What proportion of AQP4-IgG-negative NMO spectrum disorder patients are MOG-IgG positive? A cross sectional study of 132 patients

Abstract

Antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) have been described in patients with neuromyelitis optica spectrum disorders (NMOSD) without aquaporin-4 antibodies (AQP4-IgG). We aimed to identify the proportion of AQP4-IgG-negative NMOSD patients who are seropositive for MOG-IgG. In a cross sectional study, we reviewed all patients seen in the National NMO clinic over the last 4 years (after the availability of MOG-IgG testing), including clinical information, MRI, and antibody tests. 261 unique patients were identified. 132 cases satisfied the 2015 NMOSD diagnostic criteria. Of these, 96 (73%) were AQP4-IgG positive and 36 (27%) were AQP4-IgG negative. These 36 patients were tested for MOG-IgG and 15/36 (42%) tested positive. 20% (25/125) of the patients who did not satisfy NMOSD criteria had MOG-IgG. Approximately half of seronegative NMOSD is MOG-Ig seropositive and one in five of non-NMOSD/non-MS demyelination is MOG-IgG positive. Since MOG-associated demyelinating disease is likely different from AQP4-IgG disease in terms of underlying disease mechanisms, relapse risk and possibly treatment, testing for MOG-IgG in patients with AQP4-IgG-negative NMOSD and other non-MS demyelination may have significant implications to management and clinical trials.

Review: Recent advances in the understanding of the pathophysiology of neuromyelitis optica spectrum disorder

“…Clinical studies investigating the role of MOG‐IgG in the pathogenesis of NMOSD are still emerging. Using highly sensitive cell‐based assays (CBAs), approximately 15–40% of patients with AQP4‐IgG‐seronegative NMOSD tested positive for MOG‐IgG, accounting for 6–20% of the total cohort of patients with NMOSD . Interestingly, patients with NMOSD who were seropositive for both antibodies (both AQP4‐IgG and MOG‐IgG) are rare, and only sporadic cases have been reported .…”

Magnetic resonance imaging diagnosis of demyelinating diseases: An update

“…45 Whether acute hemorrhagic leukoencephalitis is a variant of ADEM or separate entity remains controversial. [97][98][99] MOG-IgG positivity is found in patients who have previously been diagnosed with a variety of clinical phenotypes, such as ADEM, MS, optic neuritis and transverse myelitis. 22,59,91 Gadolinium enhancement is variable.…”

“…It has been reported that 21-42% of AQP4-IgG-negative NMOSD patients are MOG-IgG-positive. [97][98][99] MOG-IgG positivity is found in patients who have previously been diagnosed with a variety of clinical phenotypes, such as ADEM, MS, optic neuritis and transverse myelitis. 92,98,100,101 A significant percentage of patients previously diagnosed with multiphasic demyelinating encephalomyelitis and ADEM followed by optic neuritis are also MOG-IgG-positive.…”

Eculizumab: A Review in Neuromyelitis Optica Spectrum Disorder

“…Previously considered a variant of multiple sclerosis, recognition of NMOSD as a separate clinical entity and its differential diagnosis was revolutionized by the discovery of a disease-specific, pathogenic immunoglobulin G (IgG) autoantibody directed against the aquaporin-4 water channel (AQP4) in the serum of ≈ 75-90% of patients. Detection of AQP4-IgG greatly facilitates accurate identification of new cases (less stringent diagnostic criteria apply in AQP4-IgG-seropositive patients) and prompt initiation of treatment [1,4,[7][8][9]. Interestingly, a sizeable minority of APQ4-IgG seronegative patients presenting with symptoms of NMOSD display an autoantibody against myelin oligodendrocyte glycoprotein (MOG); increasingly, MOG-IgG is being regarded as a potentially pathogenic biomarker for a similar, but separate, disease entity (anti-MOG syndrome), rather than for a subgroup of NMOSD patients [1,3,10].…”