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Presence of anti-modified protein antibodies in idiopathic pulmonary fibrosis.

Authors :: Kalafatis D
Joshua V
Hansson M
Mathsson-Alm L
Hensvold A
Sköld M
Source :: Respirology (Carlton, Vic.) [Respirology] 2023 Oct; Vol. 28 (10), pp. 925-933. Date of Electronic Publication: 2023 Jun 27.
Publication Year :: 2023
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.<br />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.<br />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 <subscript>(2033)</subscript> -TNC <subscript>2025-2040</subscript> ; Cit <subscript>(2197)</subscript> -TNC <subscript>2177-2200</subscript> ; Cit <subscript>(2198)</subscript> -TNC <subscript>2177-2200</subscript> ) <subscript>,</subscript> fibrinogen (Cit <subscript>(38,42)</subscript> -Fibα <subscript>36-50</subscript> ; Cit <subscript>(72)</subscript> -Fibβ <subscript>60-74</subscript> ) and filaggrin (Acet-Fil <subscript>307-324</subscript> , Carb-Fil <subscript>307-324</subscript> ). 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).<br />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.<br /> (© 2023 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)