血清抗氨酰tRNA合成酶抗体检测在特发性炎性肌病伴间质性肺疾病中的意义

目的 检测多发性肌炎/皮肌炎患者血清抗氨酰tRNA合成酶(ARS)抗体水平,并与抗Jo-1抗体相比较,探讨其在特发性炎性肌病伴间质性肺疾病(ILD)中的意义.方法 采用酶联免疫吸附试验(ELISA)法测定109例多发性肌炎/皮肌炎患者,20例系统性红斑狼疮(SLE)患者,20例类风湿关节炎(RA)患者以及30名健康对照组血清中抗ARS抗体水平及阳性率.使用t检验、Mann-Wittney U检验、X2检验及Fisher精确检验分析ARS阳性患者的临床特点.使用McNemar检验比较抗ARS抗体和抗Jo-1抗体对诊断多发性肌炎/皮肌炎合并ILD的敏感性及特异性.结果 血清抗ARS抗体的阳性率在合并ILD的多发性肌炎/皮肌炎组、未合并ILD的多发性肌炎/皮肌炎组、SLE组、RA组及健康对照组分别是37.9％、7.8％、10％、0和0.合并ILD的多发性肌炎/皮肌炎组血清抗ARS抗体阳性率较未合并ILD的多发性肌炎/皮肌炎组、SLE组、RA组和健康对照组均显著升高(X2-13.5,5.45,10.57,15.17;P＜0.01).抗ARS抗体诊断多发性肌炎/皮肌炎合并ILD的敏感性显著高于抗Jo-1抗体(37.9％比17.2％,P＜0.01),而两者特异性差异无统计学意义(P＞0.05).抗ARS抗体阳性患者发热、ILD发生率较抗ARS抗体阴性患者显著升高(X2=12.55,13.53;均P＜0.01),而披肩征及向阳疹的发生率则低于ARS阴性组(X2=5.7,5.8;P均＜0.05).抗ARS抗体阳性组同抗Jo-1抗体阳性组间临床特点差异无统计学意义(P均＞0.05).随访发现多发性肌炎/皮肌炎合并ILD死亡患者血清抗ARS抗体均为阴性.结论 相较抗Jo-1抗体而言,血清抗ARS抗体检测对多发性肌炎/皮肌炎伴ILD的诊断敏感性更高,有利于早期诊断,值得临床推广应用.     

多发性肌炎和皮肌炎血清抗Jo-1抗体水平与疾病活动度相关性研究

目的 探讨抗Jo-1抗体水平与多发性肌炎/皮肌炎疾病活动度的相关性.方法 采用免疫印迹法和酶联免疫吸附试验(ELISA)法检测148例多发性肌炎/皮肌炎患者和性别年龄相匹配的130名健康人血清抗Jo-1抗体水平,利用国际肌炎组织制定的炎性肌病评价工具评估抗Jo-1抗体阳性患者疾病活动度(VAS),并分析抗Jo-1抗体水平与多发性肌炎肢肌炎疾病活动度的相关性.统计学处理采用x2检验或t检验.结果 免疫印迹法和ELISA法检测多发性肌炎/皮肌炎患者血清抗Jo-1抗体的阳性率分别是24.3％(36/148)和27.0％(40/148),健康人血清中抗Jo-1抗体均为阴性.发热、肺间质病变(ILD)和关节炎/关节痛在抗Jo-1抗体阳性组的比例明显高于抗Jo-1抗体的阴性组(P＜0.05).抗Jo-1抗体阳性患者的总疾病活动度评分与血清抗Jo-1抗体的浓度呈正相关(r=0.874,P=0.000).7例患者治疗后患者血清抗Jo-1抗体浓度与疾病活动度评分均显著下降,两者变化一致.结论 ELISA法检测抗Jo-1抗体水平与疾病活动相关,可作为多发性肌炎/皮肌炎疾病活动的评价指标.     

