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July 2020; 7 (4) ArticleOpen Access

Clinical utility of AQP4-IgG titers and measures of complement-mediated cell killing in NMOSD

View ORCID ProfileJiraporn Jitprapaikulsan, James P. Fryer, Masoud Majed, Carin Y. Smith, Sarah M. Jenkins, Philippe Cabre, Shannon R. Hinson, View ORCID ProfileBrian G. Weinshenker, Jay Mandrekar, John J. Chen, Claudia F. Lucchinetti, Yujuan Jiao, Jessica Segan, John E. Schmeling, John Mills, Eoin P. Flanagan, Andrew McKeon, Sean J. Pittock
First published May 28, 2020, DOI: https://doi.org/10.1212/NXI.0000000000000727
Jiraporn Jitprapaikulsan
From the Departments of Neurology (J.J., M.M., B.G.W., C.F.L., Y.J., E.P.F., A.M., S.J.P.), Laboratory Medicine and Pathology (J.J., J.P.F., S.R.H., J.E.S., J. Mills, A.M., S.J.P.), Health Sciences Research (C.Y.S., S.M.J., J. Mandrekar), Mayo Clinic, Rochester, MN; Department of Neurology (P.C.), Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Martinique; Center for MS and Autoimmune Neurology (B.G.W., J.J.C., C.F.L., J. S., J. Mills, E.P.F., A.M., S.J.P.), and Department of Ophthalmology (J.J.C.), Mayo Clinic, Rochester, MN.
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James P. Fryer
From the Departments of Neurology (J.J., M.M., B.G.W., C.F.L., Y.J., E.P.F., A.M., S.J.P.), Laboratory Medicine and Pathology (J.J., J.P.F., S.R.H., J.E.S., J. Mills, A.M., S.J.P.), Health Sciences Research (C.Y.S., S.M.J., J. Mandrekar), Mayo Clinic, Rochester, MN; Department of Neurology (P.C.), Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Martinique; Center for MS and Autoimmune Neurology (B.G.W., J.J.C., C.F.L., J. S., J. Mills, E.P.F., A.M., S.J.P.), and Department of Ophthalmology (J.J.C.), Mayo Clinic, Rochester, MN.
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Masoud Majed
From the Departments of Neurology (J.J., M.M., B.G.W., C.F.L., Y.J., E.P.F., A.M., S.J.P.), Laboratory Medicine and Pathology (J.J., J.P.F., S.R.H., J.E.S., J. Mills, A.M., S.J.P.), Health Sciences Research (C.Y.S., S.M.J., J. Mandrekar), Mayo Clinic, Rochester, MN; Department of Neurology (P.C.), Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Martinique; Center for MS and Autoimmune Neurology (B.G.W., J.J.C., C.F.L., J. S., J. Mills, E.P.F., A.M., S.J.P.), and Department of Ophthalmology (J.J.C.), Mayo Clinic, Rochester, MN.
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Carin Y. Smith
From the Departments of Neurology (J.J., M.M., B.G.W., C.F.L., Y.J., E.P.F., A.M., S.J.P.), Laboratory Medicine and Pathology (J.J., J.P.F., S.R.H., J.E.S., J. Mills, A.M., S.J.P.), Health Sciences Research (C.Y.S., S.M.J., J. Mandrekar), Mayo Clinic, Rochester, MN; Department of Neurology (P.C.), Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Martinique; Center for MS and Autoimmune Neurology (B.G.W., J.J.C., C.F.L., J. S., J. Mills, E.P.F., A.M., S.J.P.), and Department of Ophthalmology (J.J.C.), Mayo Clinic, Rochester, MN.
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Sarah M. Jenkins
From the Departments of Neurology (J.J., M.M., B.G.W., C.F.L., Y.J., E.P.F., A.M., S.J.P.), Laboratory Medicine and Pathology (J.J., J.P.F., S.R.H., J.E.S., J. Mills, A.M., S.J.P.), Health Sciences Research (C.Y.S., S.M.J., J. Mandrekar), Mayo Clinic, Rochester, MN; Department of Neurology (P.C.), Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Martinique; Center for MS and Autoimmune Neurology (B.G.W., J.J.C., C.F.L., J. S., J. Mills, E.P.F., A.M., S.J.P.), and Department of Ophthalmology (J.J.C.), Mayo Clinic, Rochester, MN.
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Philippe Cabre
From the Departments of Neurology (J.J., M.M., B.G.W., C.F.L., Y.J., E.P.F., A.M., S.J.P.), Laboratory Medicine and Pathology (J.J., J.P.F., S.R.H., J.E.S., J. Mills, A.M., S.J.P.), Health Sciences Research (C.Y.S., S.M.J., J. Mandrekar), Mayo Clinic, Rochester, MN; Department of Neurology (P.C.), Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Martinique; Center for MS and Autoimmune Neurology (B.G.W., J.J.C., C.F.L., J. S., J. Mills, E.P.F., A.M., S.J.P.), and Department of Ophthalmology (J.J.C.), Mayo Clinic, Rochester, MN.
