我国成人多发性肌炎/皮肌炎患者临床特征谱、器官损害相关因素及血清标志物探讨和炎症体在发病机制中作用的研究
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摘要
目的：成人多发性肌炎(polymyositis, PM)和皮肌炎(dermatomyositis,DM)属于特发性炎性肌病,是一组可损害骨骼肌、皮肤及多种脏器的全身性自身免疫性疾病。PM/DM伴器官损害是影响疾病预后的重要因素。本课题拟：1)组织我国最大规模的关于PM/DM的多中心回顾性研究,总结分析成人PM/DM临床表现及主要器官损害的发生率和特点,确定与其相关的特异性因素；2)探讨基质金属蛋白酶-9降解工Ⅲ型胶原蛋白的降解产物(C3M)与PM/DM患者合并间质性肺病(interstitial lung disease, ILD)及主要临床指标的相关性,评价其是否可以作为PM/DM患者合并ILD的血清学诊断指标。3)从固有免疫角度探讨炎症体在此类疾病发病机制中的作用。
对象和方法：本研究分为三部分：第一部分使用统一的调查表,回顾性收集所有于2007-2012年间在全国22个三级甲等医院风湿免疫科住院的符合纳入排除标准的1387例成人PM/DM患者的病例资料,并进行多因素logistic回归分析；第二部分采用酶联免疫吸附法检测46例成人PM/DM(30例合并ILD,15例不合并ILD)和19例正常对照血清C3M浓度,用ROC曲线分析C3M的诊断价值,并统计分析C3M与主要临床表现及辅助检查结果之间的相关性；第三部分采用免疫组织化学的方法检测新发病并未经治疗的成年PM/DM患者肌肉标本10例(PM6例,DM4例)及5例健康对照肌肉组织NALP1、NALP3、ASC及caspase-1的表达情况。
结果：第一部分：共收集1387例患者,其中PM者460(33.2%)例和DM者927(66.8%)例,女性980例,男性407例(女：男=2.4：1)。发病年龄为46.7±14.2(18-83)岁。74.3%(1031例)的患者出现至少1个器官损害,其中47.1%(486例)的患者出现2个及以上器官损害,11.9%(123例)的患者出现3个及以上器官损害,1.2%(12例)的患者出现4个器官损害。肺部损害(55.2%)发生率最高,其次是关节炎(32.3%)、心脏损害(27.5%)及消化道损害(21.9%)。多因素回归分析显示,肺部损害与年龄大于40岁正相关(OR3.135,95%CI2.145-4.582,P<0.01),与肌痛负相关(OR0.691,95%CI0.486-0.982,P<0.05)。与关节炎正相关的有发热(OR1.716,95%CI1.079-2.728,P 第三部分：4例DM患者肌肉组织中CD3+T细胞及CD20+B细胞均表达ASC及caspase-1,其中2例表达NALP3。6例PM患者中仅有1例肌肉组织中CD3+T细胞及CD20+B细胞表达NALP3、ASC及caspase-1。10例患者均不表达NALP1。5例正常对照肌肉组织均不表达NALP1、NALP3、ASC及caspase-1。DM组ASC及caspase-1的表达阳性率均(均为100%)高于PM组(均为16.7%)及正常对照组(均为0),差异均具有统计学意义(P<0.01和P0.05和P>O.05)。
结论：本研究是我国关于成人PM/DM最大规模的多中心回顾性研究,结果可以代表中国人群成人PM/DM的临床表现及器官损害的特点。成人PM/DM器官损害发生率高,年龄大于等于40岁,无肌痛的患者更易合并肺部损害；有雷诺现象和肌无力的患者更易合并消化道损害；有四肢肿胀的患者更易合并心脏损害；有体重下降的患者更可能有多个器官损害。C3M与PM/DM合并ILD存在显著相关性,是否可作为PM/DM合并ILD诊断的血清标志物仍需大样本随访研究进一步明确。在发病机制方面,固有免疫反应与调节在DM和PM中起不同的作用。炎症体可能参与DM的发病过程,部分由NALP3激活。而炎症体激活可能并不参与大部分PM的发病。
Objectives Adult polymyositis (PM) and dermatomyositis (DM) belong to the category of idiopathic inflammatory myopathy, which is a group of systemic autoimmune diseases characterized by the damage of skeletal muscles, skin and multiple organs. Organ involvement of PM/DM is the major factor affecting the prognosis of the diseases. The aims of this dissertation are:1) to organize the largest multi-center retrospective study of PM/DM in China, summarize and analyze the prevalence and characteristics of clinical features and main organ involvement in adult patients with PM and DM, and determine their specific relative factors;2) to investigate whether matrix metalloproteinases-9-cleaved fragment of type III collagen (C3M) may be used as novel markers for interstitial lung disease (ILD) in PM and DM;3) to discuss the possible pathogenesis of inflammasome in the diseases from the perspective of innate immune.
Methods This study is composed of three parts. In the first part of the study, we retrospectively collected the medical records of1387confirmed adult PM and DM patients accommodated from2007to2012in22rheumatology centers in China using unified questionnaire. Statistical analyses were done with chi-square or Fisher exact test and multivariate analyses with logistic regression method. In the second part, serum concentrations of C3M were determined by enzyme-linked immunosorbent assay in46adult PM/DM patients (31with ILD,15without ILD) and19healthy controls. The correlations between serum C3M levels and clinical features or laboratory examinations of PM/DM patients were investigated. In the third part, immunohistochemistry was performed to determine the expression of NALP (NACHT-LRR-PYD-containing protein), NALP3, ASC (apoptosis-associated speck-like protein containing a CARD) and caspase-1in muscle of10newly diagnosed and untreated adult DM/PM patients (6PM and4DM) and5healthy controls.
Results In the first part of the study, a total of1387patients were collected with460(33.2%) PM and927(66.8%) DM. There were980females and407males (female:male ratio of2.4:1). The onset age was46.7±14.2(18-82) years. A total of 1031(74.3%) patients had organ involvement. Among them,47.1%(486) patients had more than one organ involvement, while11.9%(123) had more than two,1.2%(12) had more than three. The prevalence of pulmonary involvement, arthritis, gastrointestinal and cardiac involvement were55.2%,32.3%,27.5%and21.9%, respectively. The multivariate analysis indicated that older onset age (OR3.135,95%CI2.145-4.582, P<0.01) was positively associated with pulmonary involvement, while myalgia (OR0.691,95%CI0.486-0.982, P<0.05) was negatively associated. Fever (OR1.716,95%CI1.079-2.728, P<0.05), weight loss (OR1.876,95%CI1.059-3.325, P<0.05) and Raynaud's phenomenon (OR3.523,95%CI1.794-6.920, P<0.01) were positively associated with arthritis, while muscle weakness (OR0.587,95%CI0.377-0.915, P<0.05) was negatively associated. Weight loss (OR1.916,95%CI1.019-3.600, P<0.05), Raynaud's phenomenon (OR3.331,95%CI1.509-7.356, P<0.01) and muscle weakness (OR2.056,95%CI1.029-4.108, P<0.05) were positively associated with gastrointestinal involvement. Weight loss (OR2.337,95%CI1.135-4.809, P<0.05) and swollen limbs (OR2.633,95%CI1.214-5.711, P<0.05) were positively associated with cardiac involvement. In the second part, the serum levels of C3M were7.16±3.77ng/ml in PM/DM with ILD group,4.56±0.84ng/ml in PM/DM without ILD group, and4.63±0.85ng/ml, in healthy controls, respectively. Serum C3M level in ILD group was significantly higher than without ILD group and healthy controls (both P<0.01). With cut-off value at5.42ng/ml, the sensitivity and specificity of positive C3M for ILD in PM/DM were71.0%and86.7%, respectively. The positive predictive value and negative predictive value of C3M were91.7%and59.1%, respectively. C3M was significantly related to PM/DM associated ILD. The serum levels of C3M were positively correlated with ESR and CRP levels, and negatively correlated with%DLCO.
