TY - JOUR
T1 - Aquaporin-4 and MOG autoantibody discovery in idiopathic transverse myelitis epidemiology
AU - Sechi, Elia
AU - Shosha, Eslam
AU - Williams, Jonathan P.
AU - Pittock, Sean J.
AU - Weinshenker, Brian G.
AU - Keegan, B. Mark
AU - Zalewski, Nicholas L.
AU - Lopez-Chiriboga, Alfonso Sebastian
AU - Jitprapaikulsan, Jiraporn
AU - Flanagan, Eoin P.
N1 - Funding Information:
This study was supported by a research fellowship funded by the Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology. This study was made possible with the resources of the Rochester Epidemiology Project, which is supported by the National Institute on Aging of the NIH under award R01AG034676. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Funding Information:
E. Sechi, E. Shosha, and J. Williams report no disclosures relevant to the manuscript. S. Pittock has financial interest in patents (12/678,350 filed in 2010 and 12/573,942 filed in 2008) that relate to functional AQP4/neuromyelitis optica (NMO)–IgG assays and NMO-IgG as a cancer marker. He has served as a consultant to Alexion Pharmaceuticals and MedImmune. He has received research funding from Alex-ion, MedImmune, and Grifols. B. Weinshenker receives royalties from RSR Ltd, Oxford University, Hospices Civil de Lyon, and MVZ Labor PD Dr. Volkmann und Kollegen GbR for a patent of NMO-IgG as a diagnostic test for NMO and related disorders. He serves as a member of an adjudication committee for clinical trials in NMO being conducted by Viela Bio and Alexion Pharmaceutical. He is a consultant for Caladrius Biosciences, Brainstorm Therapeutics, Roivant Sciences, and Chugai Pharma regarding potential clinical trials for NMO. B. Keegan was funded by Biogen and receives publishing royalties for Common Pitfalls in Multiple Sclerosis and CNS Demyelinating Diseases. He is an Editorial Board member of Multiple Sclerosis and Related Disorders. N. Zalewski, A. Lopez-Chiriboga, and J. Jitprapaikulsan report no disclosures relevant to the manuscript. E. Flanagan receives research support as a site principal investigator in a randomized placebo-controlled clinical trial of inebilizumab (A CD19 inhibitor) in NMO spectrum disorders funded by MedImmune/Viela Bio. Go to Neurology.org/N for full disclosures.
Publisher Copyright:
© American Academy of Neurology.
PY - 2019/7/23
Y1 - 2019/7/23
N2 - ObjectiveDiagnostic criteria from 2002 classify transverse myelitis (TM) as idiopathic or disease associated but predate the discovery of aquaporin-4 (AQP4)-immunoglobulin G (IgG) and myelin oligodendrocyte glycoprotein (MOG)-IgG, which associate with TM. Prior incidence estimates of idiopathic TM (ITM) range from 1 to 6.2 per 1 million. We sought to determine whether the population-based incidence and prevalence of ITM were reduced by testing patients with ITM for AQP4/MOG-IgG and reclassifying seropositive cases as having disease-associated TM.MethodsFor this observational study, we retrospectively identified all cases of incident (January 1, 2003-December 31, 2016) and prevalent (December 31, 2016) ITM in Olmsted County (85% white) by using the Rochester Epidemiology Project medical records linkage system. ITM was defined by the 2002 Transverse MyelitisConsortium Working Group diagnostic criteria. Available sera were tested for AQP4-IgG and MOG-IgG.ResultsTwenty-four patients (incident 22, prevalent 17) initially met 2002 ITM criteria (longitudinally extensive TM [LETM] 6). Sera were tested for AQP4-IgG in 22 of 24 (92%) and MOG-IgG in 21 of 24 (88%). Three seropositive cases (AQP4-IgG 2, MOG-IgG 1) were identified and reclassified as having disease-associated TM, accounting for 14% of total incident and 12% of total prevalent cases. AQP4-IgG and MOG-IgG seropositive cases represented 50% (3 of 6) of idiopathic LETM. After reclassification of seropositive patients, the final ITM incidence was 8.6 per 1,000,000 and prevalence was 7.9 per 100,000. Three cases of ITM (14%) subsequently fulfilled multiple sclerosis criteria within the study period.ConclusionsThe availability of AQP4-IgG and MOG-IgG modestly reduced ITM incidence and prevalence, which remained higher than previously reported in this predominantly white population. Incorporation of these biomarkers into future revisions of TM diagnostic criteria should be considered.
AB - ObjectiveDiagnostic criteria from 2002 classify transverse myelitis (TM) as idiopathic or disease associated but predate the discovery of aquaporin-4 (AQP4)-immunoglobulin G (IgG) and myelin oligodendrocyte glycoprotein (MOG)-IgG, which associate with TM. Prior incidence estimates of idiopathic TM (ITM) range from 1 to 6.2 per 1 million. We sought to determine whether the population-based incidence and prevalence of ITM were reduced by testing patients with ITM for AQP4/MOG-IgG and reclassifying seropositive cases as having disease-associated TM.MethodsFor this observational study, we retrospectively identified all cases of incident (January 1, 2003-December 31, 2016) and prevalent (December 31, 2016) ITM in Olmsted County (85% white) by using the Rochester Epidemiology Project medical records linkage system. ITM was defined by the 2002 Transverse MyelitisConsortium Working Group diagnostic criteria. Available sera were tested for AQP4-IgG and MOG-IgG.ResultsTwenty-four patients (incident 22, prevalent 17) initially met 2002 ITM criteria (longitudinally extensive TM [LETM] 6). Sera were tested for AQP4-IgG in 22 of 24 (92%) and MOG-IgG in 21 of 24 (88%). Three seropositive cases (AQP4-IgG 2, MOG-IgG 1) were identified and reclassified as having disease-associated TM, accounting for 14% of total incident and 12% of total prevalent cases. AQP4-IgG and MOG-IgG seropositive cases represented 50% (3 of 6) of idiopathic LETM. After reclassification of seropositive patients, the final ITM incidence was 8.6 per 1,000,000 and prevalence was 7.9 per 100,000. Three cases of ITM (14%) subsequently fulfilled multiple sclerosis criteria within the study period.ConclusionsThe availability of AQP4-IgG and MOG-IgG modestly reduced ITM incidence and prevalence, which remained higher than previously reported in this predominantly white population. Incorporation of these biomarkers into future revisions of TM diagnostic criteria should be considered.
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U2 - 10.1212/WNL.0000000000007828
DO - 10.1212/WNL.0000000000007828
M3 - Article
C2 - 31235660
AN - SCOPUS:85070183198
SN - 0028-3878
VL - 93
SP - E414-E420
JO - Neurology
JF - Neurology
IS - 4
ER -