Human epididymitis protein 4 as a biomarker of interstitial lung disease in patients with idiopathic inflammatory myopathies

Objective Human epididymis protein 4 (HE4) inhibits the degradation of type I collagen, thus promoting fibrosis. We aimed to investigate serum HE4 levels in patients with idiopathic inflammatory myopathies (IIMs), as potential biomarker of interstitial lung disease (ILD). Methods IIMs patients followed in our centre between June 2020 and January 2023 were enrolled. ILD was detected by high-resolution computed tomography (CT) and pulmonary function tests. Serum HE4 levels were measured in patients and controls. Progressive fibrosing (PF-) ILD was evaluated in patients with available 2-year follow-up (INBUILD criteria). Results We enrolled 90 consecutive IIMs patients (68% females, mean age 59.5 [52.75- 66.0] years) and 42 healthy, age- and sex-matched controls. ILD was diagnosed in 44 (49%) patients. Serum HE4 levels were higher in IIMs patients than controls: 78.55 [54.6-114.4] vs. 51.05 [41.8-62.8] pmol/L (p=0.001). IIMs-ILD patients had higher levels of HE4 vs. those without ILD (193.7 [78.92-137.42] vs. 58.15 [48.32-79] pmol/L, p<0.0001). Serum HE4 levels correlated inversely with diffusing capacity for carbon monoxide (rho=-0.556, p<0.0001) and total lung capacity (rho=-0.459, p=0.001). Serum HE4 levels were the only variable independently associated with IIMs-ILD in two models of multivariate analysis: OR 1.063 (CI 95% 1.02-1.108), p=0.004, and OR 1.059 (CI 95% 1.020-1.099), p=0.003. PF-ILD was detected in 39.4% of IIMs-ILD patients with available follow-up (33/44), without any significant association with baseline serum HE4 levels. Conclusion HE4 might be a useful biomarker in the identification and assessment of ILD in IIMs patients.