title: Treatment with TNFα blockers induces phenotypical and functional aberrations in peripheral B cells.
abstract: To dissect the mechanisms of anti-TNFα-induced autoimmunity we examined the phenotype and function of B cells from anti-TNFα-treated patients. Levels of Lyn, Syk, SHP-1, tyrosine 348 phospho-Syk (Y348-Syk) and tyrosine phosphorylated (P-Y) proteins were evaluated and B-cell-surface CD20, CD21 and CD5 were also assessed in 29 patients treated with TNF-α blockers. Following treatment, Lyn, but not Syk or SHP-1, significantly increased particularly in patients with spondyloarthropathies. Increased Lyn levels following treatment correlated with increased Lyn activity as evidenced by a 2.9-fold increase of Y348-Syk (a Lyn target). Peripheral B-cells from 56.3% of the patients displayed a tendency towards increased P-Y levels without any BCR-initiated activation during treatment. CD20, but not CD21, significantly increased in patients with rheumatoid arthritis. Circulating CD5+ B-cells were also significantly expanded during treatment. Our findings suggest that B cells in anti-TNFα-treated patients display functional and phenotypical aberrations that may enhance our understanding of TNF-α blocker-induced autoimmunity.
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, University of Patras Medical School, Patras, Greece.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Karampetsou
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Andonopoulos
authors.forename: Stamatis-Nick C
authors.initials: SN
authors.lastname: Liossis
mesh_terms: D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20 / Q000096:biosynthesis; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D018956:CD5 Antigens / Q000096:biosynthesis; D002469:Cell Separation; D000068800:Etanercept; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D010641:Phenotype; D010766:Phosphorylation; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000096:biosynthesis; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D017464:Receptors, Complement 3d / Q000096:biosynthesis; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D000072377:Syk Kinase; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D019061:src-Family Kinases / Q000096:biosynthesis
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20; D018501:Antirheumatic Agents; D018956:CD5 Antigens; D007074:Immunoglobulin G; D047908:Intracellular Signaling Peptides and Proteins; D017464:Receptors, Complement 3d; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D000068879:Adalimumab; D000068800:Etanercept