1/7. Paraneoplastic syndrome in the course of lung adenocarcinoma: morphological picture and immunohistochemical analysis of the inflammatory infiltrates and PECAM-1 expression.We examined sections of brain, spinal cord, spinal roots, and peripheral nerves from a patient with paraneoplastic syndrome in the course of lung adenocarcinoma. Morphological examination showed marked loss of myelin fibers in peripheral nerves, severe brain tissue edema, and paraneoplastic degeneration involving cerebrum and cerebellum with inflammatory components. Inflammatory infiltrates examined immunohistochemically using antibodies against antigens CD 3, CD 4, CD 8, and CD 20 turned out to be composed of cytotoxic T lymphocytes. The expression of platelet-endothelial cell adhesion molecule-1 (PECAM-1) in blood vessels was increased in comparison with control material, which may facilitate transendothelial lymphocyte migration triggering a cascade of biochemical and morphological reactions observed in paraneoplastic syndrome.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/7. Paraneoplastic brain stem encephalitis in a woman with anti-Ma2 antibody.A woman developed brain stem encephalopathy in association with serum anti-Ma2 antibodies and left upper lobe lung mass. T2 weighted MRI of the brain showed abnormalities involving the pons, left middle and superior cerebellar peduncles, and bilateral basal ganglia. Immunohistochemical analysis for serum antineuronal antibodies was confounded by the presence of a non-neuronal specific antinuclear antibody. Immunoblot studies showed the presence of anti-Ma2 antibodies. A premortem tissue diagnosis of the lung mass could not be established despite two CT guided needle biopsies, and the patient died as a result of rapid neurological deterioration. The necropsy showed that the lung lesion was an adenocarcinoma which expressed Ma2 immunoreactive protein. Neuropathological findings included prominent perivascular inflammatory infiltrates, glial nodules, and neuronophagia involving the brain stem, basal ganglia, hippocampus and the dentate nucleus of the cerebellum. Ma2 is an autoantigen previously identified in patients with germ cell tumours of the testis and paraneoplastic brain stem and limbic encephalitis. Our patient's clinical and immunopathological findings indicate that this disorder can affect women with lung adenocarcinoma, and that the encephalitic changes predominate in those regions of the brain known to express high concentrations of Ma proteins.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
3/7. ANNA-3 anti-neuronal nuclear antibody: marker of lung cancer-related autoimmunity.Two anti-neuronal nuclear antibodies (ANNA-1 and ANNA-2) are markers of paraneoplastic neurological autoimmunity related to small-cell carcinoma. ANNA-2 is also related to breast carcinoma. Here we define a third IgG specificity (ANNA-3), identified in 11 patients (10 adults) by immunofluorescence screening of sera from approximately 68,000 patients with suspected paraneoplastic neurological syndromes. ANNA-3 binds prominently to nuclei of cerebellar Purkinje neurons, not to cytoplasm, granular neurons, or enteric neurons, but distinctively to renal glomerular podocytes. Western blots revealed an approximately 170 kDa antigen, in cerebellum and small-cell carcinoma. IgG eluted from this protein reproduced Purkinje and podocyte nuclear staining. ANNA-2 in 8 of 32 cases bound to podocyte nuclei but not to the 170 kDa protein. Healthy subjects and control neurological and cancer patients lack ANNA-3. Neurological accompaniments, subacute and usually multifocal, included sensory/sensorimotor neuropathies, cerebellar ataxia, myelopathy, brain stem and limbic encephalopathy. All of 9 adults followed had an intrathoracic neoplasm, seven biopsied within 7 months (five small-cell lung carcinomas and two adenocarcinomas, one lung, one esophagus) and two imaged, one early, the other 3 years later. Thus, immunohistochemical and Western blot criteria can now identify six IgG markers of neurological autoimmunity related to small-cell carcinoma, their frequency being ANNA-1 > collapsin response-mediator protein-5 > amphiphysin > Purkinje cell cytoplasmic antibody-2 = ANNA-2 = ANNA-3.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
