| Polymyositis and dermatomyositis (PM/DM) are systemic autoimmune diseases of unknown etiology that mainly affect skeletal muscles and other internal organs. ILD is an increasingly recognized condition associated with PM and DM; the presence of ILD affects the prognosis and requires a more aggressive approach in therapy. Therefore, it will be of great importance to find predictive factors and serum markers for ILD in PM/DM patients to assess the risk of ILD, diagnosis in early stage and to provide guidance for timely threrapy and progonosis evaluation. Previous studies have suggested many predictive factors for ILD in PM/DM patients. Nevertheless, their conclusions differed due to small sample size and dispersed study factors. In recent years, some studies have focused on the serum markers on ILD in PM/DM patients, however, the study target were often single and systematically follow-up studies were lacked. Anti-MDA5antibody was originally reported to closely relate with clinical amyopathic dermatomyositis (CADM) and A/SIP by Japanese researchers, however, the reports of anti-MDA5in other countries are rare.Objective1. To systematically review and evaluate the predictive factors of interstitial lung disease in the patients with polymyositis and dermatomyositis (PM/DM), and provide evidence for early clinical2. To detect and compare the diagnostic value of serum biomarkers for ILD in PM/DM patients and their association with clinical features.3. To evaluate and compare the predictive value of serum biomarkers for early diagnosis, monitoring disease course and predicting prognosis of ILD in patients with PM/DM.4. To determine serum anti-melanoma differenciation-associated gene5prevalence and their clinical associations in Chinese patients with polymyositis and dermatomyositis (PM/DM).Methods:1. The predictive factors of PM/DM-related ILD from23published papers were analyzed by Meta-analysis method. Analysis of heterogeneity and sensitivity were performed and pooled odds ratio(OR) with95%confidence interval were calculated using either fixed or random effects models by RevMan4.2software. Stata software was used to identify publication bias.2. Serum levels of KL-6, monocyte chemotactic protein-1(MCP-1), Surfactant protein-A,D(SP-A,SP-D) and anti-ARS antibody were detected by EL1SA in100adult PM/DM patients,20patients with pulmonary infection and42healthy controls. Various follow-ups were made to evaluate the predictive values of serum markers for diagnosing ILD, monitoring the course of ILD and the prognosis of ILD in patients with IIM.3. Serum anti-MDA5antibody were detected by ELISA in119adult PM/DM patients,30patients with SLE,30patients with RA,15patients with SS,21patients with pulmonary infection and50healthy controls. The association with clinical features and serum anti-MDA5antibody was analyzed.Results1. Meta-analysis was performed to analyze seven factors including anti-Jo-1antibody, fever, arthritis/arthralgia, Gottron’s sign, antinuclear antibody, Raynaud’s phenomenon and dysphagia. Factors correlated with interstitial lung disease in the patients with PM/DM and their OR values and95%CI were as follows:the presence of anti-Jo-1antibody6.94(4.74～10.16), fever4.90(3.82～6.29), arthritis/arthralgia3.93(3.21-4.80), Gottron’s sign2.52(1.24～5.14), and the presence of antinuclear antibody (ANA)1.59(1.02～2.47). Raynaud’s phenomenon and dysphagia are not correlated with interstitial lung disease in the patients with PM/DM with OR values and95%CI as1.40(0.97～2.01), and1.21(0.94～1.56) respectively.2. serum KL-6, MCP-1, SP-A,SP-D,anti-ARS antibody were significantly elevated in IIM patients with ILD(all P<0.05). KL-6showed the highest value (sensitivity80.6%and specificity90.9%) for diagnosing ILD. Anti-ARS antibody presented a significantly higher sensitivity for diagnosing ILD in patients with PM/DM compared with anti-Jo-1antibody (P<0.001).3.17PM/DM patients without ILD with high level of one or more markers were followed up for one year and the predictive value for each markers were as follows: SP-A20%(1/5),SP-D16%(1/6),MCP-122%(2/9),KL-657%(4/7).13ILD patients with PM/DM were treated and followed-up for2-6months, the serum levels of SP-A,SP-D,MCP-l,KL-6were raised or decreased with the improvement or worsening of ILD. SP-A(OR1.032,95%CI1.006～1.059, P=0.02) and KL-6(OR4.7, 95%CI3.34～5.82, P=0.009) were independent risk factor for death of1LD in PM/DM patients.4. Serum anti-MDA5antibody positive rate in the DM patients (22.6%) were significantly higher compared with PM patients(0%,P<0.005), patients with SLE(3.3%,P<0.05), RA(3.3%,P<0.05), SS(0%,P<0.05) and pulmonary infection(0%,P<0.05) and healthy controls(0%,P<0.001). In DM subgroup, CADM patients presented a higher positive anti-MDA5antibody rate than classic DM patients. The rate of acute/subacute interstitial pneumonia (A/SIP) was significantly higher in anti-MDA5positive DM patients than anti-MDA5negative DM patients. The sensitivity and specificity of anti-MDA5antibody for diagnosing A/SIP in DM patients were88.2%and94%respectively.14A/SIP patients with positive anti-MDA5were treated and followed up for2-6months,5patients got improved and turned into CIP, their serum anti-MDA5disappeaed. Additionally, logistic multivariate analysis showed anti-MDA5is an independent risk factor for death of ILD in DM(OR=8.46,95%CI1.77-40.36, P=0.007).Conclusions1. The presence of anti-Jo-1antibody, fever, arthritis/arthralgia, Gottron’s sign and ANA are major predictive factors of interstitial lung disease in the patients with PM/DM.2.Serum KL-6, MCP-1, SP-A,SP-D and anti-ARS are useful markers for ILD in PM/DM patients, of which KL-6presented highest diagnosing and predictive value. These biomarkers can help diagnosing ILD and monitoring the course of ILD. They can also predicting prognosis in IIM patients with ILD though they cannot replace conventional diagnosing procedure.3. In Chinese PM/DM patients, Serum antiMDA5antibody is mainly presented in DM patients. It is a strong predictor for diagnosing of DM with A/SIP and can disappear when A/SIP gets improved. It is an independent risk factor for death of ILD in DM. |
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