Seroprevalence of aquaporin-4-IgG in a Northern California population representative cohort of multiple sclerosis

Sean J. Pittock, Vanda A. Lennon, Nandini Bakshi, Ling Shen, Andrew McKeon, Hong Quach, Farren B.S. Briggs, Allan L. Bernstein, Catherine A. Schaefer, Lisa F. Barcellos

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


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 transversemyelitis [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.

Original languageEnglish (US)
Pages (from-to)1433-1436
Number of pages4
JournalJAMA neurology
Issue number11
StatePublished - Nov 1 2014

ASJC Scopus subject areas

  • Clinical Neurology


Dive into the research topics of 'Seroprevalence of aquaporin-4-IgG in a Northern California population representative cohort of multiple sclerosis'. Together they form a unique fingerprint.

Cite this