信号识别颗粒抗体相关坏死性肌病的临床及病理研究

发布时间：2018-07-07 12:41

本文选题：信号识别颗粒 + 肌炎特异抗体　；参考：《复旦大学》2014年博士论文

【摘要】：目的分析中国南方人群的肌炎抗体谱,观察并分析信号识别颗粒(signal recognition particle,SRP)抗体相关坏死性肌病患者的临床及肌肉病理表现。方法收集2012年12月至2014年2月就诊于我院的行肌炎抗体谱检测并有明确诊断信息的病例114例,计算肌炎抗体对炎性肌病的灵敏度、特异度及炎性肌病中各肌炎抗体的阳性率。收集其中SRP抗体阳性的炎性肌病共26例患者的临床资料,并随访其治疗及预后,对其中22例患者行肌肉活检,进行苏木精-伊红染色,CD4、CD8、MHC-I、C5b-9、KP-1免疫组织化学染色。分组统计比较急性组(症状达高峰时间≤6m)亚急性组(6m症状达高峰时间≤12m)和慢性组(症状达高峰时间12m)患者的临床表现和肌肉病理表现,分组统计比较病程不同阶段的肌肉病理表现。结果肌炎抗体对炎性肌病的灵敏度为74%,特异度为88%；肌炎特异抗体的灵敏度为52%,特异度为94%；肌炎相关抗体的灵敏度为52%,特异度为94%；SRP抗体(28%)为最常见的肌炎特异抗体,其次为Mi-2抗体(8%)和Jo-1抗体(8%)；Ro-52抗体(41.9%)为最常见的肌炎相关抗体。26例SRP抗体相关坏死性肌病患者性别比女：男=16：10,发病年龄最小16岁,最大62岁,平均42.9+12.1岁。发病季节未见明显集中趋势；症状达高峰的中位时间6.0个月(0.5-24.0个月),最高肌酸激酶(creatine kinase, CK)中位值8704.0U/L(1349.0U/L-14620.0U/L),最差MMT8评分平均53.3+9.9；可见肌肉萎缩(69.2%)、吞咽或构音障碍(46.2%)、肌肉酸痛(46.2%)、肺部间质性病变(50%)、心电图异常(33.3%)、心超异常(37.5%)；22例患者采用两种或以上治疗手段,治疗有效21例(80.8%),难治4例(15.4%),依赖1例(3.8%),男性治疗效果显著差于女性(p=0.014),复发或复燃8例(30.8%)；慢性组病例发病年龄高于急性组(P=0.011)和亚急性组(P=0.024), CK max低于急性组(P=0.014)和亚急性组(P=0.006),最差MMT8评分有高于急性组(P=0.074)和亚急性组(P＝0.155)的趋势,亚急性组的治疗效果差于急性组(P=0.005)；按发展过程可将多数患者的病程分为五个阶段：Ⅰ期(临床前期)、Ⅱ期(发病期)、Ⅲ期(治疗早期)、Ⅳ期(治疗晚期)及V期(缓解期)。肌肉病理总体表现为程度不等的肌纤维的散在变性、坏死和新生、肌纤维大小不等、肌束内结缔组织增多、炎性浸润、MHC-Ⅰ表达上调及C5b-9沉积；病程Ⅲ、Ⅳ期患者肌纤维新生、肌纤维大小不等、肌束内结缔组织增多、C5b-9在非坏死肌纤维膜的沉积显著重于Ⅰ、Ⅱ期(p0.05),肌纤维坏死有轻于Ⅰ、Ⅱ期的倾向(p=0.385), MHC-I表达上调有重于Ⅰ、Ⅱ期的倾向(p=0.093)。随访1例患者Ⅱ、Ⅳ、Ⅴ期分别的SRP抗体结果均为3+,未见该抗体转阴。结论肌炎抗体谱检测在中国南方人群中对炎性肌病有较高的灵敏度和特异度,SRP抗体在中国南方炎性肌病群体中阳性率为28%。SRP抗体相关坏死性肌病的主要临床表现为迅速进展的四肢近端肌无力,肌无力症状重,CK升高明显,肌肉萎缩、消瘦和吞咽或构音障碍较突出；多数患者需要2-3种治疗手段,对治疗多有效但易反复,女性患者治疗效果好于男性；按症状达高峰时间所分的慢性组发病年龄大,肌无力症状和CK升高较轻,亚急性组治疗效果较差；肌肉病理表现为程度不等的肌纤维的散在变性、坏死和新生、肌纤维大小不等、肌束内结缔组织增多、炎性浸润、MHC-I表达上调及C5b-9沉积；随病程发展到后期,肌纤维新生、肌纤维大小不等、肌束内结缔组织增多、MHC-I表达上调和C5b-9在非坏死肌纤维膜的沉积更加明显,而肌纤维散在坏死则开始减少,提示临床病程不同阶段的病理基础。
[Abstract]:Objective to analyze the antibody spectrum of myositis in the southern Chinese population and to observe and analyze the clinical and muscular pathological features of signal recognition particle (SRP) antibody related necrotizing myopathy. Methods 114 cases of anti somatic detection of myositis in our hospital from December 2012 to February 2014 with definite diagnostic information were collected. The sensitivity and specificity of myositis antibody against inflammatory myopathy and the positive rate of antibodies in myositis in myositis were calculated. The clinical data of 26 patients with inflammatory myopathy with positive SRP antibody were collected, and the treatment and prognosis were followed up. 22 of them were performed by muscle biopsy, hematoxylin eosin staining, CD4, CD8, MHC-I, C5b-9, KP-1 immunology Group statistics compared the clinical manifestations and muscle pathological features of acute group (symptom peak time < 6m) subacute group (6m symptom peak time < 12m) and chronic group (symptom peak time 12m), and compare the muscle pathological features at different stages of disease course. Results the sensitivity of myositis antibody to inflammatory myopathy For 74%, the specificity was 88%, the sensitivity of the myositis specific antibody was 52%, the specificity was 94%, the sensitivity of the myositis related antibodies was 52%, the specificity was 94%; the SRP antibody (28%) was the most common myositis specific antibody, followed by the Mi-2 antibody (8%) and the Jo-1 antibody (8%), and the Ro-52 anti body (41.9%) was the most common myositis related antibody in.26 case SRP antibody correlation. The sex ratio of the patients with necrotic myopathy: male =16:10, the age of onset was 16 years old, the maximum 62 years old, the average 42.9+12.1 years old. There was no obvious concentration