104 SLE autoantibodies to casein kinase II: potential mediators of immunopathology. (14th December 2022)

• Record Type: Journal Article
• Authors: Shu, Daniel H; Merrill, Joan T; Cohen, Philip L
• Is Part Of: Lupus science & medicine. Volume 9(2022)Supplement 3
• Page Start: A6
• Page End: A7
• Publication Date: 2022-12-14
• Subjects: Systemic lupus erythematosus -- Periodicals; 616.772005
• DOI: 10.1136/lupus-2022-lupus21century.4
• Languages: English
• ISSNs: 2398-8851

Abstract

Abstract : Background: Casein kinase II (CSNK2) is a key regulator of cell activation, proliferation, and apoptosis. While primarily an intracellular molecule, it has recently been appreciated that CSNK2 is expressed on cell surfaces, where it functions as an ectoenzyme with broad regulatory activity. Its presence of cell surfaces raises the possibility that autoantibodies to CSNK2 might interfere with its function and mediate immunopathology. A role for CSNK2 autoantibodies was suggested 30 years ago in animal models. More recently, we have used protein array technology (Protoarray, Invitrogen Technologies) to investigate the full spectrum of SLE autoantibodies. A study of patient sera from three different cohorts (Philadelphia, Romania, and People's Republic of China) showed that autoantibodies to the alpha (catalytic) subunit of CSNK2 were among the top seventeen self specificities found in common among these diverse lupus sera. In the present study, we developed a formal ELISA to investigate autoantibodies to CSNK2 in two well studied collections of SLE sera. Methods: We developed an ELISA binding assay for CSNK2 autoantibodies. We inhibited the ELISA to show antigen specificity, and we performed Western blots to show that the lupus sera recognized recombinant antigen. We used the clinical information about both cohorts to look for clinical correlations with the presence of this autoantibody. Results: Using recombinant human alpha subunit of human CSNK2 (Lifespan Technologies), we developed an ELISA to test binding of lupus and control sera to CSNK2. We examined 114 SLE sera and age and sex matched controls from Philadelphia, and 99 paired lupus sera from Oklahoma City. We showed by Western blot that lupus sera bound to the same molecular weight recombinant CSNK2 as rabbit antisera to this protein. The presence of autoantibodies to CSNK2 correlated with overall SLEDAI and with new onset arthritis in the two groups. Other correlations were inconsistent. Conclusions: Most SLE autoantibodies are directed against intracellular (often intranuclear) antigens. The prevalence in SLE of autoantibodies to a key regulatory ectoenzyme is of interest and raises the possibility that such antibodies might play a role in pathogenesis. Antibodies to the CSNK2 catalytic subunit may interfere with its function in regulating cell growth, apoptosis, and activation. As the ectoenzyme is expressed on endothelial cells, lymphocytes, neutrophils, and monocyte-macrophages, there is the potential for broad effects on inflammation and immunity. The antibodies we have described deserve further investigation.