Anti-MDA5 antibody-positive dermatomyositis: pathogenesis and clinical progress

Lu, Xin; Peng, Qinglin; Wang, Guochun

doi:10.1038/s41584-023-01054-9

Cited by 15 publications

(20 citation statements)

References 181 publications

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“…Hyperferritinaemia has been recognized as an independent risk factor for poor prognosis in patients with anti-MDA5 + IIM-ILD ( 35 , 49 , 54 ) and in those with ASS-ILD ( 55 ). Ferritin is associated with macrophage activation ( 56 ). Our study revealed the predictive value of hyperferritinaemia for PF-ILD in patients with ASS.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of natural killer cell depletion in predicting progressive fibrosing interstitial lung disease in idiopathic inflammatory myopathies

Shao,

Xia,

Zhen

et al. 2024

Front. Immunol.

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ObjectivesInterstitial lung disease (ILD) is one of the common extramuscular involvement in idiopathic inflammatory myopathies (IIMs) (1). Several patients develop a progressive fibrosing ILD (PF-ILD) despite conventional treatment, resulting in a progressive deterioration in their quality of life (2). Here, we investigated the clinical and immune characteristics of IIM-ILD and risk factors for PF-ILD in IIM, mainly in anti-melanoma differentiation-associated protein 5 (anti-MDA5+) dermatomyositis (DM) and anti-synthetase syndrome (ASS).MethodsHere, a prospective cohort of 156 patients with IIM-ILD were included in the longitudinal analysis and divided into the PF-ILD (n=65) and non-PF-ILD (n=91) groups, and their baseline clinical characteristics were compared. Univariate and multivariate Cox analyses were performed to identify the variables significantly associated with pulmonary fibrosis progression in the total cohort, then anti-MDA5+ DM and ASS groups separately.ResultsPeripheral blood lymphocyte counts, including T, B, and NK cell counts, were significantly lower in the PF-ILD group than in the non-PF-ILD group. This characteristic is also present in the comparison between patients with anti-MDA5+ DM and ASS. The multivariate Cox regression analysis revealed that age > 43.5 years [HR: 7.653 (95% CI: 2.005-29.204), p = 0.003], absolute NK cell count < 148 cells/μL [HR: 6.277 (95% CI: 1.572-25.067), p = 0.009] and absolute Th cell count < 533.2 cells/μL [HR: 4.703 (95% CI: 1.014-21.821), p = 0.048] were independent predictors of progressive fibrosing during 1-year follow-up for patients with anti-MDA5+ DM, while absolute count of NK cells < 303.3 cells/µL [HR: 19.962 (95% CI: 3.108-128.223), p = 0.002], absolute count of lymphocytes < 1.545×109/L [HR: 9.684 (95% CI: 1.063-88.186), p = 0.044], and ferritin > 259.45 ng/mL [HR: 6 (95% CI: 1.116-32.256), p = 0.037] were independent predictors of PF-ILD for patients with ASS.ConclusionsPatients with anti-MDA5+ DM and ASS have independent risk factors for PF-ILD. Lymphocyte depletion (particularly NK cells) was significantly associated with PF-ILD within 1-year of follow-up for IIM-ILD

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Section: Discussionmentioning

confidence: 99%

Prognostic significance of natural killer cell depletion in predicting progressive fibrosing interstitial lung disease in idiopathic inflammatory myopathies

Shao,

Xia,

Zhen

et al. 2024

Front. Immunol.

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“…Skin ulceration and palmar papules are typical skin features of anti-MDA5 positive DM. 5 , 6 The prevalence of ILD reported in anti-MDA5 positive DM ranged from 50 to 100%. 7 …”

Section: Introductionmentioning

confidence: 99%

Liver Involvement is Associated with Higher Risk of Rapidly Progressive Interstitial Lung Disease and Mortality in Anti-Melanoma Differentiation-Associated Gene 5 Antibody- Positive Dermatomyositis

Yang,

Cui,

Yang

et al. 2024

JIR

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Purpose This study aimed to assess liver involvement and investigate its correlation with rapidly progressive interstitial lung disease (RP-ILD) and mortality in anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5 positive) DM patients. Patients and Methods This retrospective study included 159 patients diagnosed with anti-MDA5 positive DM or anti-synthetase syndrome (ASyS). Clinical features and laboratory findings were compared between patients with anti-MDA5 positive DM and patients with ASyS. In the anti-MDA5 positive DM cohort, clinical features and laboratory findings between patients with liver involvement and without liver involvement were further compared. The effects of liver involvement on the overall survival (OS) and development of RP-ILD were also analyzed using Kaplan–Meier method and Cox regression analysis. Results Levels of serum aspartate aminotransferase (AST), alanine transaminase (ALT), γ-glutamyl transferase (γGT) and alkaline phosphatase (ALP) were all significantly higher in patients with anti-MDA5 positive DM than those in patients with ASyS. In our cohort of anti-MDA5 positive DM patents, 31 patients (34.4%) were complicated with liver involvement. Survival analysis revealed that serum ferritin >1030.0 ng/mL (p<0.001), ALT >103.0 U/l (p<0.001), AST >49.0 U/l (p<0.001), γGT >82.0 U/l (p<0.001), ALP >133.0 U/l (p<0.001), lactate dehydrogenase (LDH)>474.0 U/l (p<0.001), plasma albumin (ALB) <35.7 g/l (p<0.001) and direct bilirubin (DBIL) >2.80 μmol/l (p=0.002) predicted poor prognosis. The incidence of RP-ILD increased remarkably in patients with liver involvement compared to patients without liver involvement (58.1% vs 22.0%, p=0.001). Multivariate analysis revealed that elevated serum ALT level was an independent risk factor for mortality (HR 6.0, 95% CI 2.3, 16.2, p<0.001) and RP-ILD (HR 5.9, 95% CI 2.2, 15.9, p<0.001) in anti-MDA5 positive DM patents. Conclusion Liver involvement is common in patients with anti-MDA5 positive DM. Elevated serum ALT level was an independent risk factor for RP-ILD and mortality in patients with anti-MDA5 positive DM.

