| 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. |
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