多发性肌炎/皮肌炎患者外周血淋巴细胞亚群检测的临床应用价值

目的 探讨外周血淋巴细胞亚群异常在多发性肌炎和皮肌炎中的临床意义.方法 用流式细胞仪检测89例多发性肌炎／皮肌炎患者外周血淋巴细胞标记分子的表达情况,分析淋巴细胞亚群变化与疾病临床特点之间的关系.采用方差分析,独立样本t检验,x2检验及多因素Logistic回归分析进行统计学处理.结果 外周血CD3+、CD3+CD4+和CD3+CD8+细胞计数在初治并处于活动期的皮肌炎患者[分别为(8±4),(5.4±2.8)和(2.6±1.6)×108/L]明显低于非活动期皮肌炎患者[(16±6),(10.4±5.6)和(5.6±3.8)×108/L]和健康对照[(14±4),(8.3±2.8)和(4.6±1.7) ×108/L)](F=12.901,8.257,7.084;P值均＜0.05),活动期和非活动期的皮肌炎患者CD19+CD5-细胞百分比[分别为( 13.9±8.3)％和(14.2±7.0)％)]则明显高于健康对照[(6.9±2.1)％],差异具有统计学意义(F=21.443;P值均＜0.05).多因素Logistic回归分析发现,多发性肌炎/皮肌炎患者肌炎活动视觉模拟评估工具.疾病总活动度评分是患者外周血CD3+.CD3+CD4和CD3+CD8细胞计数减低的独立影响因素(b值=0.211,0.344,0.289;P值均＜0.05);多发性肌炎,皮肌炎合并间质性肺疾病(ILD)是CD3+细胞计数减低及CD3+CD4+细胞百分比减低的独立影响因素(b值=0.928,1.974;P值均＜0.05).另外Logistic回归分析发现.CD3+CD8+细胞数减低是多发性肌炎,皮肌炎死亡的独立危险因素(b值=-0.011,OR=0.989; P＜0.05).结论 外周血淋巴细胞亚群在多发性肌炎,皮肌炎疾病活动期明显异常,合并ILD可能影响部份外周淋巴细胞亚群的数量,而CD8+T细胞计数明显降低的患者死亡危险将增加.淋巴细胞亚群检测结果对临床评估多发性肌炎,皮肌炎病情活动及预后有重要指导意义.     

抗黑色素瘤分化相关基因5抗体对皮肌炎合并快速进展性间质性肺病预后的影响

目的 分析抗黑色素瘤分化相关基因5(MDA5)抗体阳性皮肌炎患者临床特征及抗体滴度对快速进展性间质性肺病(RPILD)预后的影响。方法 回顾性分析南京医科大学炎性肌病及结缔组织病相关间质性肺病专病联盟所收集的352例皮肌炎患者的临床资料，其中抗MDA5抗体阳性组249例，抗MDA5抗体阴性组103例，比较两组的临床特点及实验室指标。采用Kendall′s W相关分析抗MDA5抗体滴度与RPILD发生率及死亡率的相关性，采用Logistic回归分析抗MDA5抗体滴度对预后的风险变化，生存分析采用Kaplan-Meier法。结果 抗MDA5抗体阳性组皮疹、技工手、关节炎及间质性肺病(ILD)较抗MDA5抗体阴性组更常见，而抗MDA5抗体阴性组肌无力更明显，差异有统计学意义(P<0.001)。与抗MDA5抗体阴性组比较，抗MDA5抗体阳性组谷草转氨酶(AST)、血沉(ESR)、血清铁蛋白(SF)水平及抗Ro52抗体阳性率均较高，而乳酸脱氢酶(LDH)及肌酸激酶(CK)水平较低，两组之间差异有统计学意义(均P<0.05)。抗MDA5抗体阳性滴度与RPILD的发生率存在相关性(r=0...     

男性抗黑色素瘤分化相关基因5抗体阳性皮肌炎患者临床特征及预后分析

目的探讨男性抗黑色素瘤分化相关基因5(MDA5)抗体阳性皮肌炎患者临床特征及预后不良因素。方法回顾性分析江苏省肌炎协作组2017—2020年间住院246例抗MDA5抗体阳性的皮肌炎患者的临床资料。计数资料组间比较采取χ2检验;定量资料采用M(Q1, Q3)表示, 组间比较采用秩和检验;单因素生存分析采用Kaplan-Meier法和Log-rank检验;多因素生存分析采用Cox比例风险模型;以P<0.05为差异有统计学意义。结果①男性抗MDA5抗体阳性患者向阳疹[67.1%(47/70)与52.8%(93/176), χ2=4.18, P=0.041]、V字征比例高于女性组[50.0%(35/70)与30.7%(54/176), χ2=8.09, P=0.004], 男性组CK[112(18, 981)U/ml与57(13.6, 1 433)U/ml, Z=-3.50, P<0.001]及血清铁蛋白(SF)水平[1 500(166, 32 716)ng/ml与569(17.8, 14 839)ng/ml, Z=-5.85, P<0.001]高于女性组;男性组ESR[31...     

