1. Seroprevalence of aquaporin-4-IgG in a northern California population representative cohort of multiple sclerosis.
- Author
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Pittock SJ, Lennon VA, Bakshi N, Shen L, McKeon A, Quach H, Briggs FB, Bernstein AL, Schaefer CA, and Barcellos LF
- Subjects
- Adult, Aged, Aquaporin 4 immunology, Autoantibodies blood, California, Cohort Studies, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Multiple Sclerosis immunology, Myelitis, Transverse blood, Myelitis, Transverse diagnosis, Optic Neuritis diagnosis, Optic Neuritis immunology, Seroepidemiologic Studies, Aquaporin 4 blood, Immunoglobulin G blood, Multiple Sclerosis blood
- Abstract
Importance: Using an aquaporin-4 (AQP4) M1-isoform-specific enzyme-linked immunosorbent assay (ELISA) and a fixed transfected cell-based assay (CBA), we tested AQP4-IgG in a northern California population representative cohort of 3293 potential cases with multiple sclerosis (MS). Seropositive cases were tested additionally by fluorescence-activated cell sorting, a live transfected cell-based assay., Observations: Sera samples were available in 1040 cases; 7 yielded positive results, 4 by ELISA alone and 3 by both ELISA and CBA. Clinical data (episodes of optic neuritis and longitudinally extensive transverse myelitis [reported on at least 1 magnetic resonance imaging spine]) supported the alternative diagnosis of neuromyelitis optica for 2 patients as seropositive by both ELISA and CBA. These 2 patients alone tested positive by a fluorescence-activated cell-sorting assay. The diagnosis of MS was considered correct in the other 5 patients. Thus, 5 ELISA results and 1 fixed CBA result were false positive., Conclusions and Relevance: Sensitive serological evaluation for AQP4-IgG in this large population-representative cohort of predominantly white non-Hispanic patients with MS reveals that neuromyelitis optica spectrum disorder is rarely misdiagnosed as MS in contemporary US neurological practice (0.2%). The frequency of a false-positive result for ELISA and CBA in this MS cohort were 0.5% and 0.1%, respectively. This finding reflects the superior specificity of CBA and justifies caution in interpreting AQP4-IgG results obtained by ELISA.
- Published
- 2014
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