Temporal Dynamics of MOG Antibodies in Children With Acquired Demyelinating Syndrome

Abstract

Background and objective: The spectrum of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorder (MOGAD) comprises monophasic diseases such as acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), and transverse myelitis and relapsing courses of these presentations. Persistently high MOG antibodies (MOG immunoglobulin G [IgG]) are found in patients with a relapsing disease course. Prognostic factors to determine the clinical course of children with a first MOGAD are still lacking. The objective of the study is to assess the clinical and laboratory prognostic parameters for a risk of relapse and the temporal dynamics of MOG-IgG titers in children with MOGAD in correlation with clinical presentation and disease course.

Methods: In this prospective multicenter hospital-based study, children with a first demyelinating attack and complete data set comprising clinical and radiologic findings, MOG-IgG titer at onset, and clinical and serologic follow-up data were included. Serum samples were analyzed by live cell-based assay, and a titer level of ≥1:160 was classified as MOG-IgG-positive.

Results: One hundred sixteen children (f:m = 57:59) with MOGAD were included and initially diagnosed with ADEM (n = 59), unilateral ON (n = 12), bilateral ON (n = 16), myelitis (n = 6), neuromyelitis optica spectrum disorder (n = 8) or encephalitis (n = 6). The median follow-up time was 3 years in monophasic and 5 years in relapsing patients. There was no significant association between disease course and MOG-IgG titers at onset, sex, age at presentation, or clinical phenotype. Seroconversion to MOG-IgG-negative within 2 years of the initial event showed a significant risk reduction for a relapsing disease course. Forty-two/one hundred sixteen patients (monophasic n = 26, relapsing n = 16) had serial MOG-IgG testing in years 1 and 2 after the initial event. In contrast to relapsing patients, monophasic patients showed a significant decrease of MOG-IgG titers during the first and second years, often with seroconversion to negative titers. During the follow-up, MOG-IgG titers were persistently higher in relapsing than in monophasic patients. Decrease in MOG-IgG of ≥3 dilution steps after the first and second years was shown to be associated with a decreased risk of relapses. In our cohort, no patient experienced a relapse after seroconversion to MOG-IgG-negative.

Discussion: In this study, patients with declining MOG-IgG titers, particularly those with seroconversion to MOG-IgG-negative, are shown to have a significantly reduced relapse risk.

Figure 1. MOG-IgG–Positive Pediatric Patients With Clinical Presentation at the First Event and After at Least 24 Months

116/155 MOG-IgG–positive pediatric patients were included in the study. Fifty-nine patients presented with ADEM, 21 patients with unilateral ON, 16 patients with bilateral ON, 6 patients with myelitis, 8 patients with NMOSD, and 6 patients with encephalitis. After at least 24 months of a clinical follow-up, further relapses have occurred in 24 patients with ADEM, 12 patients with unilateral ON, 2 patients with bilateral ON, 1 patient with myelitis, 2 patients with NMOSD, and 3 patients with encephalitis. Thirty-nine/155 patients had to be excluded because of the following reasons: no available serum sample from disease onset (n = 7), insufficient clinical (n = 2) or serologic (n = 26) follow-up data, or a final diagnosis of MS (n = 4). ADEM = acute disseminated encephalomyelitis; IgG = immunoglobulin G; MOG = myelin oligodendrocyte glycoprotein; NMOSD = neuromyelitis optica spectrum disorder; ON = optic neuritis.

Figure 2. Comparison of MOG-IgG Titers During Disease Course Between Monophasic and Relapsing Pediatric Patients

Comparison of MOG-IgG titers between monophasic (n = 26) and relapsing (n = 16) pediatric patients in children with serial follow-up in years 1 (months 6–12) and 2 (months 18–24) after onset. MOG-IgG titers show a statistically significant decrease during the first and second years in monophasic patients (A, overall p < 0.001), in contrast to a lower decline during the first and second years in relapsing patients (B, overall p = 0.05). Individual data points in A and B are shown as dots and medians as bars. Groups were statistically compared using the Friedman test and Dunn multiple comparison tests. ***Significant difference to onset at p < 0.001, ns = statistically not significant. IgG = immunoglobulin G; MOG = myelin oligodendrocyte glycoprotein.