轻链自身抗体在髓过氧化物酶-抗中性粒细胞胞质抗体相关性血管炎肺损害中的意义被引量：4

A preliminary study of the significance of autoantibodies against light chain of myeloperoxidase on pulmonary damages in myeloperoxidase-antineutrophil cytoplasmic antibody associated vasculitis

原文传递

导出

摘要目的初步探讨髓过氧化物酶（MPO）-抗中性粒细胞胞质抗体（ANCA）相关性血管炎（AAV）合并肺损害的临床特点及其与抗MPO轻链ANCA的关系.方法收集195例核周型-ANCA（p-ANCA）及MPO-ANCA均阳性的初诊原发性MPO-AAV患者的临床资料,第3版修订的伯明翰血管炎活动度评分（BVAS-V3）评估病情活动性,使用重组MPO轻链检测MPO轻链ANCA,分析肺损害的特点及其与外周血p-ANCA、MPO-ANCA及MPO轻链ANCA的关系.结果 195例患者中显微镜下多血管炎191例（98.0％）,肉芽肿性多血管炎3例（1.5％）,嗜酸性肉芽肿性多血管炎1例（0.5％）,男64例,女131例,年龄（63.2±13.5）岁.全部患者MPO-ANCA与总BVAS-V3呈正相关（r =0.193,P=0.007）,MPO轻链ANCA与肺BVAS-V3呈正相关（r=0.228;P=0.001）.多系统损害中,肺损害118例（60.51％）,仅次于肾损害（140例,71.80％）.常见肺损害主要为肺浸润80.51％（95/118）、胸腔积液/胸膜炎41.53％（49/118）、肺结节或空洞22.03％（26/118）.有肺损害者较无肺损害者年龄高[（66.39±10.70）岁比（58.30±15.72）岁;t=4.277,P＜0.001]、病程短[2.00（1.00,10.50）个月比3.00（1.00,3.50）个月;Z=-1.604,P=0.109]、总BVAS-V3更高[（18.21±6.08）分比（15.18±5.64）分;t=3.501,P=0.001]、MPO轻链ANCA阳性率明显升高（35.59％比6.49％;x2 =21.569,P＜0.001）、ELISA检测MPO轻链ANCA的吸光度值显著升高（0.377 ±0.229比0.285±0.079;t=3.399,P=0.001）.MPO轻链ANCA阳性者较阴性者肺BVAS-V3明显升高[（4.34±2.10）分比（2.59±2.52）分;=4.301,P＜0.001].结论 MPO-AAV中肺损害常见且多隐匿,ANCA检查及随访对AAV患者肺损害诊断具有重要价值,其中MPO轻链ANCA在AAV肺损害的发病中可能发挥重要作用. Objective To investigate the clinical characteristics of myeloperoxidase （MPO）-antineutrophil cytoplasmic antibody （ANCA） associated vasculitis （MPO-AAV） with pulmonary injury and the relationship between pulmonary injury and ANCA against light chain of MPO （LCMPO-ANCA）.Methods A total of 195 patients with newly diagnosed primary active MPO-AAV were recruited in this prospective study.Indirect immunofiuorescence assay was used to detect peri-nuclear ANCA （p-ANCA）.Immunoblotting and ELISA were used to detect myeloperoxidase-antineutrophil cytoplasmic antibody （MPO-ANCA）.Clinical features of patients with both positive p-ANCA and MPO-ANCA were collected.Disease activity was evaluated by Birmingham Vasculitis Activity Score-version 3 （BVAS-V3） Recombinant light chain of MPO was used to coat substrate of LCMPO-ANCA by ELISA.The clinical characteristics of pulmonary injury and its correlation with serum levels of p-ANCA,MPO-ANCA and LCMPO-ANCA were explored.Results All 195 patients （64 male and 131 female）,consisted of 191 patients （98.0%） with microscopic polyangiitis,3 patients （1.5%） with granulomatosis with polyangiitis,and 1 （0.5%） with eosinophilic granulomatosis with polyangiitis including 64 men and 131 women.Their mean age was （63.2 ±13.5） years old.The level of MPO-ANCA had a positive correlation with general BVAS-V3 （r =0.193,P =0.007） in all patients,and the level of LCMPO-ANCA was positively related with the pulmonary BVAS-V3 （r =0.228,P =0.001）.As for multiple systemic damages,the incidence of lung involvement was 60.51%（118/195）,which ranked second to renal involvement （71.80%,140/195）.The most common pulmonary injuries represented as pulmonary infiltration of 80.51% （95/118）,pleural effusion / pleurisy of 41.53%（49/118）,pulmonary nodule or cavity of 22.03% （26/118）.Compared with those without lung involvement,the patients with pulmonary injuries were older [（66.39 ± 10.70） years old vs （58.30 ±15.72） years old;t =4.277,P =0.001],had a shorter course of disease [2.00（1.00,10.50） months vs 3.00（1.00,3.50） months;t =-2.283,P=0.024],and higher scores of general BVAS-V3 （18.21 ±6.08 vs 15.18 ± 5.64;t =3.501,P =0.001）.Also,in the patients with pulmonary lesions,the positive rate of LCMPO-ANCA was significantly higher （35.59% vs 6.49%;x2 =21.569,P 〈 0.001）,and the level of LCMPO-ANCA was significantly higher （0.377 ±0.229 vs 0.285 ±0.079;t =3.399,P =0.001）than those without lung involvement.The pulmonary BVAS-V3 in the patients with LCMPO-ANCA was significantly higher than that in the patients without LCMPO-ANCA （4.34 ± 2.10 vs 2.59 ± 2.52;t =4.301,P 〈 0.001）,whereas the pulmonary BVAS-V3 was not correlated with LCMPO-ANCA （r =0.035,P =0.708） in patients with lung injuries.Conclusion Pulmonary injury was relatively common and insidious in patients with MPO-AAV.To monitor ANCA level is necessary in patients with pulmonary injury.LCMPO-ANCA might play an important role in the pathogenesis of pulmonary lesions in AAV.

