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Arch Neurol — Abstract: Quantification and Functional Characterization of Antibodies to Native Aquaporin 4 in Neuromyelitis Optica, October 2010, Kalluri et al. 67 (10): 1201

Quantification and Functional Characterization of Antibodies to Native Aquaporin 4 in Neuromyelitis Optica

Sudhakar Reddy Kalluri, MSc; Zsolt Illes, MD; Rajneesh Srivastava, MSc; Bruce Cree, MD; Til Menge, MD; Jeffrey L. Bennett, MD, PhD; Achim Berthele, MD; Bernhard Hemmer, MD

Arch Neurol.?2010;67(10):1201-1208. doi:10.1001/archneurol.2010.269

Background? Antibodies targeting membrane proteins playan important role in various autoimmune diseases of the nervoussystem. So far, assays allowing proper analysis of such autoantibodiesare largely missing. A serum autoantibody to aquaporin 4 (AQP4)is associated with neuromyelitis optica (NMO). Although severalassays are able to detect this autoantibody, they do not allowdetermination of the biological activity of anti-AQP4 antibodies.

Objective? To develop a bioassay for quantification andcharacterization of human anti-AQP4 antibodies.

Design, Setting, and Participants? We developed a novelbioassay for quantification and characterization of human anti-AQP4antibodies based on high-level expression of native AQP4 (nAQP4)protein on the surface of human astroglioma cells. The testwas validated in 2 independent cohorts of patients with NMOspectrum disease.

We detected anti-nAQP4-IgG with a sensitivityof 57.9% and specificity of 100% in patients with NMO spectrumdiseases, suggesting that our bioassay is at least as sensitiveand specific as the gold-standard NMO-IgG assay. The anti-AQP4antibodies belonged predominantly to the IgG1 isotype and boundwith high affinity to the extracellular domain of nAQP4. Ourdata suggest that the autoantibody exerts pathological propertiesbecause nAQP4-IgG–positive sera induced cell death ofnAQP4-expressing cells by antibody-dependent cellular naturalkiller cell cytotoxic effect and complement activation. Furthermore,nAQP4-IgG titers strongly correlated with in vitro cytotoxiceffect.

Conclusions? In NMO, this assay may help to unravel thebiological function of anti-nAQP4-IgG. Our findings demonstratethe potential of bioassays to characterize biologically relevantantibodies in human autoimmune diseases.

Read More: Arch Neurol — Abstract: Quantification and Functional Characterization of Antibodies to Native Aquaporin 4 in Neuromyelitis Optica, October 2010, Kalluri et al. 67 (10): 1201