SARS-CoV-2 spike aggravates lupus nephritis and lung fibrosis in systemic lupus erythematosus

• Published in: Lupus science & medicine Vol. 11; no. 2; p. e001104
• Main Authors: Lee, Yeon Su, Woo, Jin Seok, Jhun, JooYeon, Choi, Jeong Won, Lee, A Ram, Lee, Kun Hee, Choi, Haeyoun, Park, Sung-Hwan, Cho, Mi-La
• Format: Journal Article
• Language: English
• Published: England Lupus Foundation of America 30.09.2024; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: Angiotensin-Converting Enzyme 2 - genetics; Angiotensin-Converting Enzyme 2 - metabolism; Animals; Antibodies; Autoantibodies - blood; Autoimmune diseases; COVID-19; COVID-19 - complications; COVID-19 - immunology; COVID-19 vaccines; Cytokines; Disease; Disease Models, Animal; Female; Flow cytometry; Immunohistochemistry; Infections; Laboratories; Lupus; lupus erythematosus, systemic; Lupus Erythematosus, Systemic - complications; Lupus Erythematosus, Systemic - immunology; Lupus Nephritis; Lupus Nephritis - immunology; Lupus Nephritis - pathology; Medical research; Mice; Mice, Inbred BALB C; Mice, Inbred MRL lpr; Mice, Knockout; Original Research; Plasmids; Proteins; Pulmonary embolisms; pulmonary fibrosis; Pulmonary Fibrosis - etiology; Pulmonary Fibrosis - immunology; Pulmonary Fibrosis - pathology; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Software; Spike Glycoprotein, Coronavirus - immunology; Splenomegaly - etiology; Statistical analysis; Thrombosis; Urine; Viral infections; California; United States > US; Massachusetts; Japan; COVID-19; lupus erythematosus, systemic; lupus nephritis; pulmonary fibrosis
• ISSN: 2053-8790; 2053-8790
• DOI: 10.1136/lupus-2023-001104

ObjectiveCOVID-19 induces the development of autoimmune diseases, including SLE, which are characterised by inflammation, autoantibodies and thrombosis. However, the effects of COVID-19 on SLE remain unclear.MethodsWe investigated the effects of COVID-19 on SLE development and progression in three animal models. Plasmids encoding SARS-CoV-2 spike protein and ACE2 receptor were injected into R848-induced BALB/C lupus mice, R848-induced IL-1 receptor antagonist knockout (KO) lupus mice and MRL/lpr mice. Serum levels of albumin and autoantibodies, lymphocyte phenotypes and tissue histology were evaluated.ResultsIn R848-induced BALB/C lupus mice, the SARS-CoV-2 spike protein increased autoantibody and albumin levels compared with vehicle and mock treatments. These mice also exhibited splenomegaly, which was further exacerbated by the spike protein. Flow cytometric analysis revealed elevated T helper 1 cell counts, and histological analysis indicated increased levels of the fibrosis marker protein α-smooth muscle actin. In KO mice, the spike protein induced splenomegaly, severe kidney damage and pronounced lung fibrosis. In the MRL/lpr group, spike protein increased the serum levels of autoantibodies, albumin and the thrombosis marker chemokine (C-X-C motif) ligand 4.ConclusionCOVID-19 accelerated the development and progression of lupus by inducing autoantibody production, fibrosis and thrombosis.