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

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.

Keywords: Anti-MDA5 antibody; IgG1; Indirect immunofluorescence; Rapidly progressive interstitial lung disease.

Fig. 1

Distribution of anti-MDA5 IgG subclasses in MDA5⁺ DM-ILD patients. A Proportions of anti-MDA5 IgG subclasses (IgG1, IgG2, IgG3, and IgG4) at an antibody titer threshold of 1:10 across 71 MDA5⁺ DM-ILD patients. B Comparison of the prevalence of anti-MDA5 IgG subclasses between 21 patients with rapidly progressive ILD (RP-ILD) and 50 patients with non-RP-ILD. A titer of 1:10 or greater is considered positive for anti-MDA5 IgG subclasses

Fig. 2

Profiles of anti-MDA5 IgG subclass combinations in RP-ILD and non-RP-ILD patients. A Distribution of anti-MDA5 IgG1, IgG2, IgG3, and IgG4 titers at ≥ 1:100 across the 71 MDA5⁺ DM-ILD patients. B Different combinations of anti-MDA5 IgG subclasses present in RP-ILD versus non-RP-ILD patients. Bar chart displays patient numbers for each subclass combination group

Fig. 3

Diagnostic value of anti-MDA5 IgG1 in combination with key laboratory indicators in predicting RP-ILD. A Receiver Operating Characteristic (ROC) curves showing the Area Under the Curve (AUC) for the predictive power of anti-MDA5 IgG1 combined with the neutrophil–lymphocyte ratio (NLR), C-reactive protein (CRP), serum ferritin (SF), anti-Ro52 antibody (Ro52), or anti-MDA5 IgG1 alone (≥ 1:100) for RP-ILD development. B Survival analysis using the wilcoxon test to compare RP-ILD outcomes in patients with high anti-MDA5 IgG1 in combination with NLR, CRP, SF, Ro52, or high anti-MDA5 IgG1 alone (≥ 1:100) versus low anti-MDA5 IgG1 (< 1:100). ^*P < 0.05, ^**P < 0.01