TY - JOUR
T1 - Aquaporin-4 antibody testing
T2 - Direct comparison of M1-AQP4-DNA-transfected cells with leaky scanning versus M23-AQP4-DNA-transfected cells as antigenic substrate
AU - Jarius, Sven
AU - Paul, Friedemann
AU - Fechner, Kai
AU - Ruprecht, Klemens
AU - Kleiter, Ingo
AU - Franciotta, Diego
AU - Ringelstein, Marius
AU - Pache, Florence
AU - Aktas, Orhan
AU - Wildemann, Brigitte
PY - 2014/7/29
Y1 - 2014/7/29
N2 - Background: Neuromyelitis optica (NMO, Devic syndrome) is associated with antibodies to aquaporin-4 (NMO-IgG/AQP4-Ab) in the majority of cases. NMO-IgG/AQP4-Ab seropositivity in patients with NMO and its spectrum disorders has important differential diagnostic, prognostic and therapeutic implications. So-called cell-based assays (CBA) are thought to provide the best AQP4-Ab detection rates.Objective: To compare directly the AQP4-IgG detection rates of the currently most widely used commercial CBA, which employs cells transfected with a full-length (M1)-human AQP4 DNA in a fashion that allows leaky scanning (LS) and thus expression of M23-AQP4 in addition to M1-AQP, to that of a newly developed CBA from the same manufacturer employing cells transfected with human M23-AQP4-DNA. Methods: Results from 368 serum samples that had been referred for routine AQP4-IgG determination and had been tested in parallel in the two assays were compared. Results: Seventy-seven out of 368 samples (20.9%) were positive for NMO-IgG/AQP4-Ab in at least one assay. Of these, 73 (94.8%) were positive in both assays. A single sample (1.3%) was exclusively positive in the novel assay; three samples (3.9%) were unequivocally positive only in the 'classic' assay due to high background intensity in the novel assay. Both median fluorescence intensity and background intensity were higher in the new assay. Conclusions: This large study did not reveal significant differences in AQP4-IgG detection rates between the 'classic' CBA and a new M23-DNA-based CBA. Importantly, our results largely re-affirm the validity of previous studies that had used the 'classic' AQP4-CBA to establish NMO-IgG/AQP4-Ab seropositivity rates in NMO and in a variety of NMO spectrum disorders.
AB - Background: Neuromyelitis optica (NMO, Devic syndrome) is associated with antibodies to aquaporin-4 (NMO-IgG/AQP4-Ab) in the majority of cases. NMO-IgG/AQP4-Ab seropositivity in patients with NMO and its spectrum disorders has important differential diagnostic, prognostic and therapeutic implications. So-called cell-based assays (CBA) are thought to provide the best AQP4-Ab detection rates.Objective: To compare directly the AQP4-IgG detection rates of the currently most widely used commercial CBA, which employs cells transfected with a full-length (M1)-human AQP4 DNA in a fashion that allows leaky scanning (LS) and thus expression of M23-AQP4 in addition to M1-AQP, to that of a newly developed CBA from the same manufacturer employing cells transfected with human M23-AQP4-DNA. Methods: Results from 368 serum samples that had been referred for routine AQP4-IgG determination and had been tested in parallel in the two assays were compared. Results: Seventy-seven out of 368 samples (20.9%) were positive for NMO-IgG/AQP4-Ab in at least one assay. Of these, 73 (94.8%) were positive in both assays. A single sample (1.3%) was exclusively positive in the novel assay; three samples (3.9%) were unequivocally positive only in the 'classic' assay due to high background intensity in the novel assay. Both median fluorescence intensity and background intensity were higher in the new assay. Conclusions: This large study did not reveal significant differences in AQP4-IgG detection rates between the 'classic' CBA and a new M23-DNA-based CBA. Importantly, our results largely re-affirm the validity of previous studies that had used the 'classic' AQP4-CBA to establish NMO-IgG/AQP4-Ab seropositivity rates in NMO and in a variety of NMO spectrum disorders.
KW - antibodies to aquaporin-4
KW - antibody testing
KW - cell-based assay
KW - Devic syndrome
KW - Devic's syndrome
KW - longitudinally extensive transverse myelitis
KW - M1 aquaporin-4
KW - M23 aquaporin-4
KW - neuromyelitis optica
KW - neuromyelitis optica spectrum disorders
KW - NMO-IgG
KW - optica neuritis
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U2 - 10.1186/1742-2094-11-129
DO - 10.1186/1742-2094-11-129
M3 - Article
C2 - 25074611
AN - SCOPUS:84904769688
VL - 11
JO - Journal of Neuroinflammation
JF - Journal of Neuroinflammation
SN - 1742-2094
IS - 1
M1 - 129
ER -