作者张蕾帅宗文胡子盈张铭明陈珊宇

机构地区安徽医科大学第一附属医院风湿免疫科

出处《中华内科杂志》 CAS CSCD 北大核心 2015年第6期511-516,共6页 Chinese Journal of Internal Medicine

基金中华医学会临床医学科研专项资金项目（08010290107）

关键词抗体抗中性粒细胞胞质抗髓过氧化物酶抗体抗髓过氧化物酶轻链抗体血管炎肺损害 Antibodies antineutrophil cytoplasmic Anti-myeloperoxidase antibody Antibody to the light chain of myeloperoxidase Vasculitis Pulmonary damages

分类号 R593.2 [医药卫生—内科学]

作者简介通信作者：帅宗文，Email：shuaizongwen@medmail．com．cn

引文网络
相关文献

参考文献20

1Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides [ J]. Arthritis Rheum, 2013,65 ( 1 ) : 1-11.
2吕远帆,帅宗文,张铭明,胡子盈.髓过氧化物酶-抗中性粒细胞胞质抗体相关性血管炎132例临床分析[J].中华风湿病学杂志,2014,18(5):308-312. 被引量：25
3Xu PC, Chen M, Zhao MH. Antineutrophil cytoplasmic autoantibody-associated vasculitis in Chinese patients [ J ] . Clin Exp Nephrol, 2013,17(5) :705-707.
4Chert M, Yu F, Zhang Y, et al. Clinical [ corrected ] and pathological characteristics of Chinese patients with antineutrophil cytoplasmic antoantibody associated systemic vasculifides: a study of 426 patients from a single centre [ J ]. Postgrad Med J, 2005,81 (961) :723-727.
5Homma S, Suzuki A, Sato K. Pulmonary involvement in ANCA- associated vasculitis from the view of the pulmonologist [ J ]. Clin Exp Nephrol, 2013,17 ( 5 ) : 667-671.
6Arimura Y, Kawashima S, Yoshihara K, et al. The role of myeloperoxidase and myel cytoplasmic antibodies (MPO-ANCAs) in the pathogenesis of human MPO- ANCA-associated glomerulonephritis [ J ] . Clin Exp Nephrol, 2013,17 (5) :634-637.
7Gou SJ, Xu PC, Chen M, et al. Epitope analysis of anti- myeloperoxidase antibodies in patients with ANCA-associated vasculitis[ J]. PLoS One, 2013,8(4) :e60530.
8Roth A J, Ooi JD, Hess JJ, et al. Epitope specificity determines pathogenicity and detectability in ANCA-associated vasculitis [ J ]. J Clin Invest, 2013,123 (4) :1773-1783.
9Leavitt RY, Fauci AS, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis [ J ]. Arthritis Rheum, 1990,33 ( 8 ) : 1101-1107.
10Masi AT, Hunder GG, Lie JT, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiifis ) [ J ]. ArthritisRheum, 1990,33 ( 8 ) : 1094-1100.

二级参考文献20

1Jennette JC,Falk RJ,Bacon PA,et al.2012 revised international Chapel Hill consensus conference nomenclature of vasculitides[J].Arthritis Rheum,2013,65:1-11.
2Reinhold-Keller E,Herlyn K,Wagner-Bastmeyer R,et al.Stable incidence of primary systemic vasculitides over five years:results from the German vasculitis register[J].Arthritis Rheum,2005,53:93-99.
3Fujimoto S,Watts RA,Kobayashi S,et al.Comparison of the epidemiology of anti-neutrophil cytoplasmic antibody-associated vasculitis between Japan and the U.K[J].Rheumatology (Oxford),2011,50:1916-1920.
4Chen M,Yu F,Zhang Y,et al.Clinical[corrected]and pathological characteristics of Chinese patients with antineutrophil cytoplasmic autoantibody associated systemic vasculitides:a study of 426 patients from a single centre[J].Postgrad Med J,2005,81:723-7.
5Oh JS,Lee CK,Kim YG,et al.Clinical features and outcomes of microscopic polyangiitis in Korea[J].J Korean Med Sci,2009,24:269-274.
6Ahn JK,Hwang JW,Lee J,et al.Clinical features and outcome of microscopic polyangiitis under a new consensus algorithm of ANCA-associated vasculitides in Korea[J].Rheumatol Int,2012,32:2979-2986.
7Roth A J,Ooi JD,Hess J J,et al.Epitope specificity determines pathogenicity and detectability in ANCA-associated vasculitis[J].J Clin Invest,2013,123:1773-1783.
8Xiao H,Heeringa P,Hu P,et al.Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomeru lonephritis and vasculitis in mice[J].J Clin Invest,2002,110:955-963.
9Little MA,Smyth CL,Yadav R,et al.Antineutrophil cytoplasm antibodies directed against myeloperoxidase augment leukocyte microvascular interactions in vivo[J].Blood,2005,106:2050-2058.
10Leavitt RY,Fauci AS,Bloch DA,et al.The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis[J].Arthritis Rheum,1990,33:1101-1107.