Evidence of a Sjögren's disease-like phenotype following COVID-19.

Autor:	Shen Y; Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA., Voigt A; Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA., Goranova L; Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA., Abed M; Salivary Disorder Unit, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland., Kleiner DE; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland., Maldonado JO; Salivary Disorder Unit, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland.; AAV Biology Section, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland, USA., Beach M; Salivary Disorder Unit, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland., Pelayo E; Salivary Disorder Unit, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland., Chiorini JA; AAV Biology Section, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland, USA., Craft WF; Department of Comparative, Diagnostic, and Population Medicine, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA., Ostrov DA; Department of Pathology, Immunology & Laboratory Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA., Ramiya V; LifeSouth Community Blood Centers, Gainesville Fl., Sukumaran S; Valley Children's Hospital, Madera, California., Tuanyok A; Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA., Warner BM; Salivary Disorder Unit, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland., Nguyen CQ; Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA.; Department of Oral Biology, College of Dentistry.; Center of Orphaned Autoimmune Diseases, University of Florida, Gainesville, Florida, USA.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2022 Oct 21. Date of Electronic Publication: 2022 Oct 21.
DOI:	10.1101/2022.10.20.22281265
Abstrakt:	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 for 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 monoclonal antibodies produced in recovered patients can both 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. Key Messages: What is already known about this subject?SAR-CoV-2 has a tropism for the salivary glands. However, whether the virus can induce clinical phenotypes of Sjögren's disease is unknown.What does this study add?Mice infected with SAR-CoV-2 showed loss of secretory function, elevated autoantibodies, and lymphocyte infiltration in glands.COVID-19 patients showed an increase in autoantibodies. Monoclonal antibodies produced in recovered patients can block ACE2/spike interaction and recognize nuclear antigens.Minor salivary gland biopsies of some convalescent subjects showed focal lymphocytic infiltrates with focus scores.How might this impact on clinical practice or future developments?Our data provide strong evidence for the role of SARS-CoV-2 in inducing Sjögren's disease-like phenotypes.Our work has implications for how patients will be diagnosed and treated effectively.
Databáze:	MEDLINE
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