Diagnosis of neuromyelitis spectrum disorders: Comparative sensitivities and specificities of immunohistochemical and immunoprecipitation assays

Andrew B McKeon, James P. Fryer, Metha Apiwattanakul, Vanda A Lennon, Shannon R. Hinson, Thomas J. Kryzer, Claudia F Lucchinetti, Brian G Weinshenker, Dean Marko Wingerchuk, Elizabeth A. Shuster, Sean J Pittock

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Objective: To compare the sensitivity and specificity of immunofluorescence (IF) and immunoprecipitation (IP) assays using green fluorescent protein-tagged aquaporin-4 (AQP4) in 6335 patients for whom serological evaluation was requested on a service basis. Design: Case-control study. Setting: Mayo Clinic Neuroimmunology Laboratory (Rochester, Minnesota) and Departments of Neurology (Rochester, Minnesota; Scottsdale, Arizona; and Jacksonville, Florida). Patients: Group 1, 835 Mayo Clinic patients, 100 with a neuromyelitis optica (NMO) spectrum disorder diagnosis and 735 without NMO spectrum disorder; group 2, 5500 non-Mayo Clinic patients. Main Outcome Measure: Sensitivity and specificity of each assay for NMO or NMO spectrum disorder, individually and combined. Results: In group 1, the sensitivity rates for NMO were IF, 58%; IP, 33%; and combined assays, 63%. The sensitivity rates for relapsing longitudinally extensive transverse myelitis were IF, 29%; IP, 6%; and combined assays, 29%. The specificity rates for NMO and relapsing longitudinally extensive transverse myelitis were IF, 99.6%; IP, 99.3%; and combined assays, 99.2%. In group 2, NMO-IgG was detected by IF in 498 of 5500 patients (9.1%) and by IP in 331 patients (6.0%); 76 of the 331 patients seropositive by IP (23%) were negative by IF. Clinical information was available for 124 patients (including 16 of those seropositive by IP only); 123 had a definite NMO spectrum disorder and 1 was at risk for NMO (monophasic optic neuritis). Conclusions: In this large, clinical practice-based study, NMO-IgG detected by IF or IP was highly specific for NMO spectrum disorders. The IP assay was significantly less sensitive than IF. Combined testing improved sensitivity by 5%.

Original languageEnglish (US)
Pages (from-to)1134-1138
Number of pages5
JournalArchives of Neurology
Volume66
Issue number9
DOIs
StatePublished - Sep 2009

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Neuromyelitis Optica
Immunoprecipitation
Fluorescent Antibody Technique
Sensitivity and Specificity
Transverse Myelitis
Specificity
Immunoglobulin G
Aquaporin 4
Optic Neuritis
Neurology
Green Fluorescent Proteins
Case-Control Studies

ASJC Scopus subject areas

  • Clinical Neurology

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Diagnosis of neuromyelitis spectrum disorders : Comparative sensitivities and specificities of immunohistochemical and immunoprecipitation assays. / McKeon, Andrew B; Fryer, James P.; Apiwattanakul, Metha; Lennon, Vanda A; Hinson, Shannon R.; Kryzer, Thomas J.; Lucchinetti, Claudia F; Weinshenker, Brian G; Wingerchuk, Dean Marko; Shuster, Elizabeth A.; Pittock, Sean J.

In: Archives of Neurology, Vol. 66, No. 9, 09.2009, p. 1134-1138.

Research output: Contribution to journalArticle

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abstract = "Objective: To compare the sensitivity and specificity of immunofluorescence (IF) and immunoprecipitation (IP) assays using green fluorescent protein-tagged aquaporin-4 (AQP4) in 6335 patients for whom serological evaluation was requested on a service basis. Design: Case-control study. Setting: Mayo Clinic Neuroimmunology Laboratory (Rochester, Minnesota) and Departments of Neurology (Rochester, Minnesota; Scottsdale, Arizona; and Jacksonville, Florida). Patients: Group 1, 835 Mayo Clinic patients, 100 with a neuromyelitis optica (NMO) spectrum disorder diagnosis and 735 without NMO spectrum disorder; group 2, 5500 non-Mayo Clinic patients. Main Outcome Measure: Sensitivity and specificity of each assay for NMO or NMO spectrum disorder, individually and combined. Results: In group 1, the sensitivity rates for NMO were IF, 58{\%}; IP, 33{\%}; and combined assays, 63{\%}. The sensitivity rates for relapsing longitudinally extensive transverse myelitis were IF, 29{\%}; IP, 6{\%}; and combined assays, 29{\%}. The specificity rates for NMO and relapsing longitudinally extensive transverse myelitis were IF, 99.6{\%}; IP, 99.3{\%}; and combined assays, 99.2{\%}. In group 2, NMO-IgG was detected by IF in 498 of 5500 patients (9.1{\%}) and by IP in 331 patients (6.0{\%}); 76 of the 331 patients seropositive by IP (23{\%}) were negative by IF. Clinical information was available for 124 patients (including 16 of those seropositive by IP only); 123 had a definite NMO spectrum disorder and 1 was at risk for NMO (monophasic optic neuritis). Conclusions: In this large, clinical practice-based study, NMO-IgG detected by IF or IP was highly specific for NMO spectrum disorders. The IP assay was significantly less sensitive than IF. Combined testing improved sensitivity by 5{\%}.",
author = "McKeon, {Andrew B} and Fryer, {James P.} and Metha Apiwattanakul and Lennon, {Vanda A} and Hinson, {Shannon R.} and Kryzer, {Thomas J.} and Lucchinetti, {Claudia F} and Weinshenker, {Brian G} and Wingerchuk, {Dean Marko} and Shuster, {Elizabeth A.} and Pittock, {Sean J}",
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AU - McKeon, Andrew B

AU - Fryer, James P.

AU - Apiwattanakul, Metha

AU - Lennon, Vanda A

AU - Hinson, Shannon R.

AU - Kryzer, Thomas J.

AU - Lucchinetti, Claudia F

AU - Weinshenker, Brian G

AU - Wingerchuk, Dean Marko

AU - Shuster, Elizabeth A.

AU - Pittock, Sean J

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