Qinglin Peng

Factors Predicting Malignancy in Patients with Polymyositis and Dermatomyostis: A Systematic Review and Meta-Analysis

Objective To define potential factors that could predict concomitant neoplastic diseases in patients diagnosed with PM/DM, which could inform screening decisions. Methods Two researchers independently reviewed articles from Pubmed (MEDLINE), EMBASE, Cochrane Plus Library and ISI Web of Knowledge with no restrictions on study design or language. Given that some of the studies combined PM and DM patients as research subjects while others included only DM patients, data were subjected to meta-analyses for all combined PM/DM studies and studies that included only DM patients to obtain informative results. Results For PM/DM patients, the following factors are all associated with an increased risk of malignancy: older age, age greater than 45, male sex, dysphagia, cutaneous necrosis, cutaneous vasculitis, rapid onset of myostis (<4 weeks), elevated CK, higher ESR, higher CRP levels. Several factors were associated with lower-than-average risk, including the presence of ILD, arthritis/arthralgia, Raynauds syndrome, or anti-Jo-1 antibody. For DM patients, results indicated an increased risk of malignancy with older age, male sex, the presence of cutaneous necrosis, elevated ESR (>35 mm/hr), higher CRP levels, or anti-p155 antibody. In addition, the presence of anti-ENA antibodies seem to be related to reduced risk of malignancy. Conclusion Awareness and implementation of early-stage cancer screening in PM/DM patients who have these identified factors – such as being older than 45, male sex, cutaneous necrosis, cutaneous vasculitis – are of crucial importance from public health and clinical perspectives and provide insight into the etiopathogenesis of CAM.

Clinical Characteristics of Anti-3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Antibodies in Chinese Patients with Idiopathic Inflammatory Myopathies.

Objective The objective of this study was to detect the prevalence of anti-3-hydroxyl-3- methylglutaryl coenzyme A reductase (anti-HMGCR) antibodies in Chinese patients with idiopathic inflammatory myopathies (IIMs), and to analyze the clinical features of the antibody-positive IIM patients. Methods The presence of anti-HMGCR antibodies was detected in 405 patients with IIMs, 90 healthy controls, and 221 patients with other rheumatic diseases by using an ELISA kit. Clinical data from anti-HMGCR antibody-positive and -negative patients were compared. Long-term follow-up of the anti-HMGCR antibody-positive patients was conducted to evaluate the role of anti-HMGCR antibody in IIM disease prognosis. Results Of the 405 IIM patients, 22 (5.4%) were found to carry the anti-HMGCR antibody. These IIM patients were predominantly female (73%), and only 3 anti-HMGCR antibody-positive patients with IIM were exposure to statins. Most patients experienced progressive onset, and presented with muscular weakness. Dysphagia was observed in half of the patients (p < 0.01), and 15% of these patients experienced the complication of interstitial lung disease (ILD) (p > 0.05). Mean creatine kinase (CK) levels were higher in antibody-positive patients than in antibody-negative patients (p < 0.05). Muscle biopsies were available from 12 anti-HMGCR antibody-positive patients, eight who experienced myofiber necrosis and showed very little or no evidence of inflammatory cell infiltrates in their muscle biopsies. Of these eleven patients who were followed-up 2.5- to 29-month, 73% experienced improvement after treatment. A cross-sectional study showed that anti-HMGCR antibody levels were significantly associated with CK levels (r = 0.486, p = 0.026) as well as with Myositis Disease Activity Assessment (MYOACT) scores (r = -0.67, p = 0.003) during the initial visit. However, changes in serum anti-HMGCR antibody levels did not correlate with changes in CK levels, Manual Muscle Testing 8 (MMT-8) scores or MYOACT scores in long-term follow-up. Conclusion The major clinical features of anti-HMGCR antibody-positive Chinese IIM patients were muscle weakness and dysphagia, which were seen in patients with and without statin exposure. This subtype of patients were responsive to immunosuppressive treatment and received good prognoses after treatment, but serum levels of the anti-HMGCR antibody do not correlate with disease activity.

Clinical characteristics of anti-SAE antibodies in Chinese patients with dermatomyositis in comparison with different patient cohorts.

This study aimed to analyze the clinical features of anti-SAE antibodies in Chinese myositis patients in comparison with different cohorts. The anti-SAE antibodies were tested in myositis patients and in control subjects. Long-term follow-up was conducted on the antibody-positive patients. Anti-SAE antibodies were exclusively present in 12 out of 394 (3.0%) adult dermatomyositis (DM) patients. Of the anti-SAE-positive DM patients, 75% had distinctive diffuse dark-red or pigment-like skin rashes, and 67% of these patients experienced mild muscle weakness. Muscular biopsies showed mild pathological manifestations. Compared with the antibody-negative group, the average age of dermatomyositis onset in the antibody-positive group was higher, and dysphagia occurred more frequently noted (p = 0.012). Only 9 patients received follow-up, 7 experienced improvement after treatment. The anti-SAE antibody levels correlated with improved disease condition. The anti-SAE antibody was found exclusively in adult DM patients, occurring infrequently in Chinese patients. In addition to a diffuse dark-red or pigment-like skin rash and mild muscular weakness, common symptoms included propensity for developing dysphagia. Serum levels of the anti-SAE antibody correlated with myositis disease activity, and anti-SAE-positive patients were responsive to treatment.