磁共振成像在多发性肌炎和皮肌炎治疗评价中的初探

目的 探讨多发性肌炎和皮肌炎治疗前后磁共振成像( MRI)检查的价值.方法 纳入15例多发性肌炎及皮肌炎患者,治疗前后分别行患者双下肢近端肌群MRI检查,检测血清肌酸激酶水平,并测定肌力;对比治疗前后肌力与MRI结果之间、肌力与肌酸激酶之间的相关性.统计学处理采用独立样本t检验及Pearson相关分析.结果 治疗前患者MR[计分2.37±0.62,肌酸激酶(3841±3175) U/L,肌力评分15.1±2.4;治疗后MRI计分1.30±0.28,肌酸激酶(549±338) U/L,肌力评分18.1±0.9,差异有统计学意义(P＜0.05).肌力与MRI计分、肌酸激酶水平均有相关性,且与前者呈强相关(r=-0.890,P＜0.05).结论 MRI能更好地反映多发性肌炎及皮肌炎患者肌力改善情况,较血清肌酸激酶有更高的敏感性.     

女性结缔组织病患者瘦素及可溶性受体的变化和意义

目的 探讨瘦素及其可溶性受体在女性结缔组织病(红斑狼疮、皮肌炎/多发肌炎及硬皮病)患者中的变化和意义.方法 采用放射免疫分析法及酶联免疫吸附试验(ELISA)分别检测红斑狼疮、皮肌炎/多发肌炎及硬皮病患者血清中瘦素及可溶性受体水平并与正常对照组比较.结果 盘状红斑狼疮、限局性硬皮病患者血清瘦素及其可溶性受体水平与正常对照组相比,差异无统计学意义(P＞0.05):与正常对照组相比,系统性红斑狼疮患者血清瘦素水平明显升高,差异有统计学意义(P＜0.01),皮肌炎/多发肌炎、系统性硬皮病患者血清瘦素水平明显降低,差异有统计学意义(P＜0.01).与正常对照组相比,系统性红斑狼疮、皮肌炎/多发肌炎及系统性硬皮病患者可溶性受体水平明显降低,差异有统计学意义(P＜0.01).结论 系统性红斑狼疮、皮肌炎/多发肌炎及系统性硬皮病患者体内存在瘦素及其受体水平的异常,这种异常可能与其发病有关.     

特发性炎性肌病分型诊断标准的比较分析

目的 评价Bohan/Peter标准(B/P标准)与欧洲神经肌肉疾病中心(ENMC)标准对特发性炎性肌病分型诊断皮肌炎和多发性肌炎的准确性.方法 回顾性收集86例初诊为特发性炎性肌病患者的临床、实验室及骨骼肌病理资料,分别用B/P标准与ENMC标准进行分型诊断,比较两个标准诊断皮肌炎和多发性肌炎的异同性.数据分析采用SPSS 13.0软件系统进行非参数检验(Mann Whitney U检验)和一致性检验(Kappa分析)方法.结果 B/P标准诊断皮肌炎37例,多发性肌炎49例;ENMC标准诊断皮肌炎46例,多发性肌炎仅14例,其余为嗜酸细胞性肌炎1例、疑诊散发性包涵体肌炎9例,未能分型者5例,肢带型肌营养不良2B型11例.Kappa分析检验两个标准诊断皮肌炎一致性较好(κ=0.79),诊断多发性肌炎一致性差(κ=0.26).结论 B/P标准对多发性肌炎存在过度诊断、误诊风险.ENMC标准纳入免疫病理,增加了临床与病理诊断的排除标准,其分型诊断准确性优于B/P标准.     

