title: Light chain-restricted autoantibodies in chronic idiopathic thrombocytopenic purpura, but no evidence for circulating clone B-lymphocytes.
abstract: In chronic idiopathic thrombocytopenic purpura (ITP) platelet destruction is caused by antibodies directed against platelet membrane glycoproteins (GP), and the predominant autoantigens are known to be GPIb/IX and GPIIb/IIIa. In a recent study we reported that these antibodies frequently had a restricted light chain phenotype, thereby supporting a clonal origin. Similar findings and the presence of clonal B-cell populations in immune thrombocytopenias have been reported by others. In the present study we further explored the hypothesis of clonal B-cell expansions in chronic ITP. Twenty patients with chronic ITP were investigated. Antibodies were detected with an ELISA (MAIPA) specific for GPIb/IX and GPIIb/IIIa; circulating clonal B lymphocytes were assessed by flow-cytometric (FACS) clonal-excess analysis and by analyzing Ig-gene rearrangements (CDR3) with the PCR technique. Nine patients displayed a GP-specific antibody restricted to either kappa or lambda phenotype. However, FACS analysis and Ig-gene rearrangement studies did not disclose any circulating clonal B-cell population. Considering the sensitivity of the FACs analysis and Ig-gene rearrangement for detection of clonal B-cell populations, the hypothesis of clonally derived autoantibodies in ITP is still valid. Most probably, the clonal B-cell expansion responsible for the production of autoantibodies in ITP, if present, is below the detection limit for the techniques employed.
authors.affiliation: Department of Medicine, Sahlgrenska Hospital, Göteborg, Sweden.
authors.forename: D
authors.initials: D
authors.lastname: Stockelberg
authors.forename: M
authors.initials: M
authors.lastname: Hou
authors.forename: S
authors.initials: S
authors.lastname: Jacobsson
authors.forename: J
authors.initials: J
authors.lastname: Kutti
authors.forename: H
authors.initials: H
authors.lastname: Wadenvik
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000276:immunology*; D016131:Lymphocyte Subsets; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D007147:Immunoglobulin Light Chains