Hu Antigen Specificities of ANNA-I Autoantibodies in Paraneoplastic Neurological Disease

• Published in: Journal of autoimmunity Vol. 13; no. 4; pp. 435 - 443
• Main Authors: King, P.H, Redden, D, Palmgren, J.S, Nabors, L.B, Lennon, V.A
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 01-12-1999; Elsevier
• Subjects: AHu antigen; Antigens, Surface - genetics; Antigens, Surface - immunology; Autoantibodies - blood; Autoantibodies - immunology; Biological and medical sciences; ELAV Proteins; ELAV-Like Protein 1; ELAV-Like Protein 2; ELAV-Like Protein 3; ELAV-Like Protein 4; Enzyme-Linked Immunosorbent Assay - methods; Hel-N1, HuC, HuD, HuR, RNA-binding proteins; Humans; Medical sciences; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - immunology; Nervous system involvement in other diseases. Miscellaneous; Neurology; Paraneoplastic Syndromes, Nervous System - blood; Paraneoplastic Syndromes, Nervous System - immunology; Paraneoplastic Syndromes, Nervous System - physiopathology; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; RNA-Binding Proteins - genetics; RNA-Binding Proteins - immunology; Hel-N1, HuC, HuD, HuR, RNA-binding proteins; Autoimmunity; Human; Nervous system diseases; Immune response; Encephalomyelitis; Antibody; Autoantibody; Neuropathy; Cerebral disorder; Antigen; Autoantigen; Immunological investigation; Central nervous system disease; Sensory nerve; Paraneoplastic syndrome; Spinal cord disease
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1006/jaut.1999.0337

Despite a broad clinical spectrum, paraneoplastic enecephalomyelitis/sensory neuronopathy (PEM/SSN) is characterized by the presence of a common autoantibody, referred to as anti-Hu or type I anti-neuronal nuclear antibody (ANNA-1). The target of these antibodies is a family of four Hu antigens: three (Hel-N1, HuC, HuD) are neural-specific, while the fourth (HuR) is ubiquitous. Here, we have analysed by enzyme-linked immunosorbent assay (ELISA) the immunoreactivity of all four Hu antigens in serum from 75 patients with ANNA-1 autoantibodies and looked for clinical correlations. IgG in all the patients' sera bound to each of the four antigens, and the titers correlated with those of the ANNA-I immunofluorescence assay. Median titers for the neural-specific antigens (range: 56,892–90,051) were significantly higher than for HuR (36,799). Patients with gastrointestinal dysmotility or subacute sensory neuronopathy had the highest median titers to all four antigens, while patients with sensorineural deafness had the lowest titers. The results indicate a heterogeneous immune response to individual Hu antigens in patients with PEM/SSN, and that the titers to these antigens as a group, rather than individually, correlate with clinical profile. Furthermore, these results suggest that ELISA analysis of a single neural-specific Hu antigen is sufficient for serological screening in PEM/SSN.