多发性肌炎/皮肌炎患者外周血Ⅰ型干扰素诱导趋化因子的临床意义

目的探讨Ⅰ型干扰素诱导趋化因子在多发性肌炎/皮肌炎的表达及与临床特征相关性。方法实时定量PCR检测52例多发性肌炎(polymyositis, PM)/皮肌炎(dermatomyositis, DM)患者及20名健康对照组(health donors, HD)PBMCs中5个经典的Ⅰ型干扰素趋化因子诱导基因:单核细胞趋化蛋白-1(monocyte chemotactic protein 1, MCP-1)、干扰素诱导蛋白10(interferon-inducible protein-10, IP-10)、重组人干扰素诱导T细胞趋化物(interferon-inducible T cell alpha chemoattractant,I-TAC)、单核细胞趋化蛋白-2(monocyte chemotactic protein 2, MCP-2)、人巨噬细胞炎性蛋白1α(macrophage inflammatory protein1α, MIP-1α),计算趋化因子积分,并与相应临床资料进行统计学分析。组间比较采用Mann-Whitney检验,相关性分析采用Spearman检验。结果多发性肌炎/皮肌炎组PBMC上述趋化因子的mRNA水平均明显高于健康对照组:MCP-1[180.4(54.1,501.1)比16.4(0.8,27.8)]、IP-10[320.4(104.8,534.7)比24.1(0.9,31.4)]、I-TAC[48.4(25.4,144.7)比24.1(3.6,31.3)]、MCP-2[201.6(104.3,658.7)比24.6(2.8,32.8)]、MIP-1α[168.3(110.4,527.6)比21.5(0.8,31.4)](Z=-4.775,-4.676,-4.479,-4.298,-5.022;P0.0001)。且趋化因子积分在多发性肌炎/皮肌炎患者中显著增高[48.4(25.4,144.7)比2.2(0.6,4.0),Z=-5.630,P0.01]。同一患者,与稳定期相比,疾病活动期的趋化因子积分显著升高(P0.05)。结论 MCP-1、IP-10、I-TAC、MCP-2、MIP-1α的mRNA水平在多发性肌炎/皮肌炎患者PBMC中表达明显增高,趋化因子积分可能是反映多发性肌炎/皮肌炎活动的生物学标志物。     

多发性肌炎/皮肌炎自身抗体检测及血清肌酶变化的观察

对55例临床确诊为多发性肌炎/皮肌炎(PM/DM)患者,进行抗核抗体(ANA)、抗细胞浆抗体(ACYA)、抗JO-1抗体及血清肌酶检测.发现PM/DM患者ANA、ACYA、抗JO-1抗体表达均明显高于正常对照组;PM/DM患者血清肌酸激酶、α-羟丁酸脱氢酶、乳酸脱氢酶和天冬氨酸氨基转移酶水平均明显高于对照组.认为ANA、ACYA、抗JO-1抗体及血清肌酶的检测对提高该疾病的诊断、指导治疗及预后均具有重要意义.     

多发性肌炎/皮肌炎合并间质性肺疾病的相关因素及预后不良因素分析

目的 探讨多发性肌炎/皮肌炎(PM/DM)患者发生间质性肺疾病(ILD)的相关因素及影响预后的不良因素.方法 以上海第二军医大学长海医院1997年1月至2006年11月收住的PM/DM患者87例为研究对象,分为ILD组40例(男13例,女27例),平均年龄(54±13)岁;非ILD组47例(男25例,女22例),平均年龄(45±18)岁.对ILD的发生率、临床特征和预后进行分析.正态分布的计量资料采用t检验,偏态分布的计量资料采用秩和检验,计数资料两组率的比较采用x2检验,PM/DM伴发ILD的预测因素和预后不良因素采用logistic回归分析和Kaplan-Meier生存曲线.结果 PM/DM中ILD的发生率为46％(40/87),病死率为40％(16/40).ILD组的平均年龄[(54±13)岁]明显大于非ILD组[(45±18)岁];ILD组出现发热(21/40)、吞咽困难(16/40)、关节痛(26/40)、Gottron皮疹(14/40)和心脏损害(26/40)的百分率明显高于非ILD组(分别为7/47、8/47、9/47、2/47和14/47);ILD组的血清乳酸脱氢酶[(472±285)IU]和ESR[(44 ±24)mm/1 h]明显高于非ILD)组[(310±238)IU和(26±24)mm/1 h];ILD组的IgG[(18±9)g/L]明显高于非ILD组[(14±5)g/L].经多因素非条件logistic回归分析,筛选出4个与ILD相关的预测因子:Gottron皮疹、关节痛、发热和年龄≥40岁,其相对危险度分别为12.048、7.812、6.329和5.236;生存分析结果显示,Gottron皮疹、心脏损害和肺间质病变是影响ILD预后的不良因素.结论 PM/DM患者年龄≥40岁,出现Gottron皮疹、关节痛和发热与ILD的发生密切相关,Gottron皮疹、心脏损害和肺间质病变是影响ILD预后的不良因素.     

