（2）在单纯AAV组、AAV伴CB组及单纯CB组患者的发作期中，PAD4水平差异无统计学意义，但在缓解期时，单纯CB患者的PAD4水平最低。（3）部分CB组患者的PAD4在缓解期时仍维持较高水平。（4）AAV肾损害组患者发作期的PAD4水平与BVAS评分呈正相关(r=0.71, P=0.02)。结论：PAD4参与了AAV的发生、发展，部分慢性支气管炎患者与AAV的发病有一定相关性。

关键词: 血管炎, 肽酰基精氨酸脱亚胺酶4, 抗体, 抗中性白细胞胞质, 支气管炎, 慢性

Abstract: Objective： To investigate the clinical significance of peptidylarginine deiminase type 4 (PAD4) in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). To make a primary observation on the relationship of chronic bronchitis and bronchiectasis (CB) with the pathogenesis of AAV by PAD4. Methods: The sera from 13 patients with AAV, 13 patients with CB, 11 patients with rheumatoid arthritis (RA), 11 patients with primary chronic kidney disease (CKD) and 12 normal controls were collected. Serum PAD4 was detected using commercial ELISA kits. The serum levels of PAD4 were compared not only among the different groups but also between the activity and remission stage of the same disease. The associations between serum PAD4 and the Birmingham Vasculitis Activity Score (BVAS) of AAV were further investigated. Results: (1) The serum levels of PAD4 in patients with AAV, RA and CB at activity stage were all higher than that in the normal controls (P<0.001, respectively, α′=0.007). The serum level of PAD4 in patients with CB at remission stage and that in CKD group were not found elevated compared with the normal controls (P=0.02, P=0.085, respectively, α′=0.007). (2) At activity stage, among the groups of simple AAV, AAV with a long history of CB and CB without AAV, no significant difference was detected. While at remission stage among the 3 groups, the serum level of PAD4 was at the lowest level in CB group without AAV. (3) The serum level of PAD4 in some patients with CB without AAV were found still higher at remission stage. (4) The serum level of PAD4 in AAV with renal damage at activity stage was positively correlated with BVAS (the activity score of AAV, r=0.71, P=0.02). Conclusion: PAD4 is involved in the pathogenesis of AAV. Whether some patients with CB might progress to AAV by the link with PAD4 still need further investigation.

Key words: Vasculitis, Peptidylarginine deiminase type 4, Antibodies, antineutrophil cytoplasmic, Bronchitis, chronic

王增玲, 商进春, 李春梅, 李敏, 邢广群. PAD4在抗中性粒细胞胞浆抗体相关性小血管炎中的作用及意义[J]. 北京大学学报（医学版）, 2014, 46(2): 200-206.

WANG Zeng-Ling, SHANG Jin-Chun, LI Chun-Mei, LI Min, XING Guang-Qun. Significance of serum peptidylarginine deiminase type 4 in ANCA-associated vasculitis[J]. Journal of Peking University(Health Sciences), 2014, 46(2): 200-206.

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