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Shannon R. Hinson
From the Departments of Neurology (J.J., M.M., B.G.W., C.F.L., Y.J., E.P.F., A.M., S.J.P.), Laboratory Medicine and Pathology (J.J., J.P.F., S.R.H., J.E.S., J. Mills, A.M., S.J.P.), Health Sciences Research (C.Y.S., S.M.J., J. Mandrekar), Mayo Clinic, Rochester, MN; Department of Neurology (P.C.), Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Martinique; Center for MS and Autoimmune Neurology (B.G.W., J.J.C., C.F.L., J. S., J. Mills, E.P.F., A.M., S.J.P.), and Department of Ophthalmology (J.J.C.), Mayo Clinic, Rochester, MN.
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Brian G. Weinshenker
From the Departments of Neurology (J.J., M.M., B.G.W., C.F.L., Y.J., E.P.F., A.M., S.J.P.), Laboratory Medicine and Pathology (J.J., J.P.F., S.R.H., J.E.S., J. Mills, A.M., S.J.P.), Health Sciences Research (C.Y.S., S.M.J., J. Mandrekar), Mayo Clinic, Rochester, MN; Department of Neurology (P.C.), Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Martinique; Center for MS and Autoimmune Neurology (B.G.W., J.J.C., C.F.L., J. S., J. Mills, E.P.F., A.M., S.J.P.), and Department of Ophthalmology (J.J.C.), Mayo Clinic, Rochester, MN.
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Jay Mandrekar
From the Departments of Neurology (J.J., M.M., B.G.W., C.F.L., Y.J., E.P.F., A.M., S.J.P.), Laboratory Medicine and Pathology (J.J., J.P.F., S.R.H., J.E.S., J. Mills, A.M., S.J.P.), Health Sciences Research (C.Y.S., S.M.J., J. Mandrekar), Mayo Clinic, Rochester, MN; Department of Neurology (P.C.), Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Martinique; Center for MS and Autoimmune Neurology (B.G.W., J.J.C., C.F.L., J. S., J. Mills, E.P.F., A.M., S.J.P.), and Department of Ophthalmology (J.J.C.), Mayo Clinic, Rochester, MN.
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John J. Chen
From the Departments of Neurology (J.J., M.M., B.G.W., C.F.L., Y.J., E.P.F., A.M., S.J.P.), Laboratory Medicine and Pathology (J.J., J.P.F., S.R.H., J.E.S., J. Mills, A.M., S.J.P.), Health Sciences Research (C.Y.S., S.M.J., J. Mandrekar), Mayo Clinic, Rochester, MN; Department of Neurology (P.C.), Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Martinique; Center for MS and Autoimmune Neurology (B.G.W., J.J.C., C.F.L., J. S., J. Mills, E.P.F., A.M., S.J.P.), and Department of Ophthalmology (J.J.C.), Mayo Clinic, Rochester, MN.
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Claudia F. Lucchinetti
From the Departments of Neurology (J.J., M.M., B.G.W., C.F.L., Y.J., E.P.F., A.M., S.J.P.), Laboratory Medicine and Pathology (J.J., J.P.F., S.R.H., J.E.S., J. Mills, A.M., S.J.P.), Health Sciences Research (C.Y.S., S.M.J., J. Mandrekar), Mayo Clinic, Rochester, MN; Department of Neurology (P.C.), Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Martinique; Center for MS and Autoimmune Neurology (B.G.W., J.J.C., C.F.L., J. S., J. Mills, E.P.F., A.M., S.J.P.), and Department of Ophthalmology (J.J.C.), Mayo Clinic, Rochester, MN.
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Yujuan Jiao
From the Departments of Neurology (J.J., M.M., B.G.W., C.F.L., Y.J., E.P.F., A.M., S.J.P.), Laboratory Medicine and Pathology (J.J., J.P.F., S.R.H., J.E.S., J. Mills, A.M., S.J.P.), Health Sciences Research (C.Y.S., S.M.J., J. Mandrekar), Mayo Clinic, Rochester, MN; Department of Neurology (P.C.), Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Martinique; Center for MS and Autoimmune Neurology (B.G.W., J.J.C., C.F.L., J. S., J. Mills, E.P.F., A.M., S.J.P.), and Department of Ophthalmology (J.J.C.), Mayo Clinic, Rochester, MN.
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Jessica Segan
