TY - JOUR
T1 - Testing for antibodies to human aquaporin-4 by ELISA
T2 - Sensitivity, specificity, and direct comparison with immunohistochemistry
AU - Jarius, S.
AU - Franciotta, D.
AU - Paul, F.
AU - Bergamaschi, R.
AU - Rommer, P. S.
AU - Ruprecht, K.
AU - Ringelstein, M.
AU - Aktas, O.
AU - Kristoferitsch, W.
AU - Wildemann, B.
PY - 2012/9/15
Y1 - 2012/9/15
N2 - Background: Several assays have been developed to detect antibodies to aquaporin-4 (NMO-IgG/AQP4-Ab). However, many of these assays require sophisticated techniques and are thus only available at specialized laboratories. This is problematic since NMO-IgG/AQP4-Ab testing has important prognostic and therapeutic implications. Objective: To evaluate a newly developed, commercial, enzyme-linked immunosorbent assay (ELISA) for detecting NMO-IgG/AQP4-Ab. Methods: Serum samples from 261 patients with NMO spectrum disorders (NMOSD; n = 108) and controls (n = 153) were tested for AQP4-Ab by using ELISA. Of these patients, 207 were tested in parallel using a standard immunohistochemical (IHC) assay. Results: Fifty of 66 (75.8%) patients with NMO, 17/25 (68%) with LETM, 3/14 (21.4%) with ON, 2/3 (66.7%) with ON and non-extensive transverse myelitis, and 2/153 (1.3%) controls tested positive in the ELISA. Of those NMOSD patients tested by both ELISA and IHC, 10 were positive only in the ELISA and 3 exclusively in the IHC assay, suggesting that the overall sensitivity of the ELISA was higher than that of the standard IHC assay. The ELISA yielded very good intra- and inter-run reproducibility with regard to AQP4-Ab detection and good intrarun, but only moderate inter-run reproducibility with regard to AQP4-Ab quantification. Anti-AQP4 serum concentrations correlated with disease activity (p <0.00001), but did not differ between patients with NMO and patients with isolated LETM or ON. Conclusion: The ELISA evaluated here provides a relatively sensitive and easy-to-use diagnostic tool for detecting antibodies to AQP4 and could make AQP4-Ab testing, which is of high clinical relevance, more widely available.
AB - Background: Several assays have been developed to detect antibodies to aquaporin-4 (NMO-IgG/AQP4-Ab). However, many of these assays require sophisticated techniques and are thus only available at specialized laboratories. This is problematic since NMO-IgG/AQP4-Ab testing has important prognostic and therapeutic implications. Objective: To evaluate a newly developed, commercial, enzyme-linked immunosorbent assay (ELISA) for detecting NMO-IgG/AQP4-Ab. Methods: Serum samples from 261 patients with NMO spectrum disorders (NMOSD; n = 108) and controls (n = 153) were tested for AQP4-Ab by using ELISA. Of these patients, 207 were tested in parallel using a standard immunohistochemical (IHC) assay. Results: Fifty of 66 (75.8%) patients with NMO, 17/25 (68%) with LETM, 3/14 (21.4%) with ON, 2/3 (66.7%) with ON and non-extensive transverse myelitis, and 2/153 (1.3%) controls tested positive in the ELISA. Of those NMOSD patients tested by both ELISA and IHC, 10 were positive only in the ELISA and 3 exclusively in the IHC assay, suggesting that the overall sensitivity of the ELISA was higher than that of the standard IHC assay. The ELISA yielded very good intra- and inter-run reproducibility with regard to AQP4-Ab detection and good intrarun, but only moderate inter-run reproducibility with regard to AQP4-Ab quantification. Anti-AQP4 serum concentrations correlated with disease activity (p <0.00001), but did not differ between patients with NMO and patients with isolated LETM or ON. Conclusion: The ELISA evaluated here provides a relatively sensitive and easy-to-use diagnostic tool for detecting antibodies to AQP4 and could make AQP4-Ab testing, which is of high clinical relevance, more widely available.
KW - Antibody to aquaporin-4
KW - Diagnosis
KW - Enzyme-linked immunosorbent assay (ELISA)
KW - Indirect immunofluorescence
KW - Longitudinally extensive transverse myelitis
KW - Multiple sclerosis
KW - Neuromyelitis optica (Devic's syndrome)
KW - NMO-IgG
KW - Optic neuritis
KW - Recombinant antigen
UR - http://www.scopus.com/inward/record.url?scp=84864586006&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864586006&partnerID=8YFLogxK
U2 - 10.1016/j.jns.2012.06.002
DO - 10.1016/j.jns.2012.06.002
M3 - Article
C2 - 22705047
AN - SCOPUS:84864586006
VL - 320
SP - 32
EP - 37
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
SN - 0022-510X
IS - 1-2
ER -