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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。
OBJECTIVE: To investigate the effect of peptidylarginine deiminase type 4 (PAD4) on ANCA-associated vasculitis (ANCA) -associated vasculitis (AAV) The pathogenesis and clinical significance of disease activity, and the relationship between chronic bronchitis and AAV to do a preliminary discussion. Methods Thirteen patients with AAV, 13 patients with chronic bronchitis and bronchiectasis (CB) and 11 patients with rheumatoid arthritis (RA) during the onset and remission stage were enrolled in this study. Serum from patients with primary kidney disease (CKD) and 12 healthy controls. The levels of PAD4 in serum were detected by ELISA. The differences of PAD4 expression in different groups were compared. The correlation between PAD4 and Birmingham Vasculitis Activity Score (BVAS) was further studied. Results: (1) The levels of PAD4 in AAV group, RA group and attacking CB group were significantly higher than those in normal control group (P <0.001, α ’= 0.007) during the attack and remission stages, while in remission stage (P = 0.02, P = 0.085, α ’= 0.007, respectively) in patients with CKD and in CKD patients, the level of PAD4 was not significantly different from the normal controls. (2) There was no significant difference in the PAD4 levels between the AAV group, the AAV group and the CB group during the attack period, but the PAD4 level in the CB group was the lowest during the remission period. (3) PAD4 in some CB patients still maintained a high level during remission. (4) The level of PAD4 in patients with AAV renal impairment was positively correlated with BVAS score (r = 0.71, P = 0.02). Conclusion: PAD4 is involved in the development of AAV. Some patients with chronic bronchitis have a certain correlation with the pathogenesis of AAV.