In the third part, in muscle of4DM patients, ASC and caspase-1were expressed in the plasma of CD3+T and CD20+B cells, while in2of them NALP3was also expressed. Only1PM patient in6expressed NALP3, ASC and caspase-1in the plasma of CD3+T and CD20+B cells. NALP1was not expressed in all of the10patients. No NALP1, NALP3, ASC and caspase-1were expressed in the muscle of5healthy controls. The positive rate of ASC and caspase-1(both100%) in DM group was significantly higher than that in PM (both16.7%) and control group (both0)(P<0.01and P<0.05), while the positive rate of NALP3in DM group (50%) was higher than that in PM (16.7%) and control group (0), but with no statistical significance ((P>0.05and P>0.05).
Conclusions This is the largest multi-center retrospective study about adult PM/DM in China. The results can represent the characteristic of clinical features and organ involvement of PM/DM patients in Chinese population. The prevalence of organ involvement is high in adult patients with PM/DM. Patients with older onset age and no myalgia are more likely to have pulmonary involvement. Patients with Raynaud's phenomenon and muscle weakness are more likely to have gastrointestinal involvement. Patients with swollen limbs are more likely to have cardiac involvement. Patients with weight loss are more likely to have multiple organ involvement. C3M is significantly associated with ILD. Further study has to be done to confirm the diagnostic value for ILD in PM/DM patients. Innate immune plays different role in the pathogenesis of DM and PM. Inflammasome participates in the inflammation of DM but not in PM, and may be activated by NALP3.
对象和方法：本研究分为三部分：第一部分使用统一的调查表,回顾性收集所有于2007-2012年间在全国22个三级甲等医院风湿免疫科住院的符合纳入排除标准的1387例成人PM/DM患者的病例资料,并进行多因素logistic回归分析；第二部分采用酶联免疫吸附法检测46例成人PM/DM(30例合并ILD,15例不合并ILD)和19例正常对照血清C3M浓度,用ROC曲线分析C3M的诊断价值,并统计分析C3M与主要临床表现及辅助检查结果之间的相关性；第三部分采用免疫组织化学的方法检测新发病并未经治疗的成年PM/DM患者肌肉标本10例(PM6例,DM4例)及5例健康对照肌肉组织NALP1、NALP3、ASC及caspase-1的表达情况。
结果：第一部分：共收集1387例患者,其中PM者460(33.2%)例和DM者927(66.8%)例,女性980例,男性407例(女：男=2.4：1)。发病年龄为46.7±14.2(18-83)岁。74.3%(1031例)的患者出现至少1个器官损害,其中47.1%(486例)的患者出现2个及以上器官损害,11.9%(123例)的患者出现3个及以上器官损害,1.2%(12例)的患者出现4个器官损害。肺部损害(55.2%)发生率最高,其次是关节炎(32.3%)、心脏损害(27.5%)及消化道损害(21.9%)。多因素回归分析显示,肺部损害与年龄大于40岁正相关(OR3.135,95%CI2.145-4.582,P<0.01),与肌痛负相关(OR0.691,95%CI0.486-0.982,P<0.05)。与关节炎正相关的有发热(OR1.716,95%CI1.079-2.728,P
结论：本研究是我国关于成人PM/DM最大规模的多中心回顾性研究,结果可以代表中国人群成人PM/DM的临床表现及器官损害的特点。成人PM/DM器官损害发生率高,年龄大于等于40岁,无肌痛的患者更易合并肺部损害；有雷诺现象和肌无力的患者更易合并消化道损害；有四肢肿胀的患者更易合并心脏损害；有体重下降的患者更可能有多个器官损害。C3M与PM/DM合并ILD存在显著相关性,是否可作为PM/DM合并ILD诊断的血清标志物仍需大样本随访研究进一步明确。在发病机制方面,固有免疫反应与调节在DM和PM中起不同的作用。炎症体可能参与DM的发病过程,部分由NALP3激活。而炎症体激活可能并不参与大部分PM的发病。
Objectives Adult polymyositis (PM) and dermatomyositis (DM) belong to the category of idiopathic inflammatory myopathy, which is a group of systemic autoimmune diseases characterized by the damage of skeletal muscles, skin and multiple organs. Organ involvement of PM/DM is the major factor affecting the prognosis of the diseases. The aims of this dissertation are:1) to organize the largest multi-center retrospective study of PM/DM in China, summarize and analyze the prevalence and characteristics of clinical features and main organ involvement in adult patients with PM and DM, and determine their specific relative factors;2) to investigate whether matrix metalloproteinases-9-cleaved fragment of type III collagen (C3M) may be used as novel markers for interstitial lung disease (ILD) in PM and DM;3) to discuss the possible pathogenesis of inflammasome in the diseases from the perspective of innate immune.
Methods This study is composed of three parts. In the first part of the study, we retrospectively collected the medical records of1387confirmed adult PM and DM patients accommodated from2007to2012in22rheumatology centers in China using unified questionnaire. Statistical analyses were done with chi-square or Fisher exact test and multivariate analyses with logistic regression method. In the second part, serum concentrations of C3M were determined by enzyme-linked immunosorbent assay in46adult PM/DM patients (31with ILD,15without ILD) and19healthy controls. The correlations between serum C3M levels and clinical features or laboratory examinations of PM/DM patients were investigated. In the third part, immunohistochemistry was performed to determine the expression of NALP (NACHT-LRR-PYD-containing protein), NALP3, ASC (apoptosis-associated speck-like protein containing a CARD) and caspase-1in muscle of10newly diagnosed and untreated adult DM/PM patients (6PM and4DM) and5healthy controls.
