Prediction of neuromyelitis optica attack severity by quantitation of complement-mediated injury to aquaporin-4 -expressing cells

Shannon R. Hinson, Andrew B McKeon, James P. Fryer, Metha Apiwattanakul, Vanda A Lennon, Sean J Pittock

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Background: Recent reports support a pathogenic role in neuromyelitis optica (NMO) for the aquaporin-4 (AQP4) - specific autoantibody (NMO-IgG). Neuromyelitis optica is an inflammatory demyelinating central nervous system disease, usually relapsing, that causes variable degrees of attack-related disability. The NMO-IgG binds in vitro to the extracellular domain of AQP4, activates complement, and causes astrocyte lesioning. Objective: To compare the prognostic utility of NMO-IgG titer and quantitative measures of complement-mediated injury to AQP4-expressing cells in NMO attacks. Design, Setting, and Participants: A retrospective clinical-serological correlative study at Mayo Clinic's Neuroimmunology Laboratory was undertaken. Over an 18-month period, we identified NMO-IgG - seropositive patients in whom sufficient serum and adequate clinical information pertaining to NMO attacks (6 severe, 6 mild) were available to analyze clinical-serological correlations. Sera from 9 patients with multiple sclerosis and 9 healthy subjects (all NMO-IgG seronegative) served as controls. Complement activation was measured by quantifying the number of green fluorescent protein - AQP4 - transfected HEK 293 cells permeable to the viability dye propidium iodide after exposure to patient serum and active complement. Main Outcome Measures: Attack severity (mild or severe), percentage of AQP4-transfected cells lesioned, and NMO-IgG titer. Results: The median percentage of AQP4-transfected cells lesioned by complement in the presence of serum from patients with NMO was 14% for patients with mild attacks and 54% for patients with severe attacks (P = .005). Median complement activation values for sera from healthy subjects and patients with multiple sclerosis were 8% and 12%, respectively. Patients with mild NMO attacks and patients with severe NMO attacks did not differ significantly with respect to NMO-IgG titer (P = .089). Conclusions: A laboratory measure of complement-mediated cell injury may serve as a prognostic biomarker in NMO. Larger prospective studies are required to validate this observation.

Original languageEnglish (US)
Pages (from-to)1164-1167
Number of pages4
JournalArchives of Neurology
Volume66
Issue number9
DOIs
StatePublished - Sep 2009

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Aquaporin 4
Neuromyelitis Optica
Wounds and Injuries
Immunoglobulin G
Serum
Complement Activation
Attack
Cells
Prediction
Multiple Sclerosis
Healthy Volunteers
Propidium
HEK293 Cells
Central Nervous System Diseases

ASJC Scopus subject areas

  • Clinical Neurology

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Prediction of neuromyelitis optica attack severity by quantitation of complement-mediated injury to aquaporin-4 -expressing cells. / Hinson, Shannon R.; McKeon, Andrew B; Fryer, James P.; Apiwattanakul, Metha; Lennon, Vanda A; Pittock, Sean J.

In: Archives of Neurology, Vol. 66, No. 9, 09.2009, p. 1164-1167.

Research output: Contribution to journalArticle

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abstract = "Background: Recent reports support a pathogenic role in neuromyelitis optica (NMO) for the aquaporin-4 (AQP4) - specific autoantibody (NMO-IgG). Neuromyelitis optica is an inflammatory demyelinating central nervous system disease, usually relapsing, that causes variable degrees of attack-related disability. The NMO-IgG binds in vitro to the extracellular domain of AQP4, activates complement, and causes astrocyte lesioning. Objective: To compare the prognostic utility of NMO-IgG titer and quantitative measures of complement-mediated injury to AQP4-expressing cells in NMO attacks. Design, Setting, and Participants: A retrospective clinical-serological correlative study at Mayo Clinic's Neuroimmunology Laboratory was undertaken. Over an 18-month period, we identified NMO-IgG - seropositive patients in whom sufficient serum and adequate clinical information pertaining to NMO attacks (6 severe, 6 mild) were available to analyze clinical-serological correlations. Sera from 9 patients with multiple sclerosis and 9 healthy subjects (all NMO-IgG seronegative) served as controls. Complement activation was measured by quantifying the number of green fluorescent protein - AQP4 - transfected HEK 293 cells permeable to the viability dye propidium iodide after exposure to patient serum and active complement. Main Outcome Measures: Attack severity (mild or severe), percentage of AQP4-transfected cells lesioned, and NMO-IgG titer. Results: The median percentage of AQP4-transfected cells lesioned by complement in the presence of serum from patients with NMO was 14{\%} for patients with mild attacks and 54{\%} for patients with severe attacks (P = .005). Median complement activation values for sera from healthy subjects and patients with multiple sclerosis were 8{\%} and 12{\%}, respectively. Patients with mild NMO attacks and patients with severe NMO attacks did not differ significantly with respect to NMO-IgG titer (P = .089). Conclusions: A laboratory measure of complement-mediated cell injury may serve as a prognostic biomarker in NMO. Larger prospective studies are required to validate this observation.",
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AU - Lennon, Vanda A

