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  • Title: Aquaporin-4 autoantibodies in a paraneoplastic context.
    Author: Pittock SJ, Lennon VA.
    Journal: Arch Neurol; 2008 May; 65(5):629-32. PubMed ID: 18474738.
    Abstract:
    BACKGROUND: The neuromyelitis optica IgG autoantibody (NMO-IgG) is a validated biomarker for NMO and an emerging spectrum of inflammatory central nervous system-demyelinating disorders. Its antigen is the astrocytic water channel aquaporin-4; NMO-IgG has not been described in a cancer context. OBJECTIVES: To report (1) neurologic and oncologic correlates for patients incidentally identified as NMO-IgG seropositive in a blinded evaluation for paraneoplastic autoantibodies and (2) the frequency of cancer in NMO-IgG-seropositive patients. DESIGN: Observational, retrospective case series. SETTING: Neuroimmunology Laboratory and Neurology Clinical Practice, Mayo Clinic College of Medicine. PATIENTS AND METHODS: From 1998 to 2007, we detected NMO-IgG in 2 patient groups: (1) 31 patients (88% female) identified incidentally among 180 000 patients evaluated for paraneoplastic autoantibodies and (2) 141 patients identified through physician-requested serological evaluation for a suspected NMO-spectrum disorder. RESULTS: In the first group, clinical information was available for 28 patients (90%). An NMO-spectrum disorder was diagnosed in 26 patients (93%), of whom 6 had a neoplasm (5 carcinomas [2 breast, 1 lung, 1 thymic, and 1 uterine cervical] and 1 B-cell lymphoma) and 1 had monoclonal gammopathy. In 4 patients, NMO-related symptoms followed neoplasia detection (median, 14 [range 3-18] months), and in 2 patients, symptoms preceded neoplasia detection (by 5 and 3 months). Two patients had carcinoma (1 breast and 1 lung) without neurological evidence of an NMO-spectrum disorder. In the second group, neoplasms were recorded in 7 seropositive patients (5.0%) with a clinically diagnosed NMO-spectrum disorder: 3 carcinomas (all breast), 1 thyroid Hürthle cell, 1 carcinoid, 1 pituitary somatotropinoma, and 1 B-cell lymphoma. An eighth patient had monoclonal gammopathy. CONCLUSIONS: Aquaporin-4-specific IgG in some cases of NMO may reflect a paraneoplastic immune response. The clinical utility of this autoantibody as a cancer marker warrants prospective investigation.
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