Microbiota-specific serum IgG links gut and joints through immune–endothelial crosstalk in arthritis

Schmid E, Otterbein N, Ariyeloye S, Danzer H, Frech M, Naschberger E, Munoz Becerra M, Sarter K, Schett G, Kastbom A, Svärd A, Wielockx B, Zaiss M (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Frontiers in Microbiology Frontiers Media

Book Volume: 17

Article Number: 1821367

DOI: 10.3389/fmicb.2026.1821367

Abstract

Rheumatoid arthritis (RA) pathogenesis involves early gut immune alterations that precede clinical onset and systemic bone involvement. Using mouse and human imaging mass cytometry (IMC) and tissue sequencing, this study shows that intestinal endothelial and immune changes emerge before or coincide with arthritis symptom development. In the collagen-induced arthritis (CIA) model, intestinal vascular permeability and endothelial gene activation promoting leukocyte trafficking appeared prior to synovial inflammation. Spatial mapping of murine and human ileal tissues predicted enhanced epithelial–immune interactions and lymphoid activation, suggesting mucosal immune priming before joint pathology. Both gut-selective α4β7 integrin blockade with vedolizumab and endothelial barrier enhancement by imatinib significantly reduced arthritis severity in CIA mice. After clinical onset, microbiota-specific IgG responses expanded to recognize rare gut bacteria, reflecting increased microbial exposure. Bone marrow endothelium exhibited interferon-I–driven inflammation and vascular activation, indicating tissue-specific endothelial dysfunction. Microbiota-reactive IgG increased during CIA—likely a response to increased bacterial antigen exposure and immune cell activation. Integrating mouse and human data, these findings define a mechanistic framework where endothelial barrier impairment, microbial translocation, and systemic endothelial activation initiate RA autoimmunity, revealing endothelial and mucosal pathways as targets for early intervention.

Authors with CRIS profile

Eva Schmid Department of Medicine 3 – Rheumatology and Immunology Nadine Otterbein Department of Medicine 3 – Rheumatology and Immunology Michael Frech Department of Medicine 3 – Rheumatology and Immunology Elisabeth Naschberger Medizinische Fakultät Marco Munoz Becerra Department of Medicine 3 – Rheumatology and Immunology Kerstin Sarter-Zaiss Department of Medicine 3 – Rheumatology and Immunology Georg Schett Lehrstuhl für Innere Medizin III Mario Zaiss Professur für Immuntoleranz und Autoimmunität

Involved external institutions

Technische Universität Dresden DE Germany (DE) Linköpings universitet / Linköping University SE Sweden (SE)

How to cite

APA:

Schmid, E., Otterbein, N., Ariyeloye, S., Danzer, H., Frech, M., Naschberger, E.,... Zaiss, M. (2026). Microbiota-specific serum IgG links gut and joints through immune–endothelial crosstalk in arthritis. Frontiers in Microbiology, 17. https://doi.org/10.3389/fmicb.2026.1821367

MLA:

Schmid, Eva, et al. "Microbiota-specific serum IgG links gut and joints through immune–endothelial crosstalk in arthritis." Frontiers in Microbiology 17 (2026).

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