Although it remains unclear whether HE4 is implicated in the pathogenesis of RA-ILD, LeBleu et al. have showed that HE4 can suppress the activity of multiple proteases, including serine proteases and matrix metalloproteinases, and specifically inhibits their capacity to degrade type I collagen, thereby promoting the development of kidney fibrosis (18). This evidence concerns the gene WFDC2 and rheumatoid arthritis.