Presence of anti‐modified protein antibodies in idiopathic pulmonary fibrosis

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Abstract Background and Objective Studies of autoimmunity and anti‐citrullinated protein antibodies (ACPA) in idiopathic pulmonary fibrosis (IPF) have been confined to investigations of anti‐cyclic citrullinated peptide (anti‐CCP) antibodies which utilize synthetic peptides as surrogate markers for in vivo citrullinated antigens. We studied immune activation by analysing the prevalence of in vivo anti‐modified protein antibodies (AMPA) in IPF. Methods We included patients with incident and prevalent IPF (N = 120), sex and smoking‐matched healthy controls (HC) (N = 120) and patients with RA (N = 104). Serum (median time: 11 months [Q1–Q3: 1–28 months] from diagnosis) was analysed for presence of antibodies towards native and posttranslational modified (citrullinated [Cit, N = 25]; acetylated [Acet, N = 4] and homocitrullinated [Carb, N = 1]) peptides derived from tenascin (TNC, N = 9), fibrinogen (Fib, N = 11), filaggrin (Fil, N = 5), histone (N = 8), cathelicidin (LL37, N = 4) and vimentin (N = 5) using a custom‐made peptide microarray. Results AMPA were more frequent and in increased levels in IPF than in HC (44% vs. 27%, p < 0.01), but less than in RA (44% vs. 79%, p < 0.01). We specifically observed AMPA in IPF towards certain citrullinated, acetylated and carbamylated peptides versus HC: tenascin (Cit(2033)‐TNC2025–2040; Cit(2197)‐TNC2177–2200; Cit(2198)‐TNC2177–2200), fibrinogen (Cit(38,42)‐Fibα36–50; Cit(72)‐Fibβ60–74) and filaggrin (Acet‐Fil307–324, Carb‐Fil307–324). No differences in survival (p = 0.13) or disease progression (p = 0.19) between individuals with or without AMPA was observed in IPF. However, patients with incident IPF had better survival if AMPA were present (p = 0.009). Conclusion A significant proportion of IPF patients present with specific AMPA in serum. Our results suggest autoimmunity as a possible characteristic for a subgroup of IPF that may affect disease outcome.

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