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Evidence of Site-Specific Mucosal Autoantibody Secretion in Rheumatoid Arthritis
Leiden Univ, Netherlands.
Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0003-4492-9172
Leiden Univ, Netherlands.
Reade & Amsterdam Univ, Netherlands.
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2025 (English)In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 77, no 3, p. 272-282Article in journal (Refereed) Published
Abstract [en]

ObjectiveAnti-citrullinated protein antibodies (ACPA) have been detected in sputum and saliva, indicating that anti-modified protein antibodies (AMPA) can be produced at mucosal sites in patients with rheumatoid arthritis (RA). However, the body's largest mucosal compartment, the gut, has not yet been examined. We therefore investigated the presence of several AMPA (ACPA, anti-carbamylated protein antibodies [anti-CarP], and anti-acetylated protein antibodies [AAPA]) at different mucosal sites, including the intestinal tract.MethodsPaired fecal/ileal wash, saliva, and serum samples of patients with RA and healthy volunteers were collected in two independent cohorts. Data involving feces were replicated in a third cohort. In these secretions, AMPA were analyzed using in-house enzyme-linked immunosorbent assay with unmodified peptides as control. In fecal samples, total IgA and anti-Escherichia coli IgA were measured.ResultsACPA, anti-CarP, and AAPA IgA were measurable in saliva of seropositive patients with RA (prevalence 9%-40%). No AMPA could be detected in feces. IgA was present because total IgA and anti-E. coli IgA were detectable in feces of ACPA-positive patients with RA and healthy donors. Results were confirmed in another cohort using colonoscopically collected ileal wash samples.ConclusionOur study shows the presence of ACPA, anti-CarP, and AAPA IgA in saliva of ACPA-seropositive patients with RA. However, no AMPA could be detected in feces/ileal wash samples of these patients, although our assays were able to measure other antigen-specific antibodies. These data suggest that mucosal autoantibody secretion may occur in the oral mucosa of patients with RA, whereas no evidence could be found for this process in the lower gastrointestinal tract.

Place, publisher, year, edition, pages
WILEY , 2025. Vol. 77, no 3, p. 272-282
National Category
Immunology in the Medical Area
Identifiers
URN: urn:nbn:se:liu:diva-210156DOI: 10.1002/art.43036ISI: 001357846800001PubMedID: 39420623Scopus ID: 2-s2.0-85209657651OAI: oai:DiVA.org:liu-210156DiVA, id: diva2:1917613
Note

Funding Agencies|Center for Clinical Research Dalarna

Available from: 2024-12-03 Created: 2024-12-03 Last updated: 2025-05-15

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Martinsson, KlaraKastbom, AlfSvärd, Anna
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Division of Inflammation and InfectionFaculty of Medicine and Health SciencesDepartment of Rheumatology
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