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BRIEF RESEARCH REPORT article

Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1516330
This article is part of the Research Topic Novel Biomarkers for Early Diagnosis, involved in Autoimmune and Autoinflammatory Diseases View all 4 articles

Serum and Tear Autoantibodies from NOD and NOR Mice as Potential Diagnostic Indicators of Local and Systemic Inflammation in Sjögren's Disease

Provisionally accepted
Shruti Singh Kakan Shruti Singh Kakan 1Sara Abdelhamid Sara Abdelhamid 1Yaping Ju Yaping Ju 1Andrew Mackay Andrew Mackay 2Maria C Edman-Woolcott Maria C Edman-Woolcott 1Indu Raman Indu Raman 3Chengsong Zhu Chengsong Zhu 3Prithvi Raj Prithvi Raj 3Sarah F Hamm-Alvarez Sarah F Hamm-Alvarez 1*
  • 1 Department of Ophthalmology, Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, United States
  • 2 Department of Pharmacology & Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences,, University of Southern California, Los Angeles, California, United States
  • 3 Department of Immunology, Microarray and Immune Phenotyping Core Facility, Southwestern Medical Center, The University of Texas at Dallas, Richardson, Texas, United States

The final, formatted version of the article will be published soon.

    Sjögren's Disease (SjD) is an autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands (LG). The LG produces the protein-rich aqueous component of tears, and SjD-associated autoimmune dacryoadenitis (AD) may thus alter tear autoantibody composition. The presence of tertiary lymphoid structures (TLS) in LG from two murine models of SjD-associated AD, male non-obese diabetic (NOD) and male non-obese insulitis resistant (NOR) mice, were evaluated using immunofluorescence. IgG and IgA reactivity in serum and tears from these models were probed in three studies against a panel of 80-120 autoantigens using autoantibody microarrays relative to serum and tears from healthy male BALB/c mice. Sources of Ig in tears were investigated using scRNA-Seq of the LG (GSE132420). Data were analyzed by R package Limma and Seurat. Analysis of immunofluorescence in LG sections from both SjD models showed TLS. Only one autoantibody was significantly elevated in tears and serum in both SjD models across all studies. Three autoantibodies were significantly elevated in serum but not in tears in both SjD models across all studies. Conversely, six IgG and thirteen IgA autoantibodies (6 sharing the same autoantigen) were significantly elevated in tears but not serum in both SjD models. Igha and Ighg2b expressing cells were identified in the plasma cell cluster of NOD.H2b LG. NOD and NOR mice with SjD-associated AD have distinct autoantibody profiles in tears and serum. Tear IgA isotype autoantibodies showed a greater diversity than tear IgG autoantibodies. TLS observed in LG are a likely source of the tear autoantibodies.

    Keywords: Sjögren's disease, autoimmune disease, IgA autoantibodies, IgG autoantibodies, Tear film, Serum

    Received: 24 Oct 2024; Accepted: 30 Dec 2024.

    Copyright: © 2024 Singh Kakan, Abdelhamid, Ju, Mackay, Edman-Woolcott, Raman, Zhu, Raj and Hamm-Alvarez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Sarah F Hamm-Alvarez, Department of Ophthalmology, Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.