Presence of anti-modified protein antibodies in idiopathic pulmonary fibrosis

Respirology. 2023 Oct;28(10):925-933. doi: 10.1111/resp.14543. Epub 2023 Jun 27.

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.

Keywords: anti-citrullinated peptide; anti-modified protein antibodies; idiopathic pulmonary fibrosis; prognosis; rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid*
  • Autoantibodies / metabolism
  • Fibrinogen / metabolism
  • Filaggrin Proteins
  • Humans
  • Idiopathic Pulmonary Fibrosis*
  • Peptides / metabolism
  • Peptides, Cyclic / metabolism
  • Tenascin / metabolism
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

Substances

  • Autoantibodies
  • Filaggrin Proteins
  • Tenascin
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Peptides, Cyclic
  • Peptides
  • Fibrinogen