From the Departments of Neurology (J.J., M.M., B.G.W., C.F.L., Y.J., E.P.F., A.M., S.J.P.), Laboratory Medicine and Pathology (J.J., J.P.F., S.R.H., J.E.S., J. Mills, A.M., S.J.P.), Health Sciences Research (C.Y.S., S.M.J., J. Mandrekar), Mayo Clinic, Rochester, MN; Department of Neurology (P.C.), Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Martinique; Center for MS and Autoimmune Neurology (B.G.W., J.J.C., C.F.L., J. S., J. Mills, E.P.F., A.M., S.J.P.), and Department of Ophthalmology (J.J.C.), Mayo Clinic, Rochester, MN.
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John E. Schmeling
From the Departments of Neurology (J.J., M.M., B.G.W., C.F.L., Y.J., E.P.F., A.M., S.J.P.), Laboratory Medicine and Pathology (J.J., J.P.F., S.R.H., J.E.S., J. Mills, A.M., S.J.P.), Health Sciences Research (C.Y.S., S.M.J., J. Mandrekar), Mayo Clinic, Rochester, MN; Department of Neurology (P.C.), Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Martinique; Center for MS and Autoimmune Neurology (B.G.W., J.J.C., C.F.L., J. S., J. Mills, E.P.F., A.M., S.J.P.), and Department of Ophthalmology (J.J.C.), Mayo Clinic, Rochester, MN.
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John Mills
From the Departments of Neurology (J.J., M.M., B.G.W., C.F.L., Y.J., E.P.F., A.M., S.J.P.), Laboratory Medicine and Pathology (J.J., J.P.F., S.R.H., J.E.S., J. Mills, A.M., S.J.P.), Health Sciences Research (C.Y.S., S.M.J., J. Mandrekar), Mayo Clinic, Rochester, MN; Department of Neurology (P.C.), Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Martinique; Center for MS and Autoimmune Neurology (B.G.W., J.J.C., C.F.L., J. S., J. Mills, E.P.F., A.M., S.J.P.), and Department of Ophthalmology (J.J.C.), Mayo Clinic, Rochester, MN.
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Eoin P. Flanagan
From the Departments of Neurology (J.J., M.M., B.G.W., C.F.L., Y.J., E.P.F., A.M., S.J.P.), Laboratory Medicine and Pathology (J.J., J.P.F., S.R.H., J.E.S., J. Mills, A.M., S.J.P.), Health Sciences Research (C.Y.S., S.M.J., J. Mandrekar), Mayo Clinic, Rochester, MN; Department of Neurology (P.C.), Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Martinique; Center for MS and Autoimmune Neurology (B.G.W., J.J.C., C.F.L., J. S., J. Mills, E.P.F., A.M., S.J.P.), and Department of Ophthalmology (J.J.C.), Mayo Clinic, Rochester, MN.
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Andrew McKeon
From the Departments of Neurology (J.J., M.M., B.G.W., C.F.L., Y.J., E.P.F., A.M., S.J.P.), Laboratory Medicine and Pathology (J.J., J.P.F., S.R.H., J.E.S., J. Mills, A.M., S.J.P.), Health Sciences Research (C.Y.S., S.M.J., J. Mandrekar), Mayo Clinic, Rochester, MN; Department of Neurology (P.C.), Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Martinique; Center for MS and Autoimmune Neurology (B.G.W., J.J.C., C.F.L., J. S., J. Mills, E.P.F., A.M., S.J.P.), and Department of Ophthalmology (J.J.C.), Mayo Clinic, Rochester, MN.
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Sean J. Pittock
From the Departments of Neurology (J.J., M.M., B.G.W., C.F.L., Y.J., E.P.F., A.M., S.J.P.), Laboratory Medicine and Pathology (J.J., J.P.F., S.R.H., J.E.S., J. Mills, A.M., S.J.P.), Health Sciences Research (C.Y.S., S.M.J., J. Mandrekar), Mayo Clinic, Rochester, MN; Department of Neurology (P.C.), Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Martinique; Center for MS and Autoimmune Neurology (B.G.W., J.J.C., C.F.L., J. S., J. Mills, E.P.F., A.M., S.J.P.), and Department of Ophthalmology (J.J.C.), Mayo Clinic, Rochester, MN.
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Full PDF
Citation
Clinical utility of AQP4-IgG titers and measures of complement-mediated cell killing in NMOSD
Jiraporn Jitprapaikulsan, James P. Fryer, Masoud Majed, Carin Y. Smith, Sarah M. Jenkins, Philippe Cabre, Shannon R. Hinson, Brian G. Weinshenker, Jay Mandrekar, John J. Chen, Claudia F. Lucchinetti, Yujuan Jiao, Jessica Segan, John E. Schmeling, John Mills, Eoin P. Flanagan, Andrew McKeon, Sean J. Pittock
Neurol Neuroimmunol Neuroinflamm Jul 2020, 7 (4) e727; DOI: 10.1212/NXI.0000000000000727

