Anti-MDA5 antibody IgG1 subtype is associated with rapidly progressive interstitial lung disease in anti-MDA5-positive dermatomyositis

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Abstract Background Rapidly progressive interstitial lung disease (RP-ILD) is a severe, often fatal complication in patients with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (MDA5 + DM). Early prediction of RP-ILD still remains challenging. We aimed to explore the link between anti-MDA5 IgG subtypes and ILD prognosis in individuals with MDA5 + DM. Methods In a retrospective study involving 71 MDA5 + DM-ILD patients, initial serum titers of anti-MDA5 IgG subtypes were measured using indirect immunofluorescence. We then analyzed the associations between these IgG subclasses and the development of RP-ILD. Result Of the 71 patients, 30% developed RP-ILD. RP-ILD patients had a shorter disease course and a higher mortality rate than non-RP-ILD patients (both P < 0.001). A notable link was found between RP-ILD and anti-MDA5 IgG1 ( P < 0.05), with 100% of RP-ILD patients showing IgG1 titers ≥ 1:100. Additionally, IgG3 positivity was more prevalent in RP-ILD ( P < 0.05). Multivariate logistic regression analysis identified high titers of anti-MDA5 IgG1 and a high neutrophil–lymphocyte ratio (NLR high≥5.22 ) as independent risk factors for RP-ILD ( P = 0.020, 0.017, respectively). The combination of anti-MDA5 IgG1 ≥ 1:100 with an NLR ≥ 5.22 improved the predictive accuracy for RP-ILD, yielding an AUC of 0.80. Conclusions Elevated anti-MDA5 IgG1 titers are strongly related to RP-ILD in MDA5 + DM and function as an important marker for early detection of individuals at high risk. Combining anti-MDA5 IgG1 levels with NLR further enhances predictive accuracy for RP-ILD, offering a practical approach for clinical monitoring and early intervention.

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