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Objective:To explore the independent risk factors and early diagnosis of dermatomyositis (DM) with positive anti-melanoma differentiation associated gene 5 (MDA5) antibody.Methods:A total of 223 DM patients admitted to the Department of Rheumatology and Immunology, Affiliated Hospital of Xuzhou Medical University from January 2012 to June 2021 were retrospectively analyzed, according to whether the anti-MDA5 antibody was positive or not, the patients were divided into anti-MDA5 antibody positive group ( n= 34) and anti-MDA5 antibody negative group ( n=189). The demographic data, clinical manifestations and laboratory test results of the two groups were compared. The risk factors of DM patients with positive anti-MDA5 antibody were analyzed by binary Logistic regression, and the receiver operating characteristic curve (ROC) was drawn to evaluate the predictive value of various risk factors for anti-MDA5 antibody positive DM patients. Results:The incidence of skin ulcer [20.6%(7/34) vs 9.0%(17/189), χ2=4.03, P=0.045], the positive rate of anti-Ro52 antibody [61.8%(21/34) vs 21.2%(40/189), χ2=23.90, P<0.001], the incidence of interstitial lung disease (ILD) [91.2% (31/34) vs 38.6%(73/189), χ2=31.98, P<0.001] and rapidly progressive interstitial lung disease (RP-ILD) [67.6%(23/34) vs 5.3%(10/189), χ2=88.87, P<0.001], the levels of D-dimer [1.87(1.23, 2.56) μg/ml vs 1.15(0.59, 1.29) μg/ml, χ2=4.68, P<0.001] and serum ferritin (SF) [931.65(579.12, 1 160.43) ng/ml vs 507.40(200.40, 588.55) ng/ml, χ2=5.60, P<0.001] in the anti-MDA5 antibody positive group were higher than those in the anti-MDA5 antibody negative group, wherease the creatine kinase (CK) level in the anti-MDA5 anti-body positive group was significantly lower than that in the anti-MDA5 antibody negative group [85.50(61.25, 1 55.00) U/L vs 263.00(66.50, 1 111.14) U/L, χ2=3.08, P=0.002]. Multivariate Logistic regression analysis showed that positive anti-Ro52 antibody [ OR(95% CI)=5.027(1.632, 15.483), P=0.005], increased D-dimer level [ OR(95% CI)=1.665(1.124, 2.466), P=0.011], occurrence of ILD [ OR(95% CI)=10.071(2.061, 49.207), P=0.004] and RP-ILD[ OR(95% CI)=10.91(3.294, 36.134), P<0.001] were independent risk factors for anti-MDA5 antibody positive DM patients. The ROC curve showed that the areas under the curve (95% CI) of anti-Ro52 antibody, D-dimer, ILD and RP-ILD were 0.703(0.615, 0.791), 0.752(0.661, 0.843)], 0.763(0.703, 0.822), 0.812(0.730, 0.893) respectively. The P value of all these parameters were <0.001 and their value in predicting anti-MDA5 antibody positive DM was high. Conclusion:Positive anti-Ro52-Ab, increased D-dimer level, presence of ILD and RP-ILD are independent risk factors for anti-MDA5 antibody positive DM patients, and they have certain early diagnostic value for DM patients with positive anti-MDA5 antibody.
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Objective:To investigate the high resolution computed tomography (HRCT) findings, laboratory test results and clinical manifestations of anti-melanoma differentiation-associated gene 5 (MDA5) antibody positive dermatomyositis complicated with lung interstitial lesions, and to analyze the correlation between the HRCT findings and clinical course of disease.Methods:Twenty-seven patients with anti-MDA5 antibody positive associated dermatomyositis (DM) were included and divided into two groups: acute/subacute group ( n=15) and chronic group ( n=12). HRCT images of lung were analyzed. Clinical data including gender, age, clinical manifestations and course of disease, anti-Ro52 antibody, creatine kinase (CK), antinuclear antibody (ANA), anti-Jo-1 antibody and erythrocyte sedimentation rate (ESR) were also collected. χ2 test was adopted for statistical analysis. Results:① Interstitial changes were 100%(27/27). The proportion of unilateral localized distribution was the most [48%(13/27)], followed by bilateral localized distribution [30%(8/27)], and bilateral diffuse distribution [22%(6/27)). ② Among the HRCT findings of lung interstitial changes, ground glass shadow was the most common presentations [59%(16/27)], followed by subpleural curve sign [63%(17/27)] and interlobular septal thickening [56%(15/27)], while honeycomb sign [0(0/27)] had the lowest rate of presentation. ③ Compared with the chronic progressive group, the acute/subacute progressive group presented as chest tightness (80% vs 8%, χ2=13.715, P<0.05) and dyspnea (47% vs 0, χ2=7.560, P<0.05). Acute/subacute HRCT showed ground glass opacity (87% vs 25%, χ2=10.501, P<0.05). The prominent HRCT showed interlobular septal thickening in the chronic course group (83% vs 33%, χ2=6.750, P<0.05). ④ The anti-MDA5 antibody (+++) index was significantly different (88% vs 25%, χ2=8.168, P<0.05). There was no significant difference in anti-Ro52 antibody (+), ANA(+), anti-Jo-1 antibody(+), CK elevation and ESR elevation between the two groups ( P>0.05). Conclusion:Most dermatomyositis patients with positive anti-MDA5 antibody are complicated with interstitial lung lesions, the HRCT manifestations of lung are diverse. In order to confirm the diagnosis of this disease, clinical manifestations, laboratory and pathological examinations are required.
