Systems serology identifies FcR-related autoantibody signatures and functions for Sjögren’s syndrome

Sjögren's Syndrome (SjS) has historically been associated with classical anti-Ro60/SSA, Ro52/SSA and La/SSB, however they are lacking in one third of the patients, which induces delays in diagnosis, and their disease-contributing role is debated. Here we have applied a SjS-tailored Systems Serology approach to a cohort of 58 SjS and 16 non-SjS sicca syndrome patients, and 40 healthy individuals, involving a multiplex assay measuring antibody isotype, subclass, Fc Receptor and complement engagement to 14 SjS-related autoantigens, an antibody-glycosylation profiling assay and a phagocytosis cell-based assay. Via a machine learning approach, we have identified unique autoantibody signatures, including classical and non-classical autoantigens-related features especially involving autoantigen-specific Fc Receptor binding, with apparent functional consequences. These findings provide interesting insights into the autoantibody responses in SjS, possibly paving the way for improved diagnostics, especially in difficult-to-diagnose patients (e.g., seronegative SjS and non-SjS sicca syndrome patients), and novel therapeutic options targeting autoantibody-specific Fc/Fc Receptor-related effector functions.

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Publication Details

Journal
EMBO Molecular Medicine
Published
2026-06-17
DOI
https://doi.org/10.1038/s44321-026-00458-w
Primary Topic
Salivary Gland Disorders and Functions
Type
article
Field-Weighted Citation Impact
0.00

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article

Systems serology identifies FcR-related autoantibody signatures and functions for Sjögren’s syndrome

Quitterie Reynaud, Martin Killian, I. Durieu, Anne‐Emmanuelle Berger et al.
EMBO Molecular Medicine
Salivary Gland Disorders and Functions
article

Systems serology identifies FcR-related autoantibody signatures and functions for Sjögren’s syndrome

Quitterie Reynaud, Martin Killian, I. Durieu, Anne‐Emmanuelle Berger, Suzanne K. Shoffner, Héloïse Munoz-Pons, Ebene R. Haycroft, Alexis Bocquet, Baptiste Gramont, Hubert Marotte, Kelly B. Arnold, Pascal cathebras, Stéphane Paul, Édouard Ollier, P. Sève, Stephen John Kent, Yvan Jamilloux, F. Schein, Alice Haccourt, Isabelle Guichard, Bruce D. Wines, Timon Damelang, Blandine Chanut, Fabienne Jospin, Samantha K. Davis, Amy W. Chung, A Servettaz, Jean-Baptiste Gaultier, Lucile Grange, Laurence Bouillet, Marc Ruivard, Kevin John Selva, Kade E Wong, Rémy Harlé, Jean-Christophe Lega, P Mark Hogarth
article en

Abstract

Sjögren's Syndrome (SjS) has historically been associated with classical anti-Ro60/SSA, Ro52/SSA and La/SSB, however they are lacking in one third of the patients, which induces delays in diagnosis, and their disease-contributing role is debated. Here we have applied a SjS-tailored Systems Serology approach to a cohort of 58 SjS and 16 non-SjS sicca syndrome patients, and 40 healthy individuals, involving a multiplex assay measuring antibody isotype, subclass, Fc Receptor and complement engagement to 14 SjS-related autoantigens, an antibody-glycosylation profiling assay and a phagocytosis cell-based assay. Via a machine learning approach, we have identified unique autoantibody signatures, including classical and non-classical autoantigens-related features especially involving autoantigen-specific Fc Receptor binding, with apparent functional consequences. These findings provide interesting insights into the autoantibody responses in SjS, possibly paving the way for improved diagnostics, especially in difficult-to-diagnose patients (e.g., seronegative SjS and non-SjS sicca syndrome patients), and novel therapeutic options targeting autoantibody-specific Fc/Fc Receptor-related effector functions.

EMBO Molecular Medicine
Université Claude Bernard Lyon 1 (FR), Institut polytechnique de Grenoble (FR), Centre National de la Recherche Scientifique (FR), Burnet Institute (AU), Inserm (FR), The University of Melbourne (AU), University of Michigan (US), Centre Hospitalier Universitaire de Grenoble (FR), Hôpital de la Croix-Rousse (FR), Melbourne Sexual Health Centre (AU), Clinical Investigation Center Plurithematic Tours (FR), Hospices Civils de Lyon (FR), Peter Doherty Institute (AU), Centre Hospitalier Universitaire de Reims (FR), Hôpital Lyon Sud (FR), Health Services and Performance Research Laboratory (FR), Centre Hospitalier Universitaire de Clermont-Ferrand (FR), Laboratoire de Biométrie et Biologie Evolutive (FR), Centre Hospitalier Universitaire de Saint-Étienne (FR), Monash University (AU), Université Jean Monnet (FR), Université Grenoble Alpes (FR), Université de Reims Champagne-Ardenne (FR)
Groupe Pasteur Mutualité, Ministère de la Santé, Servier, Institut Servier, National Health and Medical Research Council
Openalex Percentile: Top 8%
Salivary Gland Disorders and Functions
DOIOpen Access PDFOpenAlex
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