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    Figure 1 AQP4-IgG (binding and complement-mediated cell killing) titers of specimens drawn at different time points (remission, preattack, and attack) in individual patients (original titer values shown in transformed scale)

    (A.a) AQP4-IgG titers grouped into preattack, attack, and remission categories. (B.a) AQP4-IgG titers categorized according to baseline immunotherapy*. (C.a) AQP4-IgG titers categorized by attack severity type**. (A.b) AQP4 complement-mediated cell killing titers grouped into preattack, attack, and remission categories. (B.b) AQP4 complement-mediated cell killing titers categorized according to baseline immunotherapy*. (C.b) AQP4 complement-mediated cell killing titers categorized grouped into attack severity type**. *Immunotherapy included azathioprine, mycophenolate mofetil, cyclophosphamide, and rituximab. **Definition in the supplement. AQP4 = aquaporin-4; IgG = immunoglobulin G; IST = immunosuppressive therapy.

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    Figure 2 Kaplan-Meier estimates of time to develop EDSS score ≥ 6

    Years from the first aquaporin-4–immunoglobulin G complement-mediated cell killing titers to develop EDSS score ≥6. All Martinique patients, any patients with unknown status for each outcome, and any patients with missing complement values were excluded from the corresponding analysis. EDSS = Expanded Disability Status Scale.

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    Figure 3 Correlation between M23-AQP4 end titer and M23-AQP4 complement-mediated cell killing titers

    AQP4 = aquaporin-4; IgG = immunoglobulin G.

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  • links.lww.com/NXI/A254
  • links.lww.com/NXI/A255
  • links.lww.com/NXI/A257
  • links.lww.com/NXI/A256
  • Neurology.org/NN
  • Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND)
  • doi: 10.1212/NXI.0000000000000011
  • doi: 10.1212/NXI.0000000000000121
  • doi: 10.1212/NXI.0000000000000231

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