Dr. subacute sensory neuronopathy; VGCC, voltage-gated calcium channel == Shows == SOX2 antibodies only seen in small-cell lung malignancy (SCLC), not additional tumours 61% of individuals with Lambert-Eaton syndrome and SCLC have SOX2 antibodies. Individuals with paraneoplastic disorders only have SOX2 antibodies if SCLC is present. == 1. Intro == Paraneoplastic neurological disorders (PNDs) are a varied group of conditions in which distant tumour effects are thought to underlie the neurological demonstration. These effects are generally thought to be due to an immune-mediated process with cell-mediated and humoral parts. Inside a Europe-wide review, small-cell lung malignancy (SCLC) was the commonest connected tumour Azelastine HCl (Allergodil) in individuals with PNDs, (present in Rabbit Polyclonal to GPR137C over a third of cases), with non-small-cell lung malignancy, thymoma, lymphoma, ovarian and breast cancer found in a further 37% (Giometto et al., 2010). Many PNDs are associated with specific onconeural antibodies against intracellular antigens (Hu, Yo, Ri, CV2 (CRMP5), amphiphysin, Ma2), but there is considerable diversity such that no single antibody is associated with only one type of neurological presentation or underlying tumour (Pittock et al., 2004). For example, anti-Hu antibodies are found in patients presenting with a range of PNDs such as subacute sensory neuronopathy (SSN), limbic encephalitis (LE), paraneoplastic cerebellar degeneration (PCD), but also in patients with LEMS where the presence of Hu antibodies may be a marker of an underlying small-cell lung tumour (Titulaer et al., 2009). In addition, although patients with particular paraneoplastic neurological phenotypes often develop specific tumours (e.g. SCLC found in over 90% of paraneoplastic LEMS (Titulaer et al., 2011a) and ovarian teratoma in over 90% of patients with anti-NMDA-R encephalitis (Titulaer et al., 2013)), this is not always the case and some PND presentations can be associated with a number of different cancers (e.g. LE seen with tumours of the lung, testis, and breast, and also with Hodgkin’s lymphoma, teratoma, or thymoma) (Gozzard and Maddison, 2010). Antibodies to Azelastine HCl (Allergodil) certain antigens have been found to be useful markers of SCLC, most notably SOXB1 group antigens (SOX1, SOX2, SOX3), Sry-like high mobility group box proteins that are expressed in neuronal precursor cells and adult human cerebellum (Alcock et al., 2009). In the context of PNDs, a study of 86 patients with LEMS found antibodies to SOX proteins in 67% of 43 LEMS patients with an underlying SCLC, but only in 4.6% (2/43) of non-tumour LEMS patients (Titulaer et al., Azelastine HCl (Allergodil) 2009). In patients with PCD and SCLC, SOX1 antibodies were detected Azelastine HCl (Allergodil) in 80% of patients with coexistent LEMS, but only 38% of patients with real PCD (Sabater et al., 2013). SOX1 antibodies were found less frequently in patients with neuropathies (5/32, 16%), most often with associated SCLC and anti-Hu antibodies, although a similar number (4/22, 18%) experienced no underlying tumour (Tschernatsch et al., 2010). Recently, in a larger study of patients with additional neurological presentations, SOX1 antibodies were found in 2/247 (0.8%) patients with multiple sclerosis, 2/185 (1.1%) with neuropathy of unknown cause and 11/837 (1.3%) with suspected PNDs, most of whom had no underlying tumour, and none with SCLC (Berger et al., 2016). Prospective studies in SCLC patients have indicated that the presence of SOX2 antibody on its own is not related to a distinct real neurological phenotype, suggesting that SOX antibodies may be of most use in predicting the presence of an underlying SCLC with high specificity (Maddison et al., 2010;Chapman et al., 2011). As a number of patients may also present with neurological clinical features identical to classical PNDs such as LE or cerebellar ataxia, without an underlying tumour, we therefore aimed to establish firstly if SOX antibodies could be used to distinguish between paraneoplastic and non-paraneoplastic presentations in patients with a range of PNDs and neurological mimics, and second of all whether raised levels of SOX antibodies were present in a number of other common tumour types seen in PNDs, such as thymoma, teratoma, breast or ovarian malignancy. == 2. Methods == == 2.1. Patients == Sera were obtained from a number of patient groups (Table 1). == Table 1..