Anti-MDA5 antibody is associated with A/SIP and decreased T cells in peripheral blood and predicts poor prognosis of ILD in Chinese patients with dermatomyositis

The aim of this study is to determine serum anti-melanoma differentiation-associated gene 5 prevalence and their clinical associations in Chinese patients with polymyositis and dermatomyositis (PM/DM). Serum anti-MDA5 antibody was detected by ELISA in 113 adult PM/DM patients and in various controls. Flow cytometry was applied to analyze the subgroups of lymphocytes in the peripheral blood of PM/DM patients. The serum anti-MDA5-positive rate in the DM patients (22.6%) was significantly higher compared with that in PM patients (0%, P?<?0.005), patients with SLE (3.3%, P?<?0.05), RA (3.3%, P?<?0.05), pSS (0%, P?<?0.05), pulmonary infection (0%, P?<?0.05) and healthy controls (0%, P?<?0.001). The percentage of decreased CD4⁺, CD8⁺ T cell counts, raised CD4⁺/CD8⁺ ratio in peripheral blood and the incidence of acute/subacute interstitial pneumonia (A/SIP) were significantly higher in anti-MDA5-positive DM group than negative group (all P?<?0.05). Additionally, logistic multivariate analysis showed that anti-MDA5 is an independent risk factor for death of ILD in DM (OR?=?8.46, 95% CI 1.77?C40.36, P?=?0.007). In conclusion, in Chinese PM/DM patients, serum anti-MDA5 antibody is mainly presented in DM patients and can be a useful marker for A/SIP in patients with DM. It can predict unfavorable prognosis in DM patients with ILD. Further studies are needed to identify how the abnormal T cells in peripheral blood participated in the generation of the anti-MDA5 antibody.     

Serum ferritin correlates with activity of anti-MDA5 antibody-associated acute interstitial lung disease as a complication of dermatomyositis

Dermatomyositis (DM) is occasionally complicated by interstitial lung disease. Acute/subacute interstitial pneumonia (A/SIP) with DM is intractable and life threatening. Clinically amyopathic dermatomyositis (C-ADM) is also reported to be complicated with A/SIP, especially in those patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody. In the present cases, we indicate that serum ferritin level correlated with activity of A/SIP with DM. Two patients, a 65-year-old woman and a 30-year-old woman, were diagnosed with anti-MDA5 antibody-associated A/SIP with DM. Serum ferritin was high, 1600 and 770 mg/dl, respectively, on admission. Immunosuppressive therapy ameliorated A/SIP in both cases. Similarly, serum ferritin was also decreasing. However, A/SIP was recurrent and progressive, and serum ferritin was also increasing again in one case. In conclusion, serum ferritin correlates with disease activity of anti-MDA5 antibody-associated A/SIP with DM. Intensity of treatment may be decided according to serum ferritin level.     

Serum ferritin correlates with activity of anti-MDA5 antibody-associated acute interstitial lung disease as a complication of dermatomyositis

Abstract

Dermatomyositis (DM) is occasionally complicated by interstitial lung disease. Acute/subacute interstitial pneumonia (A/SIP) with DM is intractable and life threatening. Clinically amyopathic dermatomyositis (C-ADM) is also reported to be complicated with A/SIP, especially in those patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody. In the present cases, we indicate that serum ferritin level correlated with activity of A/SIP with DM. Two patients, a 65-year-old woman and a 30-year-old woman, were diagnosed with anti-MDA5 antibody-associated A/SIP with DM. Serum ferritin was high, 1600 and 770 mg/dl, respectively, on admission. Immunosuppressive therapy ameliorated A/SIP in both cases. Similarly, serum ferritin was also decreasing. However, A/SIP was recurrent and progressive, and serum ferritin was also increasing again in one case. In conclusion, serum ferritin correlates with disease activity of anti-MDA5 antibody-associated A/SIP with DM. Intensity of treatment may be decided according to serum ferritin level.     