trend in the onset season; the median time of the peak was 6 months (0.5-24.0 months), the highest level of creatine kinase (creatine kinase, CK) was 8704.0U/L (1349.0U/L-14620.0U/L), and the worst MMT8 score was flat. Both 53.3+9.9, muscle atrophy (69.2%), dysphagia or dysarthria (46.2%), muscle soreness (46.2%), pulmonary interstitial lesions (50%), abnormal electrocardiogram (33.3%) and cardiac abnormal (37.5%); 22 patients were treated with two or more treatments, 21 (80.8%), 4 (15.4%), 1 cases (15.4%), and 1 cases (80.8%)), and the effect of male treatment was significantly worse than that of women. 8 cases (p=0.014), relapse or reignition (30.8%); chronic group cases were higher than acute group (P=0.011) and subacute group (P=0.024), CK Max was lower than acute group (P=0.014) and subacute group (P=0.006), the worst MMT8 score was higher than that in acute group (P=0.074) and subacute group (P = 0.155), and the treatment effect of subacute group was worse than that of acute group (P=0 group) .005); according to the development process, the course of most patients can be divided into five stages: phase I (preclinical), stage II (stage of disease), stage III (early treatment), stage IV (late treatment) and V phase (remission stage). Muscle pathology in general expression of muscle fibers in varying degrees is denatured, necrotic and new, muscle fiber size is different, and connective tissue within the muscle bundle increases. More, inflammatory infiltration, MHC- I expression up and C5b-9 deposition, course III, stage III, stage IV, muscle fiber newborn, muscle fiber size, the increase of connective tissue in the muscle, C5b-9 in the non necrotic muscle fibrous membrane deposition significantly more than I, stage II (P0.05), muscle fiber necrosis is lighter than the tendency of stage I, stage II (p=0.385), MHC-I expression up-regulation is heavier than I, II stage II stage heavier than stage I, stage II stage (stage II) The tendency (p=0.093). The results of the follow-up of 1 patients with SRP antibodies in stage II, IV and V were 3+, and the antibody was detected in the southern Chinese population with high sensitivity and specificity. The positive rate of SRP antibody in the southern inflammatory myopathy group in southern China was 28%.SRP antibody related necrotizing myopathy. The main clinical manifestations are the proximal muscle weakness of the extremities, muscle weakness, muscle weakness, muscle atrophy, muscle atrophy, emaciation and dysphagia or dysarthria. Most patients need 2-3 kinds of treatment, more effective but easy to repeat, and the treatment effect of women is better than that of men; chronic groups divided according to the peak time of symptoms The age was large, myasthenia symptoms and CK increased slightly, and the subacute group was less effective. The muscle pathological manifestations of the muscle fibers were diffuse, necrotic and new, muscle fiber size, connective tissue in the myosus, inflammatory infiltration, MHC-I expression up-regulated and C5b-9 deposition; with the development of the course, muscle fiber newborn, muscle The fiber size was different, the connective tissue in the myocutaneous bundle increased, the expression of MHC-I was up and the deposition of C5b-9 in the non necrotic muscle fibrous membrane was more obvious, while the muscle fiber scattered in the necrosis began to decrease, suggesting the pathological basis of the different stages of the clinical course.
【学位授予单位】：复旦大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R746.1

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