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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月17日

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

摘要

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.