4/7. Quantification of circulating anti-Hu antibody in serial samples from patients with paraneoplastic neurological syndromes: possible correlation of antibody concentration and course of neurological symptoms.Serial samples, spanning an observation period of 4 to 10 years, from five patients with anti-Hu associated paraneoplastic neurological syndromes (PNS) were investigated with an enzyme linked immunosorbent assay (ELISA) employing recombinant HuD protein as antigen. In one patient the anti-Hu antibody concentration converted from negative to highly positive levels after the onset of neurological symptoms. These findings argue in favour of the idea that an autoimmune process, which is generated at the beginning of the neurological disease, causes the anti-Hu associated PNS. serum samples obtained shortly after the beginning of the PNS were available from two other patients. The anti-Hu antibody levels in these latter patients increased from modest to highly positive anti-Hu antibody in follow up samples. In two patients a clear decrease of the anti-HuD antibody concentration together with an improvement of paraneoplastic neurological symptoms after successful tumour treatment were seen. overall these data suggest that there might be a correlation between the anti-HuD antibody level and the clinical course of paraneoplastic neurological symptoms which supports further the hypothesis that an autoimmune process is responsible for the anti-Hu associated paraneoplastic neurological symptoms.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
5/7. Anti-Ri antibody positive opsoclonus-myoclonus in a male patient with breast carcinoma.A 65-year-old male patient developed truncal ataxia, opsoclonus and myoclonus. In the serum anti-Ri antibodies were found, which led to the detection of a small adenocarcinoma of the breast. Other prominent clinical features were an excessive startle response and behavioral disorders, such as anxiety and impatience. These features suggest an immune response against both Nova-1 and Nova-2 antigens throughout the central nervous system.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
6/7. BR serine/threonine kinase 2: a new autoantigen in paraneoplastic limbic encephalitis.We describe a new antigen, BR serine/threonine kinase 2 (BRSK2), identified by an antibody present in the serum of a patient with limbic encephalitis and small-cell lung cancer (SCLC). Patient's serum immunolabeled the neuronal cytoplasm and, less intense, the neuropil of rat brain but did not immunoreact with other rat tissues with the exception of testis. Immunoblots of rat brain homogenate identified several immunoreactive bands in the range of 88-82 kDa and a weaker broad band of 47-43 kDa. Probing a rat hippocampus expression library with the patient's serum resulted in the isolation of BR serine/threonine kinase 2 (BRSK2), a protein (also know as SAD1B kinase) preferentially expressed in the brain and testis and implicated in neuronal polarization as well as synaptic development. Eluted IgG from the BRSK2 clone gave a similar immunolabeling than the patient's serum by immunohistochemistry and immunoblot of rat brain and testis. BRSK2 antibodies reacted with two SCLC from patients without paraneoplastic neurological syndromes. No anti-BRSK2 antibodies were found in the serum of 50 patients with SCLC without PNS, 19 with limbic encephalitis without onconeural antibodies, 50 with anti-Hu antibodies and several paraneoplastic neurological syndromes, including 14 with limbic encephalitis, and 160 with a variety of non-paraneoplastic neurological syndromes. Our study suggests BRSK2 may be an autoantigen involved in the pathogenesis of SCLC-associated limbic encephalitis.- - - - - - - - - - ranking = 6keywords = antigen (Clic here for more details about this article) |
7/7. Post-streptococcal opsoclonus-myoclonus syndrome associated with anti-neuroleukin antibodies.BACKGROUND: adult opsoclonus-myoclonus (OM), a disorder of eye movements accompanied by myoclonus affecting the trunk, limbs, or head, is commonly associated with an underlying malignancy or precipitated by viral infection. methods: We present the first two reports of post-streptococcal OM associated with antibodies against a 56 kDa protein. Two young girls presented with opsoclonus and myoclonus following a febrile illness and pharyngitis. Protein purification techniques were employed. Amino acid sequences of human neuroleukin (NLK) and streptococcal proteins were compared using the protein-protein BLAST application. RESULTS: The antigen was identified as NLK (glucose-6-phosphate isomerase, GPI). GPI is present on the cell surface of streptococcus making the protein a candidate target for molecular mimicry. CONCLUSIONS: We have identified NLK as an antigenic target in two patients with post-streptococcal OM. The pathogenicity of the antibodies is uncertain. The potential role of anti-neuroleukin antibodies in the pathogenesis of OM is discussed. We propose that OM may represent a further syndrome in the growing spectrum of post-streptococcal neurological disorders. The role of streptococcus in OM and the frequency with which anti-NLK responses occur in both post-infectious and paraneoplastic OM should be investigated further.- - - - - - - - - - ranking = 2keywords = antigen (Clic here for more details about this article) |