Imbalance in circulating T lymphocyte subsets contributes to Hu antibody-associated paraneoplastic neurological syndromes

Abstract

Paraneoplastic neurological syndromes (PNS) are associated with small cell lung cancer (SCLC) and Hu antibodies, which are considered to have an immune-mediated etiology. As a pathogenic role for Hu antibodies (Hu-Ab) in PNS could not be demonstrated, the cellular immune response against the Hu proteins has been further investigated. To delve deeper into the hypothesized cell-mediated immune pathogenesis of these syndromes, imbalances within circulating T lymphocyte subsets were investigated to determine their significance in Hu antibody-associated PNS. The circulating T lymphocyte subsets were analyzed in untreated patients with SCLC, PNS and Hu-Ab (n=10), SCLC without PNS (n=10) and healthy controls (n=12) using flow cytometry. Patients with PNS and SCLC, had a variety of changes within their circulating T lymphocyte subsets, which included; lymphopenia of the CD3+and CD4+ T cells, increased proportions of total activated T cells and activated CD4+ T cells, and reduced numbers of CD4+ and CD25+ regulatory T cells (Treg). These results suggest that the excessive activation of T cells and dysfunction of Treg contribute to Hu antibody-associated PNS.