Anti-Mi-2 positive interstitial lung disease (ILD): A progressive disease comparable to other myositis-ILD

Evaluation for interstitial lung disease (ILD) often involves sending a myositis panel that includes myositis-associated and myositis-specific antibodies (MAA and MSA respectively) such as anti-Mi-2. Little is known about anti-Mi-2 positive ILD. We sought to determine the typical presentation and prognosis of anti-Mi-2 positive ILD.

We performed a retrospective chart review of patients in two ILD referral centers in Boston, MA with a positive anti-Mi-2 antibody between 2012 and 2024. Patients were identified by query of the medical record for patients with anti-Mi-2, and we included those with ILD on chest computed tomography (CT). We conducted survival analyses for ILD progression-free and overall survival using Kaplan-Meier curves and log-rank tests. Additionally, a Cox proportional-hazards model was employed, adjusting for age, gender, baseline forced vital capacity, and immunosuppressant use to calculate hazard ratios. The comparator group included patients who were followed longitudinally in the ILD clinic who were anti-Mi-2 negative but positive for other MSAs.

Fifty-eight patients were identified. Half (52 %) were female with mean age 67 years (SD 13 years). The majority had dyspnea and/or cough, and a quarter of patients required oxygen upon presentation. Six (10 %) had PM/DM that pre-dated their ILD diagnosis. Other autoantibody positivity was common; one-third-of patients (n = 19, 33 %) were positive for anti-Mi-2 alone without positivity for other MSAs or MAAs. Clinical follow up data were available for 52 patients for a median follow up of 24 months (range <1 month-10 years). PFT progression was seen in 67 % and radiologic progression was seen in over a third. Half received immunosuppression (55 %), with 19 % requiring multiple immunosuppressives. During follow up, 21 % had acute exacerbation of ILD or death. Progression-free and overall survival were not significantly different among anti-Mi-2 positive ILD versus anti-Mi-2 negative, MSA positive ILD patients regardless of anti-Mi-2 positivity alone or in combination with other autoantibodies.

This series of 58 patients is the largest anti-Mi-2 positive ILD cohort to date. Concurrent positivity with other autoantibodies associated with ILD was common. Anti-Mi-2 positive ILD was associated with similar outcomes to those with other MSAs. Larger studies are needed to better characterize patients with Mi-2 positive ILD.