Imbalances in circulating lymphocyte subsets in Hu antibody associated paraneoplastic neurological syndromes.
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.
de Beukelaar
J W
JW
Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Sillevis Smitt
P A
PA
Hop
W C
WC
Kraan
J
J
Hooijkaas
H
H
Verjans
G M G M
GM
Gratama
J W
JW
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
D001323:Autoantibodies; D051959:ELAV Proteins