1/3. Paraneoplastic ophthalmoplegia and subacute motor axonal neuropathy associated with anti-GQ1b antibodies in a patient with malignant melanoma.A 68 year old woman developed oculomotor paresis shortly after metastatic progression of her melanoma was discovered. She was then immunised with the tumour antigen MAGE-3 in combination with an immunological adjuvant. During immunisation her symptoms worsened and she developed severe, predominantly proximal axonal motor neuropathy and became bedridden. IgM antibodies against gangliosides GM2, GD3, and GQ1b were detected in serum obtained two weeks before and nine weeks after the onset of symptoms. Immunohistochemically, the patient's IgM reacted with the tumour and co-localised with GQ1b. She improved neurologically following steroid treatment and became ambulatory.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/3. Anti-neuronal nuclear autoantibody type 2: paraneoplastic accompaniments.We identified the IgG autoantibody ANNA-2 ("anti-Ri") in 34 patients in a 12-year period by immunofluorescence screening of sera from approximately 75000 patients with subacute neurological disorders that were suspected to be paraneoplastic. Detailed clinical information was available for 28 patients (10 men, 18 women). Cancer was diagnosed in 24 patients (86%); 21 had histologically proven carcinoma (10 lung, 9 breast, 1 cervical, 1 bladder), and 3 had an intrathoracic imaging abnormality. Cancer anteceded neurological symptoms in 4 of 28 patients. Cancer detection frequency increased with continued surveillance. Neurological disorders, in decreasing frequency, were brainstem syndrome (including opsoclonus, myoclonus, or both), cerebellar syndrome, myelopathy, peripheral neuropathy, cranial neuropathy, movement disorder, encephalopathy, Lambert-Eaton syndrome, and seizures. Four patients had laryngospasm and four had jaw opening dystonia (two with neck dystonia). Nine (32%) were wheelchair-bound 1 month after neurological symptom onset. Most improved neurologically after immunomodulatory or tumor-directed therapy. Accompanying autoantibodies, found in 73% of sera, included ANNA-1, ANNA-3, CRMP-5-IgG, P/Q-type and N-type Ca(2 ) channel antibodies, and muscle-type acetylcholine receptor antibody. Some neurological accompaniments of ANNA-2 may reflect potentially pathogenic humoral or cell-mediated responses to coimmunogenic tumor antigens, for example, Lambert-Eaton syndrome (P/Q-type Ca(2 ) channel antibody) and peripheral neuropathy (ANNA-1 effector T cells).- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
3/3. gangliosides act as onconeural antigens in paraneoplastic neuropathies.We describe two patients with progressive neuropathy and lung cancer in whom gangliosides (GS) may represent the oncoantigens. Patient 1 had motor neuropathy, high titers of IgG1 and IgG3 to GD1a and GM1, and expansion of circulating gamma-delta T lymphocytes, a T-cell subset responding to glycolipids. Patient 2 presented with Miller-Fisher-like syndrome and IgG3 activity to disialo-GS. In both cases, decreased autoimmune responses and stabilization of neuropathy were accomplished by tumor treatment. By immunohistochemistry, patient 1's IgG bound to his own tumor and to structures of normal nervous system expressing GD1a or GM1. Infiltration of IgG in the same neural structures was found at his autopsy. Regarding cellular immunity, the proportion of gamma-delta T lymphocytes infiltrating carcinoma from patient 1 was significantly higher than in neoplastic controls. These results indicate that GS may represent onconeural antigens in paraneoplastic neuropathy (PNN); their expression on neoplastic tissue may elicit autoimmune responses, which also target neural structures.- - - - - - - - - - ranking = 6keywords = antigen (Clic here for more details about this article) |