多发性肌炎/皮肌炎合并间质性肺疾病预测因素的Meta分析

目的 系统分析和评价多发性肌炎/皮肌炎合并间质性肺疾病的预测因素,为临床早期诊治提供循证依据。方法 利用Meta分析方法分析国内外23篇关于多发性肌炎(PM)/皮肌炎合并间质性肺疾病( ILD)预测因素的文献,应用Rev-Man 4.2分析软件进行异质性和敏感性分析,并根据异质性检验结果,采用固定效应或随机效应模型计算合并比值比（OR值）和95％可信区间(95％CI)。应用Stata 10.0软件进行发表偏倚识别。结果 对关节炎/关节痛、发热、抗Jo-1抗体阳性、抗核抗体阳性、Gottron征、吞咽困难、雷诺现象共7个因素进行Meta分析,结果显示与PM/皮肌炎合并ILD存在关联性的因素及其OR值和95％CI分别是：抗Jo-1抗体阳性6.94(4.74～10.16)、发热4.90( 3.82～6.29)、关节炎/关节痛3.93(3.21～4.80)、Gottron征2.52(1.24～5.14)和抗核抗体阳性1.59( 1.02～2.47)。而与PM/皮肌炎合并ILD无关联性的因素及其OR值和95％CI分别为雷诺现象1.40(0.97～2.01)和吞咽困难1.21 (0.94～1.56)。结论 抗Jo-1抗体阳性、发热、关节炎/痛、Gottron征和抗核抗体阳性可作为PM/皮肌炎合并ILD的主要预测因素。     

Limitations of a single-point evaluation of anti-MDA5 antibody, ferritin, and IL-18 in predicting the prognosis of interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis

Autoantibodies against melanoma differentiation-associated gene 5 (MDA5) are important serological markers in dermatomyositis (DM) with rapidly progressive interstitial lung disease (ILD). Recent studies noted that anti-MDA5 antibody (anti-MDA5ab), ferritin, and IL-18 are useful biomarkers for evaluating the responses to treatment and the status of ILD in anti-MDA5ab-positive DM. In this study, we further studied the importance of anti-MDA5ab levels and of ferritin and IL-18 concentrations in our patients. These biomarkers could be sometimes useful for evaluating ILD status and/or predicting the prognosis in patients with anti-MDA5ab-positive DM with several exceptional cases. A single-point evaluation of anti-MDA5ab levels and of ferritin and IL-18 concentrations has limitations in predicting the prognosis of ILD with DM. We consider that the timing of initial therapy and the anti-MDA5ab isotype, in addition to the patient’s age, are also crucial factors for predicting the prognosis.     

Neutrophil extracellular traps may contribute to interstitial lung disease associated with anti-MDA5 autoantibody positive dermatomyositis

In dermatomyositis (DM), anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody (autoAb) marks a subtype with low grade or absent muscle inflammation but frequent and rapidly progressive interstitial lung disease (ILD). The pathogenesis of ILD remains poorly unknown. The aim of the study is to explore whether neutrophil extracellular traps (NETs) are involved in the development of ILD in DM patients with anti-MDA5 autoAb. Patients with clinically amyopathic dermatomyositis (CADM, n = 20), classic dermatomyositis (cDM, n = 30), polymyositis (PM, n = 20), and healthy controls (HC, n = 20) were enrolled. Anti-MDA5 autoantibody and Krebs von den Lungen-6 (KL-6) were detected by ELISA. Circulating levels of NETs were assessed by the quantification of both serum cell-free DNA (cfDNA) and LL-37 (cathelicidin LL-37). Immunofluorescent staining was used to visualize NETs ex vivo. The elevated circulating NETs level was detected in DM patients with ILD complication. Compared to anti-MDA5 Ab^? DM patients, anti-MDA5 Ab⁺ DM patients had the higher concentrations of serum cfDNA (293 ± 69 vs 252 ± 63 ng/ml; P = 0.035) and serum LL-37 (0.6 ± 1.0 vs 0.2 ± 0.2 ng/ml; P = 0.026). Positive correlations were established between serum levels of cfDNA and KL-6 in DM patients (r _s = 0.4422, P = 0.0003). anti-MDA5 Ab⁺ sera, other than anti-MDA5 Ab^? sera, could induce greater numbers of normal neutrophils to form NETs in vitro. These data suggest that aberrant NETs formation may be involved in the pathogenesis of ILD in DM patients with anti-MDA5 autoAb.     

Comparison of radioimmunoprecipitation versus antigen-specific assays for identification of myositis-specific autoantibodies in dermatomyositis patients

Abstract

Background. To confirm the antigen specificities of autoantibodies that precipitate 140-kDa (anti-p140) or 155/140-kDa polypeptides (anti-p155/140) previously identified by radioimmunoprecipitation in Korean patients with dermatomyositis (DM) and to look into the relationship between each MSA and clinical features of DM.

