title: B cell receptor signaling-based index as a biomarker for the loss of peripheral immune tolerance in autoreactive B cells in rheumatoid arthritis.
abstract: This study examines the loss of peripherally induced B cell immune tolerance in Rheumatoid arthritis (RA) and establishes a novel signaling-based measure of activation in a subset of autoreactive B cells--the Induced tolerance status index (ITSI). Naturally occurring naïve autoreactive B cells can escape the "classical" tolerogenic mechanisms of clonal deletion and receptor editing, but remain peripherally tolerized through B cell receptor (BCR) signaling inhibition (postdevelopmental "receptor tuning" or anergy). ITSI is a statistical index that numerically determines the level of homology between activation patterns of BCR signaling intermediaries in B cells that are either tolerized or activated by auto antigen exposure, and thus quantifies the level of peripheral immune tolerance. The index is based on the logistic regression analysis of phosphorylation levels in a panel of BCR signaling proteins. Our results demonstrate a new approach to identifying autoreactive B cells based on their BCR signaling features.
authors: Division of Rheumatology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors: Taras
authors: T
authors: Lyubchenko
authors: Department of Biostatistics and Informatics, University of Colorado School of Public Health, Aurora, Colorado, United States of America.
authors: Gary O
authors: GO
authors: Zerbe
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001324:Autoantigens / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D017635:Clonal Anergy / Q000235:genetics; D017637:Clonal Deletion / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D016015:Logistic Models; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D061166:Peripheral Tolerance / Q000235:genetics*; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000276:immunology
chemical_list: D001324:Autoantigens; D015415:Biomarkers; D011947:Receptors, Antigen, B-Cell