Paraneoplastic Neurological Syndromes associated with anti-Hu antibodies: are T lymphocytes involved or not?

In paraneoplastic neurological syndromes (PNS), ectopic expression of onconeural antigens by the tumor triggers an immune response that not only reacts with the tumor but also with the same antigens expressed in the nervous system. This immune response inhibits tumor growth. However, the price of tumor control is high, as PNS are devastating neurological syndromes leaving most of the patients severely disabled within a few months. One of the most frequently involved tumors is small cell lung cancer (SCLC), and approximately 50% of patients with PNS and SCLC have high-titer antibodies against the onconeural Hu-antigens (anti-Hu). Previous studies have clearly demonstrated that anti-Hu antibodies do not play a pathogenic role in Hu-PNS and tumor control, but rather are a useful diagnostic marker. Therefore, a role for the cellular immune system in the pathogenesis of PNS is hypothesized. In this thesis the role of T cells in PNS was investigated by studying CSF and blood of Hu-PNS patients. This role of T cells was confirmed by (i) 4-fold higher T lymphocyte numbers in CSF of Hu-PNS patients compared to controls; (ii) association of Hu-PNS with HLA-DQ2 and HLA-DR3; and (iii) neurological improvement or stabilization upon treatment with hCG. However, the presence of HuD-specific CD8+ T cells in CSF could not be demonstrated. Therefore, more research is required to either confirm or reject a role for T lymphocytes in Hu-PNS.

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