The Mayo Clinic Glial Autoimmunity Study: Glial autoantibody (AQP4/MOG/GFAP) serostatus in recurrent longitudinally extensive transverse myelitis (P6.409)

Objective: To determine glial autoantibody serostatus in rLETM patients. Background: Autoimmune AQP-4 channelopathy is the commonest cause of immune-mediated recurrent longitudinally extensive transverse myelitis (rLETM). In 2014, our group reported AQP4-IgG detection in 89% rLETM cases [JAMA Neurol 2014]. Autoimmune myelin oligodendrocyte glycoproteinopathy (MOG-opathy) has recently been reported in AQP4-IgG seronegative LETM. The frequency of MOG-IgG1 antibodies in rLETM is unknown. The autoimmune GFAP astrocytopathy phenotype may include myelitis as a component of encephalomyelitis. Design/Methods: Patients (identified at Mayo Clinic 2005–2017) fulfilling the following criteria were included: 1) initial 2 attacks LETM, 2) serum available (for at least 1 glial antibody test), 3) alternative etiologies (e.g. infectious, rheumatologic, neoplastic, vascular) excluded. AQP4-IgG and MOG-IgG1 serostatus was determined using a validated flow cytometry assay utilizing live M1-AQP4-transfected and full length MOG-transfected HEK293 cells. GFAP-IgG serostatus was determined using indirect immunofluorescence assay. Results: AQP4-IgG was detected in 56/63 (89%) patients with rLETM. Serum was available on 58 of 63 rLETM patients for MOG-IgG1 testing: only 1 patient tested positive for MOG-IgG1 (subsequently developed optic neuritis). None (including 13 cerebrospinal fluid samples) tested positive for GFAP-IgG. Thus overall, AQP4-IgG+, MOG-IgG1+ and double negative (DN) groups accounted for 89%, 1.7% and 9% respectively (AQP4-IgG vs MOG-IgG1+/DN, p Conclusions: Accepting potential confounding by referral bias, autoimmune AQP4 channelopathy is the etiology of almost half of single LETM and almost 90% of rLETM. Autoimmune MOG-opathy can present with LETM, but recurrent sequential LETM is rarely associated with this condition. Inflammation, mainly restricted to spinal cord, as in these LETM cases is likely not within the Autoimmune GFAP astrocytopathy spectrum. Disclosure: Dr. Jitprapaikulsan has nothing to disclose. Dr. Lopez has nothing to disclose. Dr Flanagan has nothing to disclose. Dr. Fryer has nothing to disclose. Dr. McKeon has received research support from Medimmune, Euroimmun, Grifols and Alexion. Dr. Yujuan has nothing to disclose. Dr. Weinshenker has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis, Alexion, MedImmune, Caladrius Biosciences, Brainstorm Therapeutics. Dr. Majed has nothing to disclose. Dr. Tobin has nothing to disclose. Dr. Keegan has nothing to disclose. Dr. Lucchinetti has nothing to disclose. Dr. Lennon has received royalty, license fees, or contractual rights payments from RSR, royalties from sale kits for AQP4 IgG detetction and from clinical service assays performed outside Mayo clinic. Dr. Sagen has nothing to disclose. Dr. Pittock has nothing to disclose.