title: Imbalances in circulating lymphocyte subsets in Hu antibody associated paraneoplastic neurological syndromes.
abstract: In paraneoplastic neurological syndromes (PNS) associated with small cell lung cancer (SCLC) and Hu antibodies, neuron-specific Hu antigens expressed by the tumour hypothetically trigger an immune response that cross-reacts with Hu antigens in the nervous system, resulting in tumour suppression and neuronal damage. To gain more insight into the hypothesized cell-mediated immune pathogenesis of these syndromes, we analysed the circulating lymphocyte subsets in untreated patients with SCLC, PNS and Hu antibodies (n = 18), SCLC without PNS (n = 19) and controls (n = 29) using flow cytometry. SCLC patients with PNS had a variety of imbalances within their circulating lymphocyte subsets as compared with SCLC patients without PNS and healthy controls: (i) a lymphopenia of the major subsets (i.e. B, CD4+ and CD8+ T lymphocytes); (ii) increased proportions of activated CD4+ and CD8+ T cells; (iii) reduced numbers of terminally differentiated effector CD8+ T cells and cells with a cytotoxic T-cell phenotype (CD56+ and CD57+). Although indirect, our data provide further support for the involvement of T cells in the pathogenesis of Hu antibody associated PNS.
authors.affiliation: Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: de Beukelaar
authors.forename: P A
authors.initials: PA
authors.lastname: Sillevis Smitt
authors.forename: W C
authors.initials: WC
authors.lastname: Hop
authors.forename: J
authors.initials: J
authors.lastname: Kraan
authors.forename: H
authors.initials: H
authors.lastname: Hooijkaas
authors.forename: G M G M
authors.initials: GM
authors.lastname: Verjans
authors.forename: J W
authors.initials: JW
authors.lastname: Gratama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D051959:ELAV Proteins / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020361:Paraneoplastic Syndromes, Nervous System / Q000097:blood* / Q000276:immunology* / Q000503:physiopathology; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D001323:Autoantibodies; D051959:ELAV Proteins