ANNA-3 anti-neuronal nuclear antibody: Marker of lung cancer-related autoimmunity

• Published in: Annals of neurology Vol. 50; no. 3; pp. 301 - 311
• Main Authors: Chan, Koon Ho, Vernino, Steven, Lennon, Vanda A.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.09.2001; Willey-Liss
• Subjects: Adult; Aged; Aged, 80 and over; Animals; Antibodies, Antinuclear - blood; Antibody Specificity; Autoimmunity - immunology; Biological and medical sciences; Biomarkers - blood; Carcinoma, Small Cell - blood; Carcinoma, Small Cell - immunology; Cerebellum - immunology; Child; Digestive System - immunology; Female; Humans; Immunoglobulin G - blood; Kidney - immunology; Lung Neoplasms - blood; Lung Neoplasms - immunology; Male; Medical sciences; Mice; Middle Aged; Paraneoplastic Syndromes, Nervous System - blood; Paraneoplastic Syndromes, Nervous System - immunology; Pneumology; Tumors of the respiratory system and mediastinum; Autoimmunity; Human; Lung disease; Nervous system diseases; Respiratory disease; Antibody; Cell nucleus; Biological marker; Malignant tumor; Bronchopulmonary; Neuron; Bronchus disease; Complication; Paraneoplastic syndrome
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.1127

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.