Results In the first part of the study, a total of1387patients were collected with460(33.2%) PM and927(66.8%) DM. There were980females and407males (female:male ratio of2.4:1). The onset age was46.7±14.2(18-82) years. A total of 1031(74.3%) patients had organ involvement. Among them,47.1%(486) patients had more than one organ involvement, while11.9%(123) had more than two,1.2%(12) had more than three. The prevalence of pulmonary involvement, arthritis, gastrointestinal and cardiac involvement were55.2%,32.3%,27.5%and21.9%, respectively. The multivariate analysis indicated that older onset age (OR3.135,95%CI2.145-4.582, P<0.01) was positively associated with pulmonary involvement, while myalgia (OR0.691,95%CI0.486-0.982, P<0.05) was negatively associated. Fever (OR1.716,95%CI1.079-2.728, P<0.05), weight loss (OR1.876,95%CI1.059-3.325, P<0.05) and Raynaud's phenomenon (OR3.523,95%CI1.794-6.920, P<0.01) were positively associated with arthritis, while muscle weakness (OR0.587,95%CI0.377-0.915, P<0.05) was negatively associated. Weight loss (OR1.916,95%CI1.019-3.600, P<0.05), Raynaud's phenomenon (OR3.331,95%CI1.509-7.356, P<0.01) and muscle weakness (OR2.056,95%CI1.029-4.108, P<0.05) were positively associated with gastrointestinal involvement. Weight loss (OR2.337,95%CI1.135-4.809, P<0.05) and swollen limbs (OR2.633,95%CI1.214-5.711, P<0.05) were positively associated with cardiac involvement. In the second part, the serum levels of C3M were7.16±3.77ng/ml in PM/DM with ILD group,4.56±0.84ng/ml in PM/DM without ILD group, and4.63±0.85ng/ml, in healthy controls, respectively. Serum C3M level in ILD group was significantly higher than without ILD group and healthy controls (both P<0.01). With cut-off value at5.42ng/ml, the sensitivity and specificity of positive C3M for ILD in PM/DM were71.0%and86.7%, respectively. The positive predictive value and negative predictive value of C3M were91.7%and59.1%, respectively. C3M was significantly related to PM/DM associated ILD. The serum levels of C3M were positively correlated with ESR and CRP levels, and negatively correlated with%DLCO.
In the third part, in muscle of4DM patients, ASC and caspase-1were expressed in the plasma of CD3+T and CD20+B cells, while in2of them NALP3was also expressed. Only1PM patient in6expressed NALP3, ASC and caspase-1in the plasma of CD3+T and CD20+B cells. NALP1was not expressed in all of the10patients. No NALP1, NALP3, ASC and caspase-1were expressed in the muscle of5healthy controls. The positive rate of ASC and caspase-1(both100%) in DM group was significantly higher than that in PM (both16.7%) and control group (both0)(P<0.01and P<0.05), while the positive rate of NALP3in DM group (50%) was higher than that in PM (16.7%) and control group (0), but with no statistical significance ((P>0.05and P>0.05).
Conclusions This is the largest multi-center retrospective study about adult PM/DM in China. The results can represent the characteristic of clinical features and organ involvement of PM/DM patients in Chinese population. The prevalence of organ involvement is high in adult patients with PM/DM. Patients with older onset age and no myalgia are more likely to have pulmonary involvement. Patients with Raynaud's phenomenon and muscle weakness are more likely to have gastrointestinal involvement. Patients with swollen limbs are more likely to have cardiac involvement. Patients with weight loss are more likely to have multiple organ involvement. C3M is significantly associated with ILD. Further study has to be done to confirm the diagnostic value for ILD in PM/DM patients. Innate immune plays different role in the pathogenesis of DM and PM. Inflammasome participates in the inflammation of DM but not in PM, and may be activated by NALP3.
引文
[1]Selva-O'Callaghan A, Labrador-Horrillo M, Munoz-Gall X, et al. Polymyositis/dermatomyositis-associated lung disease:analysis of a series of 81 patients [J]. Lupus,2005,14(7):534-542.
[2]Hochberg MC, Feldman D, Stevens MB. Adult onset polymyositis/dermatomyositis:an analysis of clinical and laboratory features and survival in 76 patients with a review of the literature [J]. Semin Arthritis Rheum,1986,15(3):168-178.
[3]Limaye VS, Lester S, Blumbergs P, et al. Idiopathic inflammatory myositis is associated with a high incidence of hypertension and diabetes mellitus [J]. Int J Rheum Dis,2010,13(2):132-137.
[4]Strongwater SL, Annesley T, Schnitzer TJ. Myocardial involvement in polymyositis [J]. J Rheumatol,1983,10(3):459-463.
[5]Shinjo SK, Levy-Neto M. Anti-Jo-1 antisynthetase syndrome [J]. Rev Bras Reumatol,2010,50(5): 492-500.
[6]Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts) [J]. N Engl J Med,1975, 292(7):344-347.
[7]舒晓明,马丽,卢听,等.肌炎活动性评估工具应用于中国多发性肌炎/皮肌炎患者中的研究[J].中日友好医院学报,2011,25(2)：80-83.
[8]Ruperto N, Ravelli A, Pistorio A, et al. The provisional Paediatric Rheumatology International Trials Organisation/American College of Rheumatology/European League Against Rheumatism Disease activity core set for the evaluation of response to therapy in juvenile dermatomyositis:a prospective validation study [J]. Arthritis Rheum,2008,59(1):4-13.
[9]Torres C, Belmonte R, Carmona L, et al. Survival, mortality and causes of death in inflammatory myopathies [J]. Autoimmunity,2006,39(3):205-215.
[10]Ji SY, Zeng FQ, Guo Q, et al. Predictive factors and unfavourable prognostic factors of interstitial lung disease in patients with polymyositis or dermatomyositis:a retrospective study [J]. Chin Med J (Engl),2010,123(5):517-522.
[11]Marie I, Hatron PY, Levesque H, et al. Influence of age on characteristics of polymyositis and dermatomyositis in adults [J]. Medicine (Baltimore),1999,78(3):139-147.
[12]Friedman AW, Targoff IN, Arnett FC. Interstitial lung disease with autoantibodies against aminoacyl-tRNA synthetases in the absence of clinically apparent myositis [J]. Semin Arthritis Rheum,1996,26(1):459-467.
[13]Danko K, Ponyi A, Constantin T, et al. Long-term survival of patients with idiopathic inflammatory myopathies according to clinical features:a longitudinal study of 162 cases [J]. Medicine (Baltimore),2004,83(1):35-42.
[14]Gottdiener JS, Sherber HS, Hawley RJ, et al. Cardiac manifestations in polymyositis [J]. Am J Cardiol,1978,41(7):1141-1149.
[15]Gonzalez-Lopez L, Gamez-Nava JI, Sanchez L, et al. Cardiac manifestations in dermato-polymyositis [J]. Clin Exp Rheumatol,1996,14(4):373-379.
[16]Zhang L, Wang GC, Ma L, et al. Cardiac involvement in adult polymyositis or dermatomyositis:a systematic review [J]. Clin Cardiol,2012,35(11):686-691.
[17]Eshraghi N, Farahmand M, Maerz LL, et al. Adult-onset dermatomyositis with severe gastrointestinal manifestations:case report and review of the literature [J]. Surgery,1998,123(3): 356-358.
[18]Boardman P, Nolan DJ. Case report:Small intestinal pseudo-obstruction:an unusual manifestation of polymyositis [J]. Clin Radiol,1998,53(9):706-707.
[1]Saketkoo LA, Ascherman DP, Cottin V, et al. Interstitial Lung Disease in Idiopathic Inflammatory Myopathy [J]. Curr Rheumatol Rev,2010,6(2):108-119.
[2]Kubo M, Ihn H, Yamane K, et al. Serum KL-6 in adult patients with polymyositis and dermatomyositis [J]. Rheumatology (Oxford),2000,39(6):632-636.
[3]Ishii H, Mukae H, Kadota J, et al. High serum concentrations of surfactant protein A in usual interstitial pneumonia compared with non-specific interstitial pneumonia [J]. Thorax,2003,58(1): 52-57.
[4]Ihn H, Asano Y, Kubo M, et al. Clinical significance of serum surfactant protein D (SP-D) in patients with polymyositis/dermatomyositis:correlation with interstitial lung disease [J]. Rheumatology (Oxford),2002,41(11):1268-1272.
