2. Academic Validation
  3. Evidence of a Sjögren's disease-like phenotype following COVID-19 in mice and human

Evidence of a Sjögren's disease-like phenotype following COVID-19 in mice and human

  • JCI Insight. 2023 Sep 7;e166540. doi: 10.1172/jci.insight.166540.
Yiran Shen 1,  Alexandria Voigt 1,  Laura Goranova 1,  Mehdi A Abed 2,  David E Kleiner 3,  Jose O Maldonado 2,  Margaret Beach 2,  Eileen Pelayo 2,  John A Chiorini 4,  William F Craft 5,  David A Ostrov 6,  Vijay Ramiya 7,  Sukesh Sukumaran 8,  Ashley N Brown 9,  Kaley C Hanrahan 9,  Apichai Tuanyok 1,  Blake M Warner 2,  Cuong Q Nguyen 1
Affiliations

Affiliations

  • 1 Department of Infectious Diseases and Immunology, The University of Florida, Gainesville, United States of America.
  • 2 Salivary Disorder Unit, National Institute of Dental and Craniofacial Research, Bethesda, United States of America.
  • 3 Laboratory of Pathology, NCI/NIH, Bethesda, United States of America.
  • 4 Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, Bethesda, United States of America.
  • 5 Department of Comparative, Diagnostic & Population Medicine, The University of Florida, Gainesville, United States of America.
  • 6 Department of Pathology, Immunology and Laboratory Medicine, The University of Florida, Gainesville, United States of America.
  • 7 Immunology, LifeSouth Community Blood Centers, Gainesville, United States of America.
  • 8 Rheumatology, Valley Children's Hospital, Madera, United States of America.
  • 9 Department of Medicine, College of Medicine University of Florida, Orlando, United States of America.
PMID: 37676726 DOI: 10.1172/jci.insight.166540
Abstract

Objectives: Sjögren's Disease (SjD) is a chronic and systemic autoimmune disease characterized by lymphocytic infiltration and the development of dry eyes and dry mouth resulting from the secretory dysfunction of the exocrine glands. SARS-CoV-2 may trigger the development or progression of autoimmune diseases, as evidenced by increased autoantibodies in patients and the presentation of cardinal symptoms of SjD. The objective of the study was to determine whether SARS-CoV-2 induces the signature clinical symptoms of SjD.

Methods: The ACE2-transgenic mice were infected with SARS-CoV-2; SjD profiling was conducted. COVID-19 patients' sera were examined to detect the presence of autoantibodies. Clinical evaluations of convalescent COVID-19 subjects, including minor salivary gland (MSG) biopsies, were collected. Lastly, monoclonal Antibodies generated from single B cells of patients were interrogated for ACE2/spike inhibition and nuclear antigens.

Results: Mice infected with the virus showed a decreased saliva flow rate, elevated antinuclear Antibodies (ANAs) with anti-SSB/La, and lymphocyte infiltration in the lacrimal and salivary glands. Sera of COVID-19 patients showed an increase in ANA, anti-SSA/Ro52, and anti-SSB/La. The male patients showed elevated levels of anti-SSA/Ro52 compared to female patients, and female patients had more diverse ANA patterns. Minor salivary gland biopsies of convalescent COVID-19 subjects showed focal lymphocytic infiltrates in four of six subjects, and 2 of 6 subjects had focus scores >2. Lastly, we found that monoclonal Antibodies produced in recovered patients can block ACE2/spike interaction and recognize nuclear antigens.

Conclusion: Overall, our study shows a direct association between SARS-CoV-2 and SjD. Hallmark features of SjD salivary glands were histologically indistinguishable from convalescent COVID-19 subjects.The results potentially implicate that SARS-CoV-2 could be an environmental trigger for SjD.

Keywords

Autoimmunity; COVID-19; Rheumatology.

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