Methods. Seventeen serum samples of classic DM patients who had been found to have either anti-p140 antibodies (n = 9) or anti-p155/140 (n = 8) antibodies in our previous study were examined using enzyme-linked immunosorbent assay (for anti-MDA5 antibodies) and immunoblotting (for anti-MJ/NXP-2 and anti-TIF-1γ antibodies).

Results. Seven out of nine anti-p140 antibody positive patients were found to have anti-MDA5 antibodies. Two out of nine had anti-MJ/NXP-2 antibodies with no interstitial lung disease (ILD). All eight anti-p155/140 antibody positive patients were found to have anti-TIF-1γ antibodies. Anti-TIF-1γ and anti-MDA5 antibodies were simultaneously detected in one patient with anti-p155/140 antibody, who suffered HIV infection and non-Hodgkin's lymphoma. The associations between anti-MDA5 antibody and rapidly progressive ILD and between anti-TIF-1γ antibody and cancer-associated DM were confirmed to be significant.

Conclusions. Although radioimmunoprecipitation still looks to be a good screening tool, confirmation with antigen-specific assays seems mandatory. The associations between anti-MDA5 and rapidly progressive ILD and between anti-TIF-1γ and cancer-associated DM were confirmed in Korean patients with DM.     

Clinical significance of serum surfactant protein D (SP-D) in patients with polymyositis/dermatomyositis: correlation with interstitial lung disease

OBJECTIVE: To determine the clinical significance of serum surfactant protein D (SP-D) levels in patients with polymyositis/dermatomyositis (PM/DM). METHODS: Serum SP-D levels were assayed using a sensitive enzyme-linked immunosorbent assay in 59 patients with PM/DM and in 29 healthy controls. RESULTS: The serum level of SP-D was significantly higher in patients with PM/DM than in healthy controls (mean+/-S.D. 61.7+/-122.6 vs 31.0+/-12.4 ng/ml, P < 0.01). The serum SP-D level in patients with interstitial lung disease (ILD) was significantly higher than in those without ILD (118.7+/-220.2 vs 38.7+/-21.0 ng/ml, P < 0.001). Serum level of SP-D was correlated with the presence of ILD. The incidences of decreased vital capacity (%VC) and of decreased diffusing capacity of carbon monoxidase (%DLCO) were also significantly greater in patients with an elevated SP-D level than in those with a normal level (64 vs 7%, P < 0.02; 73 vs 27%, P < 0.01). Moreover, the serum SP-D level was inversely correlated with %VC (r=-0.452, P < 0.01) and %DLCO (r=-0.349, P < 0.05). CONCLUSION: The serum SP-D level may be a useful marker for ILD in patients with PM/DM.     

Anti-MDA5 antibody, ferritin and IL-18 are useful for the evaluation of response to treatment in interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis

Objective. The aim of this study was to investigate the precise clinical characteristics and to analyse the association between the anti-MDA5 antibody (anti-MDA5ab) titre and disease status in patients with anti-MDA5ab-positive DM. Methods. Twenty-seven patients who presented with DM and were positive for the anti-MDA5ab were enrolled. The association between the clinical manifestations and the clinical parameters, including the anti-MDA5ab, was analysed. Results. The complication of rapidly progressive interstitial lung disease (RP-ILD) occurred in 20 (74%) patients. The frequencies of fatal outcome, relapse and malignancy were 33, 4 and 4%, respectively. Remarkably, a fatal outcome occurred within the first 6 months. Compared with six non-RP-ILD patients, elderly age at onset, severely involved pulmonary function and high levels of serum ferritin were present in 20 RP-ILD patients with anti-MDA5ab. Alveolar-arterial oxygen difference (AaDO(2)) ≥32?mmHg and ferritin ≥828?ng/ml at admission were poor prognostic factors in RP-ILD patients with anti-MDA5ab-positive DM. The median value of the anti-MDA5ab titre on admission was higher in patients who later died than in those who survived. The efficacy of treatment was indicated by the anti-MDA5ab, ferritin and IL-18 concentrations. The decline index of the anti-MDA5ab titre after treatment was lower in the subset of patients who died than in the subset of patients who lived. Sustained high levels of anti-MDA5ab, ferritin and IL-18 were present in the patients who died. Conclusion. Anti-MDA5ab titre and ferritin and IL-18 concentrations are useful for the evaluation of the response to treatment and the status of ILD in patients with anti-MAD5ab-positive DM.