[5]Pierce JA, Hocott JB. Studies on the collagen and elastin content of the human lung [J]. J Clin Invest,1960,39:8-14.
[6]Fitzpatrick M, Hospelhorn VD. Studies of human pulmonary connective tissue. Ⅱ. Amino acid composition of residues following collagenase digestion of lung connective tissues [J]. Am Rev Respir Dis,1965,92(5):792-800.
[7]Low FN. Extracellular components of the pulmonary alveolar wall [J]. Arch Intern Med,1971, 127(5):847-852.
[8]Bradley KH, McConnell SD, Crystal RG Lung collagen composition and synthesis. Characterization and changes with age [J]. J Biol Chem,1974,249(9):2674-2683.
[9]Bradley K, McConnell-Breul S, Crystal RG. Lung collagen heterogeneity [J]. Proc Natl Acad Sci U S A,1974,71(7):2828-2832.
[10]Crystal RG, Fulmer JD, Baum BJ, et al. Cells, collagen and idiopathic pulmonary fibrosis [J]. Lung,1978,155(3):199-224.
[II]Hance AJ, Crystal RG The connective tissue of lung [J]. Am Rev Respir Dis,1975,112(5): 657-711.
[12]Gelse K, Poschl E, Aigner T. Collagens--structure, function, and biosynthesis [J]. Adv Drug Deliv Rev,2003,55(12):1531-1546.
[13]Shoulders MD, Raines RT. Collagen structure and stability [J]. Annu Rev Biochem,2009,78: 929-958.
[14]Raghu G, Striker LJ, Hudson LD, et al. Extracellular matrix in normal and fibrotic human lungs [J]. Am Rev Respir Dis,1985,131(2):281-289.
[15]侯显明,润江.间质性肺病学[M].人民卫生出版社,北京,2003,6月(第1版):573-575.
[16]Madri JA, Furthmayr H. Collagen polymorphism in the lung. An immunochemical study of pulmonary fibrosis [J]. Hum Pathol,1980,11(4):353-366.
[17]Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry [J]. Circ Res,2003,92(8):827-839.
[18]Reponen P, Sahlberg C, Munaut C, et al. High expression of 92-kD type IV collagenase (gelatinase B) in the osteoclast lineage during mouse development [J]. J Cell Biol,1994,124(6): 1091-1102.
[19]Bigg HF, Rowan AD, Barker MD, et al. Activity of matrix metalloproteinase-9 against native collagen types I and III [J]. FEBS J,2007,274(5):1246-1255.
[20]Geiser T. Idiopathic pulmonary fibrosis--a disorder of alveolar wound repair [J]? Swiss Med Wkly, 2003,133(29-30):405-411.
[21]Hamman L, Rich AR. Fulminating Diffuse Interstitial Fibrosis of the Lungs [J]. Trans Am Clin Climatol Assoc,1935,51:154-163.
[22]Dancer RC, Wood AM, Thickett DR. Metalloproteinases in idiopathic pulmonary fibrosis [J]. Eur Respir J,2011,38(6):1461-1467.
[23]Henry MT, McMahon K, Mackarel AJ, et al. Matrix metalloproteinases and tissue inhibitor of metalloproteinase-1 in sarcoidosis and IPF [J]. Eur Respir J,2002,20(5):1220-1227.
[24]Suga M, Iyonaga K, Okamoto T, et al. Characteristic elevation of matrix metalloproteinase activity in idiopathic interstitial pneumonias [J]. Am J Respir Crit Care Med,2000,162(5): 1949-1956.
[25]杜秀芳,马慧,杨伟国,等.特发性肺纤维化患者血清基质金属蛋白酶-9水平及其临床意义[J].中国综合临床,2005,21(2)：111-112.
[26]Selman M, Ruiz V, Cabrera S, et al. TIMP-1,-2,-3, and -4 in idiopathic pulmonary fibrosis. A prevailing nondegradative lung microenvironment [J]? Am J Physiol Lung Cell Mol Physiol,2000, 279(3):L562-574.
[27]庄虹.血管紧张素转化酶及基质金属蛋白酶原-9基因多态性与特发性肺纤维化的相关性研究[J]. 临床肺科杂志,2013,18(12):2222-2224.
[28]Zhen EY, Brittain IJ, Laska DA, et al. Characterization of metalloprotease cleavage products of human articular cartilage [J]. Arthritis Rheum,2008,58(8):2420-2431.
[29]Barascuk N, Veidal S, Larsen L, et al. A novel assay for extracellular matrix remodeling associated with liver fibrosis:an enzyme-linked immunosorbent assay (ELISA) for a MMP-9 proteolytically revealed neo-epitope of type III collagen [J]. Clin Biochem,2010,43(10-11): 899-904.
[30]Veidal SS, Vassiliadis E, Barascuk N, et al. Matrix metalloproteinase-9-mediated type III collagen degradation as a novel serological biochemical marker for liver fibrogenesis [J]. Liver Int,2010, 30(9):1293-1304.
[31]Vassiliadis E, Veidal SS, Barascuk N, et al. Measurement of matrix metalloproteinase 9-mediated collagen type III degradation fragment as a marker of skin fibrosis [J]. BMC Dermatol,2011,11: 6-12.
[32]Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts) [J]. N Engl J Med,1975, 292(7):344-347.
[33]Richards TJ EA, Gibson K, Yousem S, Fuhrman C, Gochuico BR, Fertig N, Oddis CV, Kaminski N, Rosas IO, Ascherman DP. Characterization and peripheral blood biomarker assessment of anti-Jo-1 antibody-positive interstitial lung disease [J]. Arthritis Rheum,2009,60(7):2183-2192.
[34]Isenberg DA, Allen E, Farewell V, et al. International consensus outcome measures for patients with idiopathic inflammatory myopathies. Development and initial validation of myositis activity and damage indices in patients with adult onset disease [J]. Rheumatology (Oxford),2004,43(1): 49-54.
[35]卢听,谢瑶,王国春.血清KL-6检测在特发性炎性肌病伴肺间质病变诊断中的价值[J].华风湿病学杂志,2006,10(7)：416-419.
[36]陈芳,舒晓明,王冬雪,等.血清肺表面活性蛋白-A,D检查在多发性肌炎/皮肌炎合并间质性肺病中的意义[J].中华医学杂志,2012,92(31)：2182-2185.
[37]陈芳,舒晓明,王冬雪,等.多发性肌炎及皮肌炎患者血清单核细胞趋化蛋白-1的测定及临床意义[J].北京大学学报(医学版),2012,44(2)：204-208.
[38]Mimori T, Imura Y, Nakashima R, et al. Autoantibodies in idiopathic inflammatory myopathy:an update on clinical and pathophysiological significance [J]. Curr Opin Rheumatol,2007,19(6): 523-529.
[39]Hirakata M. Autoantibodies to aminoacyl-tRNA synthetases [J]. Intern Med,2005,44(6): 527-528.
[1]Franchi L, McDonald C, Kanneganti TD, et al. Nucleotide-binding oligomerization domain-like receptors:intracellular pattern recognition molecules for pathogen detection and host defense [J]. J Immunol,2006,177(6):3507-3513.
[2]Petrilli V, Dostert C, Muruve DA, et al. The inflammasome:a danger sensing complex triggering innate immunity [J]. Curr Opin Immunol,2007,19(6):615-622.
