PNS may affect any part of the nervous system and muscles. Immunoresponses to cancer, which cross-react with self-antigens in the nervous system or muscle lead to production of onconeuronal antibodies detection [16], [17]. Despite the efforts to elucidate the effects of such antibodies on neurons, only a few onconeuronal http://www.selleckchem.com/products/CHIR-258.html antibodies have been identified as primary effectors of neurological symptoms. PNS is uncommon and defined by an acute or sub-acute neurological syndrome associated with a cancer. Examples of PNS are sub-acute cerebellar ataxia, limbic encephalomyelitis, Lambert-Eaton myasthenic syndrome, dermatopolymyositis and intestinal pseudo- obstruction [15]. The symptoms of PNS often appear before the diagnosis of malignant cancer and probable cases of PNS may suggest early antitumor therapy and immunotherapy to prevent progressive neuronal death.

Symptoms can be also caused by neuroendocrine cells that are present in the GI tract and in the lung [2]. However, understanding whether the antibodies are associated with specific neurological symptoms or are only marker of anticancer immune reaction is difficult [16]. The functions of the proteins encoded by PNMA genes are not clear. However, MOAP1/PNMA4 was identified as a Bax-associating protein inducing apoptosis in mammalian cells. The significant homology of MOAP1/PNMA4 and the other PNMA proteins suggested a potential role in apoptosis for PNMA proteins [18], [19]. Antitumor immune responses to neuronal antigens expressed by tumor cells may lead to detectable levels of antibodies in serum and plasma [14], [15], [16].

Voltz et al. identified anti-Ma2 antibodies in patients suffering from testicular cancer and paraneoplastic limbic or brain-stem encephalitis or both [20]. The antibodies are often present in sera from patients suffering from neurological PNS [15], [21], [22]. Scientific evidence has shown that anti-Ma2 positive sera sometimes are associated with tumor diagnosis [15], [16], [23], [24]. The finding that Ma2 is expressed in primary SI-NETs and metastases [13] prompted us to screen whether Ma2 autoantibodies are detectable in blood of NET patients to establish potential novel biomarkers and to evaluate their clinical implications in tumor diagnosis and prognosis. In this study, we set up a novel indirect enzyme-linked immunosorbent assay (ELISA) to detect Ma2 autoantibodies in blood samples of 124 SI-NET patients at different stages of disease.

We also extended the evaluation to lung carcinoid patients’ blood to verify that our assay is able to detect the presence of Ma2 autoantibodies in different neuroendocrine tumors. SI-NETs and lung carcinoids originate from cells, which synthesize and secrete biologically active compounds that are able to Cilengitide produce either humoral PNS or less commonly neurological PNS.