Study Of The Relationship Between Red Blood Cell Distribution Width In Dermatomyositis And Polymyositis-Related Interstitial Lung Disease

Objective:Idiopathic inflammatory myopathy(IIM)is a heterogeneous group of autoimmune inflammatory myopathies with common symptoms including muscle pain and muscle fatigue.The main types of the disease include dermatomyositis(DM),polymyositis(PM),inclusion body myositis(IBM),overlap myositis(OM)and immune-mediated necrotic myositis(IMNM),which occur in association with immune system disorders.In this study,we investigated the possible pathological mechanisms of red blood cell distribution width(RDW)in DM and PM-related interstitial lung disease(ILD)by collecting general data,laboratory data and imaging data from patients with idiopathic inflammatory myopathies.The aim was to further investigate the efficacy of RDW-based prediction of concomitant ILD in DM/PM patients.Methods:1.A retrospective cross-sectional study design was used.Data were collected on 124 cases of DM/PM patients initially treated in the Department of Rheumatology and Immunology,First Hospital of Jilin University from June 2018 to December 2021.Receiver operating characteristic curves were made using RDW to distinguish whether DM/PM was combined with ILD to obtain the optimal cut-off value of RDW,and the two groups(elevated and normal groups)were divided into two groups according to the optimal cut-off value of RDW to compare the group differences between the elevated and normal groups of RDW;binary logistic regression analysis was used to determine the factors associated with DM/PM-ILD;the ROC curve was used to assess the predictive value of the factors associated with DM/PM-ILD.2.To clarify the relationship between RDW and lung function in DM/PM-ILD,this study used a controlled study of 20 patients with DM/PM-ILD with longitudinal follow-up.Results:(1)A total of 124 patients were included in the retrospective crosssectional study,aged 18-74 years,with a median age of 52 years(40-60years),39 males(31.5%),and 85 females(68.5%).According to the diagnostic and classification criteria for myositis released by the European League Against Rheumatism/American College of Rheumatology(EULAR/ACR)in 2017,76 patients were diagnosed with DM(61.3%)and48 patients with PM(38.7%).42 patients had ILD(33.9%),including 27 in the DM group and 15 in the PM group,and there was no significant difference in the ILD incidence rate between the DM group and the PM group(P > 0.05).Subgroup analysis results showed that PM patients are more likely to experience fatigue(P = 0.005),and the rashes(heliotrope,erythematous patches,Gottron rash)only appeared in DM patients(P <0.001).The total cholesterol(TC)level of PM patients was significantly higher than that of DM patients(P = 0.027),and the creatine kinase(CK)and alanine aminotransferase(ALT)levels were significantly higher than those of DM patients(P < 0.001).All patients underwent myositis antibody spectroscopy,of which 74(59.7%)had positive myositis specific autoantibodies(MSAs),and 56(45.2%)had positive myositis associated autoantibodies(MAAs),and 18(14.5%)were positive for anti-MDA5 antibodies and anti-Jo-1 antibodies,respectively.Anti-MDA5 antibodies(P < 0.001)and anti-TIF1γ antibodies(P = 0.034)were only detected in DM patients.In addition,one patient was detected with coexistence of antiJo-1,anti-MDA5 and anti-NXP2 antibodies,and one patient was detected with coexistence of anti-EJ and anti-Mi2 antibodies.(2)Patients with DM/PM were divided into DM/PM-ILD and DM/PM-non-ILD groups according to whether there was complicated ILD.Subgroup analysis showed that fever and arthritis were more common in the DM/PM-ILD patients(P = 0.010,P < 0.001),while myalgia was more common in the DM/PM-non-ILD group(P = 0.043).The frequency of inflammatory cell infiltration was lower in the DM/PM-ILD group(P =0.010).The levels of CK,AST,ALT,TC and LDL-C in the DM/PM-ILD group were significantly lower than those in the non-ILD group(P < 0.05);on the contrary,the RDW(13.9(13.0-15.8)vs.13.3(12.7-14.1),P = 0.012)and Ig M levels(P = 0.039)in the DM/PM-ILD group were significantly higher than those in the DM/PM-non-ILD group.Compared with the DM/PM-non-ILD group,the detection rate of myositis antibodies such as anti-MDA5 antibodies,anti-Jo-1 antibodies and anti-Ro52 antibodies were significantly higher in the DM/PM-ILD group(P < 0.001).(3)Subgroup analysis of RDW showed that myalgia was more common in the RDW normal group(P = 0.012),while ILD was more common in the RDW high group(P = 0.009).In the RDW high group,hypersensitive C-reactive protein(hs CRP)was significantly higher than the RDW normal group(P = 0.027).Compared with the RDW normal group,the level of complement 4(C4)was lower in the RDW high group(P = 0.036).(4)Univariate and multivariate binary logistic regression analysis found that in addition to anti-MDA5 and anti-Jo-1 antibodies and other recognized independent risk factors,Elevated RDW values are an independent risk factor for DM/PM-ILD(OR = 1.635,95%CI 1.172-2.281,P = 0.004,RDW as a continuous numerical variable;OR = 3.145,95%CI1.079-9.168,P = 0.036,RDW as a dichotomous variable).(5)RDW(dichotomous variable)combined with anti-MDA5 antibody plotted the ROC curve for DM/PM-ILD,showing an AUC of0.723(95% CI 0.626-0.820),sensitivity of 73.8%,specificity of 64.6%,positive predictive value of 72.2%,and negative predictive value of 72.6%for this model;RDW(dichotomous variable)combined with anti-Jo-1antibody in combination with anti-Jo-ILD showed an AUC of 0.731(95%CI 0.634-0.829),sensitivity of 73.8%,specificity of 63.4%,positive predictive value of 77.8% and negative predictive value of 73.6%.ROC curves for DM/PM-ILD with RDW(continuous numerical variables)in combination with anti-MDA5 antibody showed an AUC of0.743(95% CI 0.646-0.839),sensitivity of 54.8%,specificity of 87.8%,positive predictive value of 69.2% and negative predictive value of 75.5%;RDW(continuous numerical variables)in combination with anti-Jo-1antibody showed an AUC of 0.736(95% CI 0.633-0.840),sensitivity of 54.8%,specificity of 90.2%,positive predictive value of 74.1% and negative predictive value of 78.9%.(6)A total of 20 cases of DM/PM-ILD were included in the study results: all 20 patients had some impairment in diffusing lung function(manifested as DLCO < 80%)at baseline,and after administration of the treatment,RDW values decreased as diffusing lung function improved at the third month of follow-up(P = 0.016).Among the 20 patients,three patients had further aggravation of pulmonary impairment at the third month of follow-up,including two patients who also had a further increase in RDW value and one patient who had no significant change in RDW value.Conclusion:(1)RDW combined with anti-MDA5 antibody or anti-Jo-1 antibody was a significant predictor of DM/PM-ILD.(2)RDW was associated with DM/PM-ILD and patients with DM/PM-ILD had higher RDW values compared to patients without ILD,which varied with lung function.