[3]Yu HB, Finlay BB. The caspase-1 inflammasome:a pilot of innate immune responses [J]. Cell Host Microbe,2008,4(3):198-208.
[4]Mackiewicz Z, Hukkanen M, Povilenaite D, et al. Dual effects of caspase-1, interleukin-1 beta, tumour necrosis factor-alpha and nerve growth factor receptor in inflammatory myopathies [J]. Clin Exp Rheumatol,2003,21(1):41-48.
[5]Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts) [J]. N Engl J Med,1975, 292(7):344-347.
[6]Isenberg DA, Allen E, Farewell V, et al. International consensus outcome measures for patients with idiopathic inflammatory myopathies. Development and initial validation of myositis activity and damage indices in patients with adult onset disease [J]. Rheumatology (Oxford),2004,43(1): 49-54.
[7]卢昕,谢瑶,王国春,等.特发性炎性肌病骨骼肌炎症浸润的组织病理学分析[J].内科急危重症杂志,2008,14(3)：142-145.
[8]Hengstman GJ, van Engelen BG, Vree Egberts WT, et al. Myositis-specific autoantibodies: overview and recent developments [J]. Curr Opin Rheumatol,2001,13(6):476-482.
[9]Ting JP, Lovering RC, Alnemri ES, et al. The NLR gene family:a standard nomenclature [J]. Immunity,2008,28(3):285-287.
[10]Agostini L, Martinon F, Burns K, et al. NALP3 forms an IL-lbeta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder [J]. Immunity,2004,20(3): 319-325.
[11]Kolly L, Busso N, Palmer G, et al. Expression and function of the NALP3 inflammasome in rheumatoid synovium [J]. Immunology,2010,129(2):178-185.
[12]Magitta NF, Boe Wolff AS, Johansson S, et al. A coding polymorphism in NALP1 confers risk for autoimmune Addison's disease and type 1 diabetes [J]. Genes Immun,2009,10(2):120-124.
Petrilli V, Dostert C, Muruve DA, et al. The inflammasome:a danger sensing complex triggering innate immunity [J]. Curr Opin Immunol,2007,19(6):615-622.
Jin C, Flavell RA. Molecular mechanism of NLRP3 inflammasome activation [J]. J Clin Immunol,2010, 30(5):628-631.
Yu HB, Finlay BB. The caspase-1 inflammasome:a pilot of innate immune responses [J]. Cell Host Microbe,2008,4(3):198-208.
Marina-Garcia N, Franchi L, Kim YG, et al. Pannexin-1-mediated intracellular delivery of muramyl dipeptide induces caspase-1 activation via cryopyrin/NLRP3 independently of Nod2 [J]. J Immunol, 2008,180(6):4050-4057.
Lamkanfi M, Mueller JL, Vitari AC, et al. Glyburide inhibits the Cryopyrin/Nalp3 inflammasome [J]. J Cell Biol,2009,187(1):61-70.
Martinon F, Mayor A, Tschopp J. The inflammasomes:guardians of the body [J]. Annu Rev Immunol, 2009,27:229-265.
Halle A, Hornung V, Petzold GC, et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta [J]. Nat Immunol,2008,9(8):857-865.
Chae JJ, Komarow HD, Cheng J, et al. Targeted disruption of pyrin, the FMF protein, causes heightened sensitivity to endotoxin and a defect in macrophage apoptosis [J]. Mol Cell,2003,11(3):591-604.
Chae JJ, Wood G, Masters SL, et al. The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-lbeta production [J]. Proc Natl Acad Sci U S A, 2006,103(26):9982-9987.
Yu JW, Wu J, Zhang Z, et al. Cryopyrin and pyrin activate caspase-1, but not NF-kappaB, via ASC oligomerization [J]. Cell Death Differ,2006,13(2):236-249.
Papin S, Cuenin S, Agostini L, et al. The SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-lbeta processing [J]. Cell Death Differ,2007,14(8):1457-1466.
Hoffman HM, Mueller JL, Broide DH, et al. Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome [J]. Nat Genet, 2001,29(3):301-305.
Agostini L, Martinon F, Burns K, et al. NALP3 forms an IL-lbeta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder [J]. Immunity,2004,20(3):319-325.
Hawkins PN, Lachmann HJ, McDermott MF. Interleukin-1-receptor antagonist in the Muckle-Wells syndrome [J]. N Engl J Med,2003,348(25):2583-2584.
Hoffman HM, Rosengren S, Boyle DL, et al. Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist [J]. Lancet,2004, 364(9447):1779-1785.
Martinon F, Petrilli V, Mayor A, et al. Gout-associated uric acid crystals activate the NALP3 inflammasome [J]. Nature,2006,440(7081):237-241.
Chen CJ, Shi Y, Hearn A, et al. MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals [J]. J Clin Invest,2006,116(8):2262-2271.
So A, De Smedt T, Revaz S, et al. A pilot study of IL-1 inhibition by anakinra in acute gout [J]. Arthritis Res Ther,2007,9(2):R28.
Pascual V, Allantaz F, Arce E, et al. Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade [J]. J Exp Med,2005,201(9): 1479-1486.
Fitzgerald AA, Leclercq SA, Yan A, et al. Rapid responses to anakinra in patients with refractory adult-onset Still's disease [J]. Arthritis Rheum,2005,52(6):1794-1803.
Dinarello CA. Blocking IL-1 in systemic inflammation [J]. J Exp Med,2005,201(9):1355-1359.
Kastbom A, Verma D, Eriksson P, et al. Genetic variation in proteins of the cryopyrin inflammasome influences susceptibility and severity of rheumatoid arthritis (the Swedish TIRA project) [J]. Rheumatology (Oxford),2008,47(4):415-417.
Kastbom A, Johansson M, Verma D, et al. CARD8 p.C10X polymorphism is associated with inflammatory activity in early rheumatoid arthritis [J]. Ann Rheum Dis,2010,69(4):723-726. Kolly L, Busso N, Palmer G, et al. Expression and function of the NALP3 inflammasome in rheumatoid synovium [J]. Immunology,2010,129(2):178-185.
Liu-Bryan R. Intracellular innate immunity in gouty arthritis:role of NALP3 inflammasome [J]. Immunol Cell Biol,2010,88(1):20-23.
Ippagunta SK, Brand DD, Luo J, et al. Inflammasome-independent role of apoptosis-associated speck-like protein containing a CARD (ASC) in T cell priming is critical for collagen-induced arthritis [J]. J Biol Chem,2010,285(16):12454-12462.
Kolly L, Karababa M, Joosten LA, et al. Inflammatory role of ASC in antigen-induced arthritis is independent of caspase-1, NALP-3, and IPAF [J]. J Immunol,2009,183(6):4003-4012.
Kimkong I, Avihingsanon Y, Hirankarn N. Expression profile of HIN200 in leukocytes and renal biopsy of SLE patients by real-time RT-PCR [J]. Lupus,2009,18(12):1066-1072.
Ostendorf B, Iking-Konert C, Kurz K, et al. Preliminary results of safety and efficacy of the interleukin 1 receptor antagonist anakinra in patients with severe lupus arthritis. [J] Ann Rheum Dis,2005,64(4): 630-633.
[30]Calvani N, Tucci M, Richards HB, et al. Thl cytokines in the pathogenesis of lupus nephritis:the role of IL-18 [J]. Autoimmun Rev,2005,4(8):542-548.