AU - Pittock, Sean J

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N2 - Background: Recent reports support a pathogenic role in neuromyelitis optica (NMO) for the aquaporin-4 (AQP4) - specific autoantibody (NMO-IgG). Neuromyelitis optica is an inflammatory demyelinating central nervous system disease, usually relapsing, that causes variable degrees of attack-related disability. The NMO-IgG binds in vitro to the extracellular domain of AQP4, activates complement, and causes astrocyte lesioning. Objective: To compare the prognostic utility of NMO-IgG titer and quantitative measures of complement-mediated injury to AQP4-expressing cells in NMO attacks. Design, Setting, and Participants: A retrospective clinical-serological correlative study at Mayo Clinic's Neuroimmunology Laboratory was undertaken. Over an 18-month period, we identified NMO-IgG - seropositive patients in whom sufficient serum and adequate clinical information pertaining to NMO attacks (6 severe, 6 mild) were available to analyze clinical-serological correlations. Sera from 9 patients with multiple sclerosis and 9 healthy subjects (all NMO-IgG seronegative) served as controls. Complement activation was measured by quantifying the number of green fluorescent protein - AQP4 - transfected HEK 293 cells permeable to the viability dye propidium iodide after exposure to patient serum and active complement. Main Outcome Measures: Attack severity (mild or severe), percentage of AQP4-transfected cells lesioned, and NMO-IgG titer. Results: The median percentage of AQP4-transfected cells lesioned by complement in the presence of serum from patients with NMO was 14% for patients with mild attacks and 54% for patients with severe attacks (P = .005). Median complement activation values for sera from healthy subjects and patients with multiple sclerosis were 8% and 12%, respectively. Patients with mild NMO attacks and patients with severe NMO attacks did not differ significantly with respect to NMO-IgG titer (P = .089). Conclusions: A laboratory measure of complement-mediated cell injury may serve as a prognostic biomarker in NMO. Larger prospective studies are required to validate this observation.

AB - Background: Recent reports support a pathogenic role in neuromyelitis optica (NMO) for the aquaporin-4 (AQP4) - specific autoantibody (NMO-IgG). Neuromyelitis optica is an inflammatory demyelinating central nervous system disease, usually relapsing, that causes variable degrees of attack-related disability. The NMO-IgG binds in vitro to the extracellular domain of AQP4, activates complement, and causes astrocyte lesioning. Objective: To compare the prognostic utility of NMO-IgG titer and quantitative measures of complement-mediated injury to AQP4-expressing cells in NMO attacks. Design, Setting, and Participants: A retrospective clinical-serological correlative study at Mayo Clinic's Neuroimmunology Laboratory was undertaken. Over an 18-month period, we identified NMO-IgG - seropositive patients in whom sufficient serum and adequate clinical information pertaining to NMO attacks (6 severe, 6 mild) were available to analyze clinical-serological correlations. Sera from 9 patients with multiple sclerosis and 9 healthy subjects (all NMO-IgG seronegative) served as controls. Complement activation was measured by quantifying the number of green fluorescent protein - AQP4 - transfected HEK 293 cells permeable to the viability dye propidium iodide after exposure to patient serum and active complement. Main Outcome Measures: Attack severity (mild or severe), percentage of AQP4-transfected cells lesioned, and NMO-IgG titer. Results: The median percentage of AQP4-transfected cells lesioned by complement in the presence of serum from patients with NMO was 14% for patients with mild attacks and 54% for patients with severe attacks (P = .005). Median complement activation values for sera from healthy subjects and patients with multiple sclerosis were 8% and 12%, respectively. Patients with mild NMO attacks and patients with severe NMO attacks did not differ significantly with respect to NMO-IgG titer (P = .089). Conclusions: A laboratory measure of complement-mediated cell injury may serve as a prognostic biomarker in NMO. Larger prospective studies are required to validate this observation.

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