Discovery of new biomarkers of idiopathic inflammatory myopathy.

Idiopathic inflammatory myopathies (IIMs) are a group of acquired diseases, characterized by immune-inflammatory processes primarily involving skeletal muscle. According to recent classification criteria, five major diseases have been identified: polymyositis (PM), dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), juvenile idiopathic myositis (JIM) and sporadic inclusion body myositis (sIBM). Although the etiology of IIMs is still incompletely understood, there is much evidence supporting the involvement of genetic, immunological, and environmental factors. In recent years, many new biomarkers have been identified as useful indicators for diagnosis, disease subtypes, prognosis, or response to treatment of IIMs. This article reviews the new biomarkers in serum and muscle tissue, focusing on their pathogenic, diagnostic and prognostic value in IIM. We assigned value based on the categories of myositis specific autoantibodies, cytokines, and genetic markers.

Elevated Serum Levels of Soluble CD163 in Polymyositis and Dermatomyositis: Associated with Macrophage Infiltration in Muscle Tissue

Objective. To investigate serum levels of soluble CD163 (sCD163) in patients with polymyositis (PM) and dermatomyositis (DM), and to correlate these to clinical manifestations and laboratory data. Methods. Serum levels of sCD163 were detected in 24 patients with PM, 84 patients with DM, and 46 healthy controls by using the ELISA method. Immunohistochemistry staining of macrophage infiltration in muscle tissue using anti-CD163 monoclonal antibody was conducted on muscle biopsy specimens from 13 patients with PM and 17 with DM. Results. Serum levels of sCD163 were significantly increased in patients compared with healthy controls (p < 0.001). Patients with interstitial lung disease (ILD) had statistically higher sCD163 levels than patients without ILD (p < 0.001). High serum sCD163 levels were associated with increased incidence of antinuclear antibody (p < 0.05), higher serum levels of immunoglobulin G (p < 0.01) and immunoglobulin A (p < 0.05), and increased erythrocyte sedimentation rates (p < 0.01). Serum sCD163 levels were inversely correlated with CD3+ T cell counts in peripheral blood of patients (r = −0.306, p < 0.01). Cross-sectional assessment and longitudinal study revealed a significant correlation between serum sCD163 levels and disease activity. Patients with high serum sCD163 levels showed a higher incidence of CD163+ macrophage infiltration in muscle tissue than patients with normal sCD163 levels (chi-square value = 10.804, p < 0.01). Conclusion. Serum levels of sCD163 were significantly elevated and correlated with disease severity in patients with PM/DM, suggesting serum sCD163 as a promising biomarker in the disease evaluation of PM/DM. Our finding of elevated serum sCD163 levels associated with muscle macrophage infiltration highlights the role activated macrophage plays in the pathogenesis of PM/DM.

B-cell activating factor as a serological biomarker for polymyositis and dermatomyositis

AIM To investigate serum levels of B-cell activating factor (BAFF) in the patients with polymyositis (PM) and dermatomyositis (DM), and to systematically examine the association between serum BAFF levels and disease activity in PM/DM patients. PATIENTS & METHODS A cross-sectional analysis included 92 PM/DM patients and 25 healthy control subjects. A longitudinal study followed 24 patients. Serum BAFF concentrations were detected by the ELISA method. RESULTS Serum BAFF levels in PM/DM patients were significantly higher than those in healthy controls. A cross-sectional assessment revealed a modest correlation between serum BAFF levels and global disease activity and a mild correlation between serum BAFF levels and muscle disease activity. The longitudinal study showed that serum BAFF levels modestly correlated with global disease activity and muscle disease activity. CONCLUSION Resulting data showed high serum BAFF levels in PM/DM patients and suggested BAFF as a serological biomarker for PM/DM disease activity.

Clinical Profiles and Prognosis of Patients with Distinct Antisynthetase Autoantibodies