[31]Glinsky GV. SNP-guided microRNA maps (MirMaps) of 16 common human disorders identify a clinically accessible therapy reversing transcriptional aberrations of nuclear import and inflammasome pathways [J]. Cell Cycle,2008,7(22):3564-3576.
[32]Magitta NF, Boe Wolff AS, Johansson S, et al. A coding polymorphism in NALP1 confers risk for autoimmune Addison's disease and type 1 diabetes [J]. Genes Immun,2009,10(2):120-124.
[33]Pontillo A, Brandao L, Guimaraes R, et al. Two SNPs in NLRP3 gene are involved in the predisposition to type-1 diabetes and celiac disease in a pediatric population from northeast Brazil [J]. Autoimmunity, 2010,43(8):583-589.
[34]Hitomi Y, Ebisawa M, Tomikawa M, et al. Associations of functional NLRP3 polymorphisms with susceptibility to food-induced anaphylaxis and aspirin-induced asthma [J]. J Allergy Clin Immunol, 2009,124(4):779-785 e776.
[35]Schott WH, Haskell BD, Tse HM, et al. Caspase-1 is not required for type 1 diabetes in the NOD mouse [J]. Diabetes,2004,53(1):99-104.
[36]Vincent JA, Mohr S. Inhibition of caspase-1/interleukin-lbeta signaling prevents degeneration of retinal capillaries in diabetes and galactosemia. Diabetes [J],2007,56(1):224-230.
[2]Hochberg MC, Feldman D, Stevens MB. Adult onset polymyositis/dermatomyositis:an analysis of clinical and laboratory features and survival in 76 patients with a review of the literature [J]. Semin Arthritis Rheum,1986,15(3):168-178.
[3]Limaye VS, Lester S, Blumbergs P, et al. Idiopathic inflammatory myositis is associated with a high incidence of hypertension and diabetes mellitus [J]. Int J Rheum Dis,2010,13(2):132-137.
[4]Strongwater SL, Annesley T, Schnitzer TJ. Myocardial involvement in polymyositis [J]. J Rheumatol,1983,10(3):459-463.
[5]Shinjo SK, Levy-Neto M. Anti-Jo-1 antisynthetase syndrome [J]. Rev Bras Reumatol,2010,50(5): 492-500.
[6]Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts) [J]. N Engl J Med,1975, 292(7):344-347.
[7]舒晓明,马丽,卢听,等.肌炎活动性评估工具应用于中国多发性肌炎/皮肌炎患者中的研究[J].中日友好医院学报,2011,25(2)：80-83.
[8]Ruperto N, Ravelli A, Pistorio A, et al. The provisional Paediatric Rheumatology International Trials Organisation/American College of Rheumatology/European League Against Rheumatism Disease activity core set for the evaluation of response to therapy in juvenile dermatomyositis:a prospective validation study [J]. Arthritis Rheum,2008,59(1):4-13.
[9]Torres C, Belmonte R, Carmona L, et al. Survival, mortality and causes of death in inflammatory myopathies [J]. Autoimmunity,2006,39(3):205-215.
[10]Ji SY, Zeng FQ, Guo Q, et al. Predictive factors and unfavourable prognostic factors of interstitial lung disease in patients with polymyositis or dermatomyositis:a retrospective study [J]. Chin Med J (Engl),2010,123(5):517-522.
[11]Marie I, Hatron PY, Levesque H, et al. Influence of age on characteristics of polymyositis and dermatomyositis in adults [J]. Medicine (Baltimore),1999,78(3):139-147.
[12]Friedman AW, Targoff IN, Arnett FC. Interstitial lung disease with autoantibodies against aminoacyl-tRNA synthetases in the absence of clinically apparent myositis [J]. Semin Arthritis Rheum,1996,26(1):459-467.
[13]Danko K, Ponyi A, Constantin T, et al. Long-term survival of patients with idiopathic inflammatory myopathies according to clinical features:a longitudinal study of 162 cases [J]. Medicine (Baltimore),2004,83(1):35-42.
[14]Gottdiener JS, Sherber HS, Hawley RJ, et al. Cardiac manifestations in polymyositis [J]. Am J Cardiol,1978,41(7):1141-1149.
[15]Gonzalez-Lopez L, Gamez-Nava JI, Sanchez L, et al. Cardiac manifestations in dermato-polymyositis [J]. Clin Exp Rheumatol,1996,14(4):373-379.
[16]Zhang L, Wang GC, Ma L, et al. Cardiac involvement in adult polymyositis or dermatomyositis:a systematic review [J]. Clin Cardiol,2012,35(11):686-691.
[17]Eshraghi N, Farahmand M, Maerz LL, et al. Adult-onset dermatomyositis with severe gastrointestinal manifestations:case report and review of the literature [J]. Surgery,1998,123(3): 356-358.
[18]Boardman P, Nolan DJ. Case report:Small intestinal pseudo-obstruction:an unusual manifestation of polymyositis [J]. Clin Radiol,1998,53(9):706-707.
[1]Saketkoo LA, Ascherman DP, Cottin V, et al. Interstitial Lung Disease in Idiopathic Inflammatory Myopathy [J]. Curr Rheumatol Rev,2010,6(2):108-119.
[2]Kubo M, Ihn H, Yamane K, et al. Serum KL-6 in adult patients with polymyositis and dermatomyositis [J]. Rheumatology (Oxford),2000,39(6):632-636.
[3]Ishii H, Mukae H, Kadota J, et al. High serum concentrations of surfactant protein A in usual interstitial pneumonia compared with non-specific interstitial pneumonia [J]. Thorax,2003,58(1): 52-57.
[4]Ihn H, Asano Y, Kubo M, et al. Clinical significance of serum surfactant protein D (SP-D) in patients with polymyositis/dermatomyositis:correlation with interstitial lung disease [J]. Rheumatology (Oxford),2002,41(11):1268-1272.
[5]Pierce JA, Hocott JB. Studies on the collagen and elastin content of the human lung [J]. J Clin Invest,1960,39:8-14.
[6]Fitzpatrick M, Hospelhorn VD. Studies of human pulmonary connective tissue. Ⅱ. Amino acid composition of residues following collagenase digestion of lung connective tissues [J]. Am Rev Respir Dis,1965,92(5):792-800.
[7]Low FN. Extracellular components of the pulmonary alveolar wall [J]. Arch Intern Med,1971, 127(5):847-852.
[8]Bradley KH, McConnell SD, Crystal RG Lung collagen composition and synthesis. Characterization and changes with age [J]. J Biol Chem,1974,249(9):2674-2683.
[9]Bradley K, McConnell-Breul S, Crystal RG. Lung collagen heterogeneity [J]. Proc Natl Acad Sci U S A,1974,71(7):2828-2832.
[10]Crystal RG, Fulmer JD, Baum BJ, et al. Cells, collagen and idiopathic pulmonary fibrosis [J]. Lung,1978,155(3):199-224.
[II]Hance AJ, Crystal RG The connective tissue of lung [J]. Am Rev Respir Dis,1975,112(5): 657-711.
[12]Gelse K, Poschl E, Aigner T. Collagens--structure, function, and biosynthesis [J]. Adv Drug Deliv Rev,2003,55(12):1531-1546.
[13]Shoulders MD, Raines RT. Collagen structure and stability [J]. Annu Rev Biochem,2009,78: 929-958.
