Microtubule‐associated protein 1B: Novel paraneoplastic biomarker

• Published in: Annals of neurology Vol. 81; no. 2; pp. 266 - 277
• Main Authors: Gadoth, Avi, Kryzer, Thomas J., Fryer, Jim, McKeon, Andrew, Lennon, Vanda A., Pittock, Sean J.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.02.2017
• Subjects: Animals; Antibodies; Antigens; Ataxia; Autoantibodies; Autoantibodies - immunology; Autoantigens - immunology; Biomarkers; Biomarkers, Tumor - immunology; Brain; Cerebellar ataxia; Cerebellum; Cerebrospinal fluid; Disease control; Encephalopathy; Epidermal growth factor; Evaluation; Humans; Immunoglobulin G; Immunoglobulin G - immunology; Lung carcinoma; Lung Neoplasms - diagnosis; Lung Neoplasms - immunology; Mass spectrometry; Mass spectroscopy; Mice; Microtubule-associated protein 1; Microtubule-Associated Proteins - immunology; Neurological diseases; Paraneoplastic Syndromes, Nervous System - blood; Paraneoplastic Syndromes, Nervous System - cerebrospinal fluid; Paraneoplastic Syndromes, Nervous System - immunology; Patients; Peripheral neuropathy; Proteins; Purkinje Cells - immunology; Recombinant Proteins; Rodents; Small cell lung carcinoma; Small Cell Lung Carcinoma - diagnosis; Small Cell Lung Carcinoma - immunology
• ISSN: 0364-5134; 1531-8249; 1531-8249
• DOI: 10.1002/ana.24872

Objective To report the identification of microtubule‐associated protein (MAP) 1B as the antigen of the previously described Purkinje cell cytoplasmic antibody type 2 (PCA‐2) antibody, its frequency, and clinical, oncological, and serological associations. Methods Archival serum or cerebrospinal fluid (CSF) specimens were available from 96 of 118 consecutive PCA‐2‐IgG–seropositive patients identified during 1993–2016. The autoantigen, defined in mouse brain lysate by Western blot and mass spectrometry, was confirmed by dual immunohistochemical staining using commercial antibodies. The major antigenic region was defined by Western blot using recombinant protein fragments. Results IgG in 95 of 96 patients’ serum or CSF (but in none of 98 healthy or disease control subjects’ serum specimens) bound to recombinant MAP1B. A minority (17.5%) of patients’ IgG also bound to MAP1A. PCA‐2 was often accompanied by additional neural autoantibody markers of small‐cell carcinoma, including collapsin response‐mediated protein 5 (CRMP5) IgG (26%) or antineuronal nuclear antibody type 1 (ANNA‐1) IgG (also known as anti‐Hu; 13%). Neurological manifestations in 95 patients were (in decreasing frequency): peripheral neuropathy, 53%; cerebellar ataxia, dysmetria, or dysarthria, 38%; and encephalopathy, 27%. Cancer (majority small‐cell lung carcinoma [SCLC]) was detected in 66 of 84 evaluated patients (79%). The MAP1B (PCA‐2) autoantibody detection rate, among approximately 70,000 patients undergoing service neural autoantibody evaluation in 2015, was 0.024%, equaling amphiphysin IgG (0.026%) and more common than ANNA‐2 (also known as anti‐Ri; 0.016%) and PCA‐Tr (also known as delta/notch‐like epidermal growth factor‐related receptor [DNER]; 0.006%). Interpretation MAP1B, the PCA‐2 autoantigen, represents a novel target in paraneoplastic neurological disorders and has high predictive value for SCLC. Its relatively high prevalence, compared with other recognized paraneoplastic neural autoantibodies, justifies its testing in comprehensive paraneoplastic neural autoantibody evaluation. Ann Neurol 2017;81:266–277