Testing for antibodies to human aquaporin-4 by ELISA: Sensitivity, specificity, and direct comparison with immunohistochemistry

S. Jarius, D. Franciotta, F. Paul, R. Bergamaschi, P. S. Rommer, K. Ruprecht, M. Ringelstein, O. Aktas, W. Kristoferitsch, B. Wildemann

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)32-37
Number of pages6
JournalJournal of the Neurological Sciences
Volume320
Issue number1-2
DOIs
Publication statusPublished - Sep 15 2012

Fingerprint

Aquaporin 4
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Sensitivity and Specificity
Antibodies
Immunoglobulin G
Transverse Myelitis
Neuromyelitis Optica
Serum

Keywords

  • Antibody to aquaporin-4
  • Diagnosis
  • Enzyme-linked immunosorbent assay (ELISA)
  • Indirect immunofluorescence
  • Longitudinally extensive transverse myelitis
  • Multiple sclerosis
  • Neuromyelitis optica (Devic's syndrome)
  • NMO-IgG
  • Optic neuritis
  • Recombinant antigen

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Testing for antibodies to human aquaporin-4 by ELISA : Sensitivity, specificity, and direct comparison with immunohistochemistry. / Jarius, S.; Franciotta, D.; Paul, F.; Bergamaschi, R.; Rommer, P. S.; Ruprecht, K.; Ringelstein, M.; Aktas, O.; Kristoferitsch, W.; Wildemann, B.

In: Journal of the Neurological Sciences, Vol. 320, No. 1-2, 15.09.2012, p. 32-37.

Research output: Contribution to journalArticle

Jarius, S. ; Franciotta, D. ; Paul, F. ; Bergamaschi, R. ; Rommer, P. S. ; Ruprecht, K. ; Ringelstein, M. ; Aktas, O. ; Kristoferitsch, W. ; Wildemann, B. / Testing for antibodies to human aquaporin-4 by ELISA : Sensitivity, specificity, and direct comparison with immunohistochemistry. In: Journal of the Neurological Sciences. 2012 ; Vol. 320, No. 1-2. pp. 32-37.
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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.

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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.

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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

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