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Objective:To clarity the clinical features of juvenile dermatomyositis (JDM) with positive anti-melanoma differentiation associated gene 5 (MDA5) antibody.Methods:Retrospective study.Clinical data of 11 anti-MDA5 autoantibody-positive JDM patients in the Department of Rheumatology and Immunology, Children′s Hospital Affiliated to Capital Institute of Pediatrics from January 2016 to January 2019 were retrospectively recruited for analyzing their clinical characteristics, pulmonary imaging and pulmonary function, thus summarizing treatment experiences.Results:A total of 11 children with anti-MDA5 autoantibody-positive JDM were recruited, involving 2 males and 9 females, with the average onset age of 1-13 (5.8±4.2) years.Clinical manifestations included rash in 11 cases (100.0%), arthritis in 5 cases (45.5%), and myasthenia in 4 cases (36.4%). Muscle enzyme elevated in 10 cases (90.9%) and serum ferritin (SF) elevated in 9 patients (81.8%). Ten cases (90.9%) showed interstitial lung disease (ILD), manifesting as ground glass opacity at subpleural area on CT scans, restrictive ventilation and decreased diffusion function on lung function test, while respiratory symptoms were absent.All patients were treated with glucocorticoid combined with immunosuppressor.Case 2 developed into rapid progressive pulmonary interstitial disease (RPILD), and died of respiratory failure 2 months later.The remaining was followed up for 1-2 years, and the ILD was relieved.Conclusions:All recruited children with anti-MDA5 autoantibody-positive JDM presented typical rash, and mild muscle weakness with a greater tendency to arthritis.Chinese pediatric patients are prone to complicate with ILD with no respiratory symptoms, but ground glass opacity at subpleural area on CT, and restrictive ventilation and decreased diffusion function on lung function test can be detected.Elevated SF is associated with the development of ILD.Glucocorticoid combined with immunosuppressive therapy is effective to JDM with ILD, but ineffective for RPILD.The mortality of anti-MDA5 autoantibody-positive JDM is high without an effective treatment.
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Objective The current meta-analysis was performed to update the evidcnce on anti-melanoma differentiation-associated gene 5 (MDA5) antibody for the diagnosis of rapid progressive interstitial lung disease (RPILD) and chronic ILD in adult or juvenile dermatomyositis (JDM).Methods The electronic search on PubMed,Embase,Cochrane Library,CNKI,WangFang Data,VIP and China Biology Medicine database was conducted from their inception to May,2017.Meta-disc1.4 was used to calculate heterogeneity and obtain the pool sensitivity,specificity,diagnostic odds ratio,positive and negative likelihood ratios and summarized receiver operating characteristic (SROC) curve.Quality assessment and publication bias were determined by QUADAS-2 and STATA 12.0.Results A total of 32 studies with high quality and middle heterogeneity were selected for the final data synthesis.Anti-MDA5 showed a higher diagnostic and prognostic value for RPILD (AUC =0.927,Q * =0.862),compared with chronic ILD (AUC =0.717,Q * =0.667) in adult dermatomyositis patients.For diagnosing RPILD in JDM,the value of MDA5 detection (AUC =0.836,Q * =0.768)was weak.For the prediction of RPILD,the validity of anti-MDA5 detection in clinical amyopathic dermatomyositis (CADM) (AUC =0.942,Q* =0.880) was higher than that in DM (AUC =0.926,Q * =0.860),which was also more applicable to East-Asia populations (AUC =0.960,Q* =0.891),compared with Chinese (AUC =0.925,Q* =0.859) and Western populations (AUC =0.928,Q* =0.863).The methodological assessment for different anti-MDA5 detection implied ELISA (AUC =0.929,Q* =0.864) was superior in performance as immunoprecipitation (AUC =0.927,Q* =0.859),and there was no publication bias according to Deek's plot.Conclusion Anti-MDA5 antibody should be a significant laboratory index for diagnosis and prediction of ILD in adult DM and JDM with high sensitivity and specificity.
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Objective To investigate the association of human leucocyte antigen (HLA-DRB1) with anti-melanoma differentiation-associated gene 5 (MDA5) expression in polymyositis/dermatomyositis (PM/DM).Methods Seventy patients with PM,104 patients with DM and 400 healthy controls were included.Genotyping of HLA-DRB1 was performed using the sequencing-based typing method.Levels of anti-MDA5 were measued by enzyme linked immunosorbent assay using recombinant MDA5 antigen.The frequencies of HLA-DRB1 alleles were compared between the patients and controls using a chi-square test or Fisher's exact test.Results Frequencies of DRB1 * 04∶01 [17.0％ vs 1.3％,corrected P-value (Pc)=3.8×10-8;odds ratio (OR)=16.2;95％ confidence interval (CI) (6.6,39.7)] and DRB1 * 12∶02 [(42.6％ vs 19.3％,Pc=0.008;OR=3.1;95％ CI(1.7,5.7)] were significantly higher in anti-MDA5 positive PM/DM patients compared with the controls.The frequencies of DRB1 * 04∶01 [P=5.2×10-6,OR=17.1,95％CI:(5.3,54.9)\ and * 12∶02 [P=3.8×10-4,OR=3.1,95％CI(1.7,5.7)] in anti-MDA5 positive DM-interstitial lung disease (ILD) patients were higher than those in the controls,whereas the frequencies of DRB1 * 04∶01 and * 12∶02 did not differ between the anti-MDA5 negative DM-ILD patients and the controls.No difference in the frequency of DRB1 alleles,other than * 04∶01,carrying the shared epitope (SE),i.e.* 01∶01,* 01∶02,* 04∶05 and * 10∶01,was observed between the controls and DM patients stratified by the presence of anti-MDA5 and ILD.Conclusion DRB1 * 04∶01 and * 12∶02 confer susceptibility to anti-MDA5 antibody production in DM,which cannot be explained by the SE hypothesis.