[14]Raghu G, Striker LJ, Hudson LD, et al. Extracellular matrix in normal and fibrotic human lungs [J]. Am Rev Respir Dis,1985,131(2):281-289.
[15]侯显明,润江.间质性肺病学[M].人民卫生出版社,北京,2003,6月(第1版):573-575.
[16]Madri JA, Furthmayr H. Collagen polymorphism in the lung. An immunochemical study of pulmonary fibrosis [J]. Hum Pathol,1980,11(4):353-366.
[17]Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry [J]. Circ Res,2003,92(8):827-839.
[18]Reponen P, Sahlberg C, Munaut C, et al. High expression of 92-kD type IV collagenase (gelatinase B) in the osteoclast lineage during mouse development [J]. J Cell Biol,1994,124(6): 1091-1102.
[19]Bigg HF, Rowan AD, Barker MD, et al. Activity of matrix metalloproteinase-9 against native collagen types I and III [J]. FEBS J,2007,274(5):1246-1255.
[20]Geiser T. Idiopathic pulmonary fibrosis--a disorder of alveolar wound repair [J]? Swiss Med Wkly, 2003,133(29-30):405-411.
[21]Hamman L, Rich AR. Fulminating Diffuse Interstitial Fibrosis of the Lungs [J]. Trans Am Clin Climatol Assoc,1935,51:154-163.
[22]Dancer RC, Wood AM, Thickett DR. Metalloproteinases in idiopathic pulmonary fibrosis [J]. Eur Respir J,2011,38(6):1461-1467.
[23]Henry MT, McMahon K, Mackarel AJ, et al. Matrix metalloproteinases and tissue inhibitor of metalloproteinase-1 in sarcoidosis and IPF [J]. Eur Respir J,2002,20(5):1220-1227.
[24]Suga M, Iyonaga K, Okamoto T, et al. Characteristic elevation of matrix metalloproteinase activity in idiopathic interstitial pneumonias [J]. Am J Respir Crit Care Med,2000,162(5): 1949-1956.
[25]杜秀芳,马慧,杨伟国,等.特发性肺纤维化患者血清基质金属蛋白酶-9水平及其临床意义[J].中国综合临床,2005,21(2)：111-112.
[26]Selman M, Ruiz V, Cabrera S, et al. TIMP-1,-2,-3, and -4 in idiopathic pulmonary fibrosis. A prevailing nondegradative lung microenvironment [J]? Am J Physiol Lung Cell Mol Physiol,2000, 279(3):L562-574.
[27]庄虹.血管紧张素转化酶及基质金属蛋白酶原-9基因多态性与特发性肺纤维化的相关性研究[J]. 临床肺科杂志,2013,18(12):2222-2224.
[28]Zhen EY, Brittain IJ, Laska DA, et al. Characterization of metalloprotease cleavage products of human articular cartilage [J]. Arthritis Rheum,2008,58(8):2420-2431.
[29]Barascuk N, Veidal S, Larsen L, et al. A novel assay for extracellular matrix remodeling associated with liver fibrosis:an enzyme-linked immunosorbent assay (ELISA) for a MMP-9 proteolytically revealed neo-epitope of type III collagen [J]. Clin Biochem,2010,43(10-11): 899-904.
[30]Veidal SS, Vassiliadis E, Barascuk N, et al. Matrix metalloproteinase-9-mediated type III collagen degradation as a novel serological biochemical marker for liver fibrogenesis [J]. Liver Int,2010, 30(9):1293-1304.
[31]Vassiliadis E, Veidal SS, Barascuk N, et al. Measurement of matrix metalloproteinase 9-mediated collagen type III degradation fragment as a marker of skin fibrosis [J]. BMC Dermatol,2011,11: 6-12.
[32]Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts) [J]. N Engl J Med,1975, 292(7):344-347.
[33]Richards TJ EA, Gibson K, Yousem S, Fuhrman C, Gochuico BR, Fertig N, Oddis CV, Kaminski N, Rosas IO, Ascherman DP. Characterization and peripheral blood biomarker assessment of anti-Jo-1 antibody-positive interstitial lung disease [J]. Arthritis Rheum,2009,60(7):2183-2192.
[34]Isenberg DA, Allen E, Farewell V, et al. International consensus outcome measures for patients with idiopathic inflammatory myopathies. Development and initial validation of myositis activity and damage indices in patients with adult onset disease [J]. Rheumatology (Oxford),2004,43(1): 49-54.
[35]卢听,谢瑶,王国春.血清KL-6检测在特发性炎性肌病伴肺间质病变诊断中的价值[J].华风湿病学杂志,2006,10(7)：416-419.
[36]陈芳,舒晓明,王冬雪,等.血清肺表面活性蛋白-A,D检查在多发性肌炎/皮肌炎合并间质性肺病中的意义[J].中华医学杂志,2012,92(31)：2182-2185.
[37]陈芳,舒晓明,王冬雪,等.多发性肌炎及皮肌炎患者血清单核细胞趋化蛋白-1的测定及临床意义[J].北京大学学报(医学版),2012,44(2)：204-208.
[38]Mimori T, Imura Y, Nakashima R, et al. Autoantibodies in idiopathic inflammatory myopathy:an update on clinical and pathophysiological significance [J]. Curr Opin Rheumatol,2007,19(6): 523-529.
[39]Hirakata M. Autoantibodies to aminoacyl-tRNA synthetases [J]. Intern Med,2005,44(6): 527-528.
[1]Franchi L, McDonald C, Kanneganti TD, et al. Nucleotide-binding oligomerization domain-like receptors:intracellular pattern recognition molecules for pathogen detection and host defense [J]. J Immunol,2006,177(6):3507-3513.
[2]Petrilli V, Dostert C, Muruve DA, et al. The inflammasome:a danger sensing complex triggering innate immunity [J]. Curr Opin Immunol,2007,19(6):615-622.
[3]Yu HB, Finlay BB. The caspase-1 inflammasome:a pilot of innate immune responses [J]. Cell Host Microbe,2008,4(3):198-208.
[4]Mackiewicz Z, Hukkanen M, Povilenaite D, et al. Dual effects of caspase-1, interleukin-1 beta, tumour necrosis factor-alpha and nerve growth factor receptor in inflammatory myopathies [J]. Clin Exp Rheumatol,2003,21(1):41-48.
[5]Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts) [J]. N Engl J Med,1975, 292(7):344-347.
[6]Isenberg DA, Allen E, Farewell V, et al. International consensus outcome measures for patients with idiopathic inflammatory myopathies. Development and initial validation of myositis activity and damage indices in patients with adult onset disease [J]. Rheumatology (Oxford),2004,43(1): 49-54.
[7]卢昕,谢瑶,王国春,等.特发性炎性肌病骨骼肌炎症浸润的组织病理学分析[J].内科急危重症杂志,2008,14(3)：142-145.
[8]Hengstman GJ, van Engelen BG, Vree Egberts WT, et al. Myositis-specific autoantibodies: overview and recent developments [J]. Curr Opin Rheumatol,2001,13(6):476-482.
[9]Ting JP, Lovering RC, Alnemri ES, et al. The NLR gene family:a standard nomenclature [J]. Immunity,2008,28(3):285-287.
[10]Agostini L, Martinon F, Burns K, et al. NALP3 forms an IL-lbeta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder [J]. Immunity,2004,20(3): 319-325.
