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.