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

doi:10.1212/NXI.0000000000000727

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

Neurol Neuroimmunol Neuroinflamm. 2020 May 28;7(4):e727. doi: 10.1212/NXI.0000000000000727. Print 2020 Jul.

Authors

Jiraporn Jitprapaikulsan¹, James P Fryer¹, Masoud Majed¹, Carin Y Smith¹, Sarah M Jenkins¹, Philippe Cabre¹, Shannon R Hinson¹, Brian G Weinshenker¹, Jay Mandrekar¹, John J Chen¹, Claudia F Lucchinetti¹, Yujuan Jiao¹, Jessica Segan¹, John E Schmeling¹, John Mills¹, Eoin P Flanagan¹, Andrew McKeon¹, Sean J Pittock²

Affiliations

¹ 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.
² 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. pittock.sean@mayo.edu.

Abstract

Objective: To investigate whether aquaporin-4-immunoglobulin G (AQP4-IgG) titers and measures of complement-mediated cell killing are clinically useful to predict the occurrence of relapse, relapse severity, and/or disability in neuromyelitis optica spectrum disorder (NMOSD).

Methods: We studied 336 serial serum specimens from 82 AQP4-lgG-seropositive patients. NMOSD activity at blood draw was defined as preattack (24 [7.1%], drawn within 30 days preceding an attack), attack (108 [32.1%], drawn on attack onset or within 30 days after), or remission (199 [59.2%], drawn >90 days after attack onset and >30 days preceding a relapse). For each specimen, we documented the attack type and severity and immunotherapy status. Complement-mediated cell killing was quantitated by flow cytometry using an M23-AQP4 cell-based assay.

Results: The estimated logarithmic means of AQP4-IgG titers in preattack, attack, and remission samples were 3.302, 3.657, and 3.458, respectively, p = 0.21. Analyses of 81 attack/remission pairs in 42 patients showed no significant titer differences (3.736 vs 3.472, p = 0.15). Analyses of 13 preattack/attack pairs in 9 patients showed no significant titer differences (3.994 vs 3.889, p = 0.67). Of 5 patients who converted to seronegative status, 2 continued to have attacks. Titers for major and minor attacks (n = 70) were not significantly different (3.905 vs 3.676, p = 0.47). Similarly, measures (titers) of complement-mediated cell killing were not significantly associated with disease course, attack severity, or disability at 5 years.

Conclusions and relevance: AQP4-IgG titer and complement-mediated cell killing lack significant prognostic or predictive utility in NMOSD. Although titers may drop in the setting of immunotherapy, seroconversion to negative status does not preclude ongoing clinical attacks.

Classification of evidence: This study provides Class II evidence that in patients with NMOSD, AQP4-IgG titers and measures of complement-mediated cell killing activity do not predict relapses, relapse severity, or disability.

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