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“…Anti-MDA5 positive dermatomyositis (MDA5+ DM) is a type of idiopathic inflammatory myopathy with positive MDA5 autoantibody, involvement of multiple organs, heterogeneous clinical spectrum of manifestations, and high mortality ( 1 , 2 ). The high mortality rate means that MDA5+ DM is a substantial challenge for clinical rheumatologists.…”

Section: Introductionmentioning

confidence: 99%

“…The identification of endotypes could provide deeper insights into the underlying pathological mechanisms to guide clinical management and therapeutic development. Although the aetiology and pathology remain unclear, increasing evidence suggests that multiple factors, including T cells, B cells, neutrophils and macrophages, are implicated in the pathophysiology of MDA5+DM ( 2 ). The inclusion of calcineurin inhibitors (cyclosporine A, tacrolimus) in several immunosuppressive regimens indicates that targeting T cells is an effective means to treat MDA5+ DM ( 3 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, recent studies showed MDA5+ DM patients with co-existing anti-Ro52 antibodies had an increased frequency of RPILD and more aggressive phenotypes, highlighting the breach of B cell tolerance likely contributes to the pathogenesis in MDA5+ DM ( 13 , 14 ). B cell depletion with rituximab has been used to treat dermatomyositis ( 15 ), which could be an alternative treatment for MDA5-DM in severe and refractory cases ( 2 ). Studies have also shown that both monocytes and lymphocytes are correlated with different prognoses of MDA5+ DM ( 16 , 17 ).…”

Section: Introductionmentioning

confidence: 99%

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Disease-associated immune cell endotypes in anti-MDA5-positive dermatomyositis using unbiased hierarchical clustering

Guo,

Yang,

et al. 2024

Front. Immunol.

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ObjectiveClinical and prognostic features of Anti-MDA5-Positive Dermatomyositis (MDA5+ DM) are diverse. This study aimed to examine the peripheral immune cell profiles of patients with MDA5+ DM, identify disease endotypes related to the heterogeneous manifestations and prognosis, and guide individualized therapy regimen.MethodsThis inpatient cohort included 123 patients with MDA5+ DM. Unsupervised hierarchical clustering analysis was used to derive disease endotypes from the circulating immune cell profiles on admission. Clinical symptoms, laboratory test results, inpatient treatments, and disease outcomes were then analyzed among the identified endotypes.ResultsThree disease endotypes in MDA5+ DM were identified from peripheral immune cell profiles. Endotype1 had the highest percentages of CD4+ T cells and monocytes, and the lowest percentage of neutrophils; Endotype2 had the highest percentage of B cells; Endotype3 had the highest percentage of CD8+ T cells and NK cells. Clinical and prognostic heterogeneity of the endotypes were revealed. Endotype1 had the lowest 3-month mortality with the high incidence of periungual capillary changes. Endotype2 and Endotype3 had higher prevalence of rapidly progressive interstitial lung disease (RPILD) and mortality at 3 months than Endotype1. Meanwhile, Endotype3 had higher pneumocystis jiroveci and CMV viremia cases with significantly elevated of activated CD8+ T cells and multiple cytokines than Endotype1.ConclusionClustering analysis of peripheral immune cell profiles identified three different endotypes in MDA5+ dermatomyositis. Endotpye2 and 3 showed higher RPILD, 3-month mortality, pneumocystis jiroveci and CMV viremia.

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Anti-MDA5 antibody-positive dermatomyositis: pathogenesis and clinical progress

Cited by 15 publications

References 181 publications

Prognostic significance of natural killer cell depletion in predicting progressive fibrosing interstitial lung disease in idiopathic inflammatory myopathies

Prognostic significance of natural killer cell depletion in predicting progressive fibrosing interstitial lung disease in idiopathic inflammatory myopathies

Liver Involvement is Associated with Higher Risk of Rapidly Progressive Interstitial Lung Disease and Mortality in Anti-Melanoma Differentiation-Associated Gene 5 Antibody- Positive Dermatomyositis

Disease-associated immune cell endotypes in anti-MDA5-positive dermatomyositis using unbiased hierarchical clustering

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