Abstract
Sjögren’s Disease (SjD) is a systemic autoimmune disease characterized by lymphocytic inflammation of the lacrimal and salivary glands (SG), dry eyes and mouth, and systemic symptoms. SARS-CoV-2 may trigger the development or progression of autoimmune diseases. To test this, we used a mouse model of SARS-CoV-2 infection and convalescent patients’ blood and SG in order to understand the development of SjD-like autoimmunity after infection. First, SARS-CoV-2–infected human angiotensin-converting enzyme 2 (ACE2) transgenic mice exhibited decreased salivation, elevated antinuclear antibodies (ANA), and lymphocytic infiltration in the lacrimal and SG. The sera from patients with COVID-19 sera showed increased ANA (i.e., anti-SSA [Sjögren’s-syndrome-related antigen A]/anti-Ro52 and anti-SSB [SS-antigen B]/anti-La). Male patients showed elevated anti-SSA compared with female patients, and female patients exhibited diverse ANA patterns. SG biopsies from convalescent COVID-19 patients were microscopically similar to SjD SG with focal lymphocytic infiltrates in 4 of 6 patients and 2 of 6 patients exhibiting focus scores of at least 2. Lastly, monoclonal antibodies produced in recovered patients blocked ACE2/spike interaction and cross-reacted with nuclear antigens. Our study shows a direct association between SARS-CoV-2 and SjD. Hallmark features of SjD-affected SGs were histologically indistinguishable from convalescent COVID-19 patients. The results implicate that SARS-CoV-2 could be an environmental trigger for SjD.
Authors
Yiran Shen, Alexandria Voigt, Laura Goranova, Mehdi Abed, David E. Kleiner, Jose O. Maldonado, Margaret Beach, Eileen Pelayo, John A. Chiorini, William F. Craft, David A. Ostrov, Vijay Ramiya, Sukesh Sukumaran, Ashley N. Brown, Kaley C. Hanrahan, Apichai Tuanyok, Blake M. Warner, Cuong Q. Nguyen
Immunophenotyping of SGs of convalescent COVID-19 patients
