TY - JOUR
T1 - Updated estimate of AQP4-IgG serostatus and disability outcome in neuromyelitis optica
AU - Jiao, Yujuan
AU - Fryer, James P.
AU - Lennon, Vanda A.
AU - Jenkins, Sarah M.
AU - Quek, Amy M.L.
AU - Smith, Carin Y.
AU - McKeon, Andrew
AU - Costanzi, Chiara
AU - Iorio, Raffaele
AU - Weinshenker, Brian G.
AU - Wingerchuk, Dean M.
AU - Shuster, Elizabeth A.
AU - Lucchinetti, Claudia F.
AU - Pittock, Sean J.
PY - 2013/10/1
Y1 - 2013/10/1
N2 - Objective: To 1) determine, using contemporary recombinant antigen-based assays, the aquaporin-4 (AQP4)-immunoglobulin G (IgG) detection rate in sequential sera of patients assigned a clinical diagnosis of neuromyelitis optica (NMO) but initially scored negative by tissue-based indirect immunofluorescence (IIF) assay and 2) evaluate the impact of serostatus on phenotype and outcome. Methods: From Mayo Clinic records (2005-2011), we identified 163 patients with NMO 110 (67%) were seropositive by IIF and 53 (33%) were scored seronegative. Available stored sera from 49 " seronegative" patients were tested by ELISA, AQP4-transfected cell-based assay, and in-house fluorescence-activated cell sorting assay. Clinical characteristics were compared based on final serostatus. Results: Thirty of the 49 IIF-negative patients (61%) were reclassified as seropositive, yielding an overall AQP4-IgG seropositivity rate of 88% (i.e., 12% seronegative). The fluorescence-activated cell sorting assay improved the detection rate to 87%, cell-based assay to 84%, and ELISA to 79%. The sex ratio (female to male) was 1:1 for seronegatives and 9:1 for seropositives (p , 0.0001). Simultaneous optic neuritis and transverse myelitis as onset attack type (i.e., within 30 days of each other) occurred in 32% of seronegatives and in 3.6% of seropositives (p , 0.0001). Relapse rate, disability outcome, and other clinical characteristics did not differ significantly. Conclusions: Serological tests using recombinant AQP4 antigen are significantly more sensitive than tissue-based IIF for detecting AQP4-IgG. Testing should precede immunotherapy. If negative later-drawn specimens should be tested. aqp4-igg-seronegative nmo is less frequent than previously reported and is clinically similar to aqp4-igg-seropositive NMO.
AB - Objective: To 1) determine, using contemporary recombinant antigen-based assays, the aquaporin-4 (AQP4)-immunoglobulin G (IgG) detection rate in sequential sera of patients assigned a clinical diagnosis of neuromyelitis optica (NMO) but initially scored negative by tissue-based indirect immunofluorescence (IIF) assay and 2) evaluate the impact of serostatus on phenotype and outcome. Methods: From Mayo Clinic records (2005-2011), we identified 163 patients with NMO 110 (67%) were seropositive by IIF and 53 (33%) were scored seronegative. Available stored sera from 49 " seronegative" patients were tested by ELISA, AQP4-transfected cell-based assay, and in-house fluorescence-activated cell sorting assay. Clinical characteristics were compared based on final serostatus. Results: Thirty of the 49 IIF-negative patients (61%) were reclassified as seropositive, yielding an overall AQP4-IgG seropositivity rate of 88% (i.e., 12% seronegative). The fluorescence-activated cell sorting assay improved the detection rate to 87%, cell-based assay to 84%, and ELISA to 79%. The sex ratio (female to male) was 1:1 for seronegatives and 9:1 for seropositives (p , 0.0001). Simultaneous optic neuritis and transverse myelitis as onset attack type (i.e., within 30 days of each other) occurred in 32% of seronegatives and in 3.6% of seropositives (p , 0.0001). Relapse rate, disability outcome, and other clinical characteristics did not differ significantly. Conclusions: Serological tests using recombinant AQP4 antigen are significantly more sensitive than tissue-based IIF for detecting AQP4-IgG. Testing should precede immunotherapy. If negative later-drawn specimens should be tested. aqp4-igg-seronegative nmo is less frequent than previously reported and is clinically similar to aqp4-igg-seropositive NMO.
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U2 - 10.1212/WNL.0b013e3182a6cb5c
DO - 10.1212/WNL.0b013e3182a6cb5c
M3 - Article
C2 - 23997151
AN - SCOPUS:84888372951
SN - 0028-3878
VL - 81
SP - 1197
EP - 1204
JO - Neurology
JF - Neurology
IS - 14
ER -