Objective. To compare the clinical characteristics and identify the longterm outcomes of Chinese patients with different antisynthetase antibodies. Methods. We investigated retrospectively 124 consecutive patients with antisynthetase syndrome. Medical records, laboratory results, and computed tomography images were obtained. Results. The antisynthetase antibodies we investigated were anti-Jo1 (n = 62), anti-PL7 (n = 31), anti-PL12 (n = 12), and anti-EJ (n = 19). The overall prevalence of interstitial lung disease (ILD) reached 94.4% among study patients. Eleven patients (8.9%) developed rapidly progressive ILD (RP-ILD). Eight patients (6.5%) experienced malignancy. RP-ILD was statistically more prevalent in patients with antisynthetase syndrome with anti-PL7 than those without anti-PL7 (p = 0.028). Anti-Ro52–positive patients with antisynthetase syndrome experienced higher frequency of RP-ILD than those without anti-Ro52 (p = 0.001). Further, anti-PL7–positive patients coexisting with anti-Ro52 exhibited more RP-ILD than those without anti-Ro52 (p = 0.001). Patients with antisynthetase syndrome with RP-ILD had a higher proportion of neutrophils in bronchoalveolar lavage fluid and serum ferritin than those without RP-ILD (p = 0.006 and p = 0.013, respectively). Although no differences were observed between the Kaplan-Meier curves of the 4 antisynthetase antibodies subgroups (p = 0.349), the survival rate of patients with anti-PL7 decreased more rapidly in the early stage of longterm followup compared with those with other antisynthetase antibodies. The presence of RP-ILD, malignancy, and elevated serum ferritin was identified to be associated with poor prognosis in patients with antisynthetase syndrome. Conclusion. Our study investigates the clinical phenotypes and outcomes of patients with antisynthetase syndrome with distinct antisynthetase antibodies and highlights the link between the anti-PL7 antibody and RP-ILD.

Predictive value of serum markers for the development of interstitial lung disease in patients with polymyositis and dermatomyositis: a comparative and prospective study.

Interstitial lung disease (ILD) is one of the most common and devastated complication of polymyositis/dermatomyositis (PM/DM). Several studies have focused on serum biomarkers for ILD in PM/DM patients; however, there have been no prospective studies.

Significant decrease in peripheral regulatory B cells is an immunopathogenic feature of dermatomyositis.

Regulatory B cells (Bregs) are critical in maintaining self-tolerance. Their role in dermatomyositis (DM), an autoimmune disease characterized by inappropriate regulation of hyperactivated B and T cells, has not been clearly defined. In the current study, we performed flow cytometry analysis of studied CD19+ CD24highCD38high Breg subpopulations in blood samples from 30 patients with DM, 37 diseased controls and 23 healthy controls. A significant decrease was observed in the frequency of Bregs in DM patients compared to that in diseased controls (p < 0.0001) and in healthy controls (p < 0.0001). And the prevalence of Bregs deficiency (defined as Bregs/B cells < 0.50% in this study) in DM patients went as high as 73.3%. Furthermore, DM patients with positive myositis specific autoantibody often had lower Bregs levels than negative patients (p = 0.036), and lower level of Bregs was also found in DM patients with interstitial lung disease than in DM patients without (p = 0.041). In a follow-up study, seven DM patients were considered to be in remission stage, and their Breg levels were found to have significantly increased after treatment (p = 0.022). Our research revealed that Breg deficiency is an immunopathogenic feature of DM and provided insights into the design of new immunotherapy target for DM clinical interventions.

Identification of multiple cancer-associated myositis-specific autoantibodies in idiopathic inflammatory myopathies: a large longitudinal cohort study

BackgroundCancer is a significant complication contributing to increased mortality in idiopathic inflammatory myopathies (IIMs), and the association between IIMs and cancer has been extensively reported. Myositis-specific autoantibodies (MSAs) can help to stratify patients into more homogeneous groups and may be used as a biomarker for cancer-associated myositis. In this study, we aimed to systematically define the cancer-associated MSAs in IIMs.MethodsSerum from 627 patients with IIMs was tested for MSAs. The cancer risk with different MSAs was estimated by standardized incidence ratio (SIR). Paraneoplastic manifestation, such as the close temporal relationship between myositis onset and cancer diagnoses in patients with different MSAs, was also evaluated.ResultsCompared with the general Chinese population, patients with IIMs and anti-transcriptional intermediary factor (TIF1)-γ antibodies (SIR = 17.28, 95% CI 11.94 to 24.14), anti-nuclear matrix protein (NXP2) antibodies (SIR = 8.14, 95% CI 1.63 to 23.86), or anti-SAE1 antibodies (SIR = 12.92, 95% CI 3.23 to 32.94), or who were MSAs-negative (SIR = 3.99, 95% CI 1.96 to 7.14) faced increased risk of cancer. There was no association between specific MSAs subtypes and certain types of cancer. Paraneoplastic manifestations were observed in the patients carrying anti-TIF1-γ, as well as other MSAs. There were no prognostic differences among the patients with cancer-associated myositis (CAM) from different MSAs subgroups. However, in comparison to those with cancer unrelated to myositis, CAM had a worse prognosis, with an age-adjusted and sex-adjusted Cox hazard ratio (HR) of 10.8 (95% CI 1.38-84.5, p = 0.02) for all-cause mortality.ConclusionsOur study demonstrates in what is, to our knowledge, the largest population examined to date, that anti-SAE1, and previously reported anti-TIF1-γ and anti-NXP2 antibodies, are all associated with an increased risk of cancer in patients with IIMs. Moreover, our data suggest that in some cases, anti-HMGCR, anti-Jo-1 and anti-PL-12 antibody production might also be driven by malignancy. This can aid in the etiologic research of paraneoplastic myositis and clinical management.