Clinical Studies Of Organ Involvement And Human Leukocyte Antigen-G Expression In Polymyositis/Dermatomyositis

Objective Idiopathic inflammatory myopathy (IIM) is a heterogeneous group of systemic autoimmune diseases of unknown pathogenesis, including polymyositis (PM) and dermatomyositis (DM) as two common subtypes. The aims of this study are to investigate the clinical features of PM/DM patients with gastrointestinal involvement and thyroid dysfunction. Then we preliminaryly examined human leukocyte antigen-G (HLA-G) expression in PM/DM and its correlation with disease activity to determine its role in the pathogenesis of the disease.Methods In the first part of this study, we retrieved and filtered literature about prevalence and drug therapy of PM/DM patients with gastrointestinal involvement, and then conducted a meta-analysis and systematic reviews. In the second part, a retrospective analysis of204PM/DM patients was conducted to find out the clinical and immunological characteristics of PM/DM patients with thyroid dysfunction and autoimmune thyroid disease (AITD). In the third part of the study, HLA-G expression in the serum samples, peripheral blood lymphocytes and muscle biopsies were determined by enzyme-linked immunosorbent assay(ELISA), flow cytometry and immunohistochemistry respectively in96PM/DM patients.Results In the first part of this study, a total of23articles were included, which included1719patients. The pooled prevalence of esophageal involvement was47%(95%CI43.5-50.4%). Dysphagia was the most frequently reported symptom with a prevalence of31%(95%CI26.9-35.2%). There was no significant difference in the prevalence of esophageal involvement or dysphagia between PM and DM. Aspiration pneumonia secondary to esophageal involvement is the main cause of death in PM/DM patients with esophageal involvement with a prevalence of8.8%(95%CI11.2-13.8%). IVIG therapy showed excellent efficacy in patients with life-threatening steroid-resistant gastrointestinal involvement.In the second part,47.5%of204PM/DM patients had thyroid dysfunction. The most common subgroup of thyroid dysfunction is euthyroid sick syndrome (ESS)(34.3%), followed by hypothyroidism(8.3%) and hyperthyroidism (4.4%). PM/DM patients with ESS were prone to have higher incidence of arthritis, fever, interstitial lung disease (ILD) and blood system damage, as well as higher levels of C-reactive protein(CRP), erythrocyte sedimentation rate(ESR), ferritin, and lower level of hemoglobin(HGB)(P<0.05). The ESS subgroup showed a higher incidence of deaths(P<0.05). The subgroup with hypothyroidism were with higher levels of cholesterol(CHO), thyroid peroxidase antibodies(TPOAb) and thyroglobulin antibodies(TGAb)(P<0.05). The hyperthyroidism group had a significant higer level of CHO(P<0.05). The incidence of PM/DM associated with AITD was5.4%. The most commonly seen AITD was Hashimoto’s thyroiditis(HT)(4.4%).The third part indicated that Serum sHLA-G levels were significantly higher in PM/DM patients than that observed in the controls (43.96±70.20U/ml vs.4.22±5.13U/ml; P<0.001). Additionally, a positive correlation was observed between sHLA-G levels and the MYOACT-global disease activity score of the PM/DM patients (r=0.732; P<0.001). The expression of HLA-G in peripheral CD4+T lymphocytes (4.45%±3.60%vs.1.65%±1.40%; P=0.002) and CD8+T lymphocytes (4.33%±3.41%vs.1.40%±1.64%; P=0.001) from24PM/DM patients was higher than that in the controls. Furthermore, HLA-G molecules were detected in63%of muscle biopsies from35patients with PM/DM, whereas no control sample expressed HLA-G.Conclusion The first part of this study revealed that esophageal involvement is a common complication in PM/DM patients, mainly manifested as dysphagia. Aspiration pneumonia secondary to esophageal involvement is the main cause of death in this subtype of PM/DM patients. IVIG combined with glucocorticoids and immunosuppressant is effective against gastrointestinal damage. The second part of our study indicated that thyroid dysfunction is common in PM/DM. ESS was most frequently seen and exhibited a higher incidence of deaths. The most commonly seen AITD associated with PM/DM is HT. The third part of this study demonstrated that HLA-G was higher in PM/DM patients and correlated with disease activity, which allow HLA-G to potentially act as a useful disease activity marker for clinical practice.