[11]Kolly L, Busso N, Palmer G, et al. Expression and function of the NALP3 inflammasome in rheumatoid synovium [J]. Immunology,2010,129(2):178-185.
[12]Magitta NF, Boe Wolff AS, Johansson S, et al. A coding polymorphism in NALP1 confers risk for autoimmune Addison's disease and type 1 diabetes [J]. Genes Immun,2009,10(2):120-124.
Petrilli V, Dostert C, Muruve DA, et al. The inflammasome:a danger sensing complex triggering innate immunity [J]. Curr Opin Immunol,2007,19(6):615-622.
Jin C, Flavell RA. Molecular mechanism of NLRP3 inflammasome activation [J]. J Clin Immunol,2010, 30(5):628-631.
Yu HB, Finlay BB. The caspase-1 inflammasome:a pilot of innate immune responses [J]. Cell Host Microbe,2008,4(3):198-208.
Marina-Garcia N, Franchi L, Kim YG, et al. Pannexin-1-mediated intracellular delivery of muramyl dipeptide induces caspase-1 activation via cryopyrin/NLRP3 independently of Nod2 [J]. J Immunol, 2008,180(6):4050-4057.
Lamkanfi M, Mueller JL, Vitari AC, et al. Glyburide inhibits the Cryopyrin/Nalp3 inflammasome [J]. J Cell Biol,2009,187(1):61-70.
Martinon F, Mayor A, Tschopp J. The inflammasomes:guardians of the body [J]. Annu Rev Immunol, 2009,27:229-265.
Halle A, Hornung V, Petzold GC, et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta [J]. Nat Immunol,2008,9(8):857-865.
Chae JJ, Komarow HD, Cheng J, et al. Targeted disruption of pyrin, the FMF protein, causes heightened sensitivity to endotoxin and a defect in macrophage apoptosis [J]. Mol Cell,2003,11(3):591-604.
Chae JJ, Wood G, Masters SL, et al. The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-lbeta production [J]. Proc Natl Acad Sci U S A, 2006,103(26):9982-9987.
Yu JW, Wu J, Zhang Z, et al. Cryopyrin and pyrin activate caspase-1, but not NF-kappaB, via ASC oligomerization [J]. Cell Death Differ,2006,13(2):236-249.
Papin S, Cuenin S, Agostini L, et al. The SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-lbeta processing [J]. Cell Death Differ,2007,14(8):1457-1466.
Hoffman HM, Mueller JL, Broide DH, et al. Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome [J]. Nat Genet, 2001,29(3):301-305.
Agostini L, Martinon F, Burns K, et al. NALP3 forms an IL-lbeta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder [J]. Immunity,2004,20(3):319-325.
Hawkins PN, Lachmann HJ, McDermott MF. Interleukin-1-receptor antagonist in the Muckle-Wells syndrome [J]. N Engl J Med,2003,348(25):2583-2584.
Hoffman HM, Rosengren S, Boyle DL, et al. Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist [J]. Lancet,2004, 364(9447):1779-1785.
Martinon F, Petrilli V, Mayor A, et al. Gout-associated uric acid crystals activate the NALP3 inflammasome [J]. Nature,2006,440(7081):237-241.
Chen CJ, Shi Y, Hearn A, et al. MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals [J]. J Clin Invest,2006,116(8):2262-2271.
So A, De Smedt T, Revaz S, et al. A pilot study of IL-1 inhibition by anakinra in acute gout [J]. Arthritis Res Ther,2007,9(2):R28.
Pascual V, Allantaz F, Arce E, et al. Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade [J]. J Exp Med,2005,201(9): 1479-1486.
Fitzgerald AA, Leclercq SA, Yan A, et al. Rapid responses to anakinra in patients with refractory adult-onset Still's disease [J]. Arthritis Rheum,2005,52(6):1794-1803.
Dinarello CA. Blocking IL-1 in systemic inflammation [J]. J Exp Med,2005,201(9):1355-1359.
Kastbom A, Verma D, Eriksson P, et al. Genetic variation in proteins of the cryopyrin inflammasome influences susceptibility and severity of rheumatoid arthritis (the Swedish TIRA project) [J]. Rheumatology (Oxford),2008,47(4):415-417.
Kastbom A, Johansson M, Verma D, et al. CARD8 p.C10X polymorphism is associated with inflammatory activity in early rheumatoid arthritis [J]. Ann Rheum Dis,2010,69(4):723-726. Kolly L, Busso N, Palmer G, et al. Expression and function of the NALP3 inflammasome in rheumatoid synovium [J]. Immunology,2010,129(2):178-185.
Liu-Bryan R. Intracellular innate immunity in gouty arthritis:role of NALP3 inflammasome [J]. Immunol Cell Biol,2010,88(1):20-23.
Ippagunta SK, Brand DD, Luo J, et al. Inflammasome-independent role of apoptosis-associated speck-like protein containing a CARD (ASC) in T cell priming is critical for collagen-induced arthritis [J]. J Biol Chem,2010,285(16):12454-12462.
Kolly L, Karababa M, Joosten LA, et al. Inflammatory role of ASC in antigen-induced arthritis is independent of caspase-1, NALP-3, and IPAF [J]. J Immunol,2009,183(6):4003-4012.
Kimkong I, Avihingsanon Y, Hirankarn N. Expression profile of HIN200 in leukocytes and renal biopsy of SLE patients by real-time RT-PCR [J]. Lupus,2009,18(12):1066-1072.
Ostendorf B, Iking-Konert C, Kurz K, et al. Preliminary results of safety and efficacy of the interleukin 1 receptor antagonist anakinra in patients with severe lupus arthritis. [J] Ann Rheum Dis,2005,64(4): 630-633.
[30]Calvani N, Tucci M, Richards HB, et al. Thl cytokines in the pathogenesis of lupus nephritis:the role of IL-18 [J]. Autoimmun Rev,2005,4(8):542-548.
[31]Glinsky GV. SNP-guided microRNA maps (MirMaps) of 16 common human disorders identify a clinically accessible therapy reversing transcriptional aberrations of nuclear import and inflammasome pathways [J]. Cell Cycle,2008,7(22):3564-3576.
[32]Magitta NF, Boe Wolff AS, Johansson S, et al. A coding polymorphism in NALP1 confers risk for autoimmune Addison's disease and type 1 diabetes [J]. Genes Immun,2009,10(2):120-124.
[33]Pontillo A, Brandao L, Guimaraes R, et al. Two SNPs in NLRP3 gene are involved in the predisposition to type-1 diabetes and celiac disease in a pediatric population from northeast Brazil [J]. Autoimmunity, 2010,43(8):583-589.
[34]Hitomi Y, Ebisawa M, Tomikawa M, et al. Associations of functional NLRP3 polymorphisms with susceptibility to food-induced anaphylaxis and aspirin-induced asthma [J]. J Allergy Clin Immunol, 2009,124(4):779-785 e776.
[35]Schott WH, Haskell BD, Tse HM, et al. Caspase-1 is not required for type 1 diabetes in the NOD mouse [J]. Diabetes,2004,53(1):99-104.
[36]Vincent JA, Mohr S. Inhibition of caspase-1/interleukin-lbeta signaling prevents degeneration of retinal capillaries in diabetes and galactosemia. Diabetes [J],2007,56(1):224-230.