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


Journal

Respirology (Carlton, Vic.)
ISSN: 1440-1843
Titre abrégé: Respirology
Pays: Australia
ID NLM: 9616368

Informations de publication

Date de publication:
10 2023
Historique:
received: 16 12 2022
accepted: 19 06 2023
medline: 19 9 2023
pubmed: 28 6 2023
entrez: 28 6 2023
Statut: ppublish

Résumé

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. 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. 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 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.

Sections du résumé

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
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.

Identifiants

pubmed: 37376768
doi: 10.1111/resp.14543
doi:

Substances chimiques

Autoantibodies 0
Filaggrin Proteins 0
Tenascin 0
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid 77521-29-0
Peptides, Cyclic 0
Peptides 0
Fibrinogen 9001-32-5

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

925-933

Informations de copyright

© 2023 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.

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Auteurs

Dimitrios Kalafatis (D)

Respiratory Medicine Unit, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.

Vijay Joshua (V)

Division of Rheumatology, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.

Monika Hansson (M)

Division of Rheumatology, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.

Linda Mathsson-Alm (L)

Thermo Fisher Scientific, Uppsala, Sweden.

Aase Hensvold (A)

Division of Rheumatology, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Center for Rheumatology, Academic Specialist Center, Stockholm Health Region, Stockholm, Sweden.

Magnus Sköld (M)

Respiratory Medicine Unit, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden.

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