Profile and Usefulness of Serum Cytokines to Predict Prognosis in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

Abstract

Objectives: To characterize the serum cytokine profile in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) at onset and during follow-up and assess their utility for predicting relapses and disability.

Methods: This retrospective multicentric cohort study included patients aged 16 years and older meeting MOGAD 2023 criteria, with serum samples collected at baseline (≤3 months from disease onset) and follow-up (≥6 months from the baseline), and age-matched and time to sampling-matched patients with multiple sclerosis (MS). Eleven cytokines were assessed using the ELLA system. Data comparisons and statistical analyses between cytokine levels and clinical outcomes were performed.

Results: Eighty-eight patients with MOGAD and 32 patients with MS were included. Patients with MOGAD showed higher IL6 (p = 0.036), IL8 (p = 0.012), and IL18 (p = 0.026) baseline levels compared with those with MS, in non-optic neuritis (ON) presentations. BAFF values increased over time, especially in patients with MOGAD treated with anti-CD20 (p = 0.002). Baseline BAFF, CXCL10, IL10, and IL8 levels correlated with disease severity at MOGAD onset (all p < 0.05). Finally, higher baseline BAFF levels predicted lower risk of relapses (hazard ratio 0.41 [0.19; 0.89], p = 0.024).

Discussion: This study suggests a proinflammatory Th17-dominant profile in non-ON MOGAD patients, with a novel finding of a potential protective role of BAFF on relapses. These results shed new light on the pathogenesis of MOGAD, potentially guiding therapeutic decisions.

Figure 1. Baseline Serum Cytokines Between Patients With MOGAD and MS With Non–Optic Neuritis Presentations

Boxplots depict the distribution of baseline serum log-transformed values of the 9 cytokines between patients with MOGAD and MS with non–optic neuritis presentations. Median values are represented by the horizontal bar, IQR by hinges, 1.5 × IQR by whiskers, and individual values by dots. p Values are represented by asterisks as follows: * <0.05. IQR = interquartile range; MOGAD = myelin oligodendrocyte glycoprotein antibody–associated disease; MS = multiple sclerosis.

Figure 2. BAFF Increases After Rituximab Treatment and Predicts Relapses During Follow-Up

Boxplots depict the distribution of serum BAFF log-transformed values between first and second samples in the 15 patients with MOGAD who received anti-CD20 therapy between both time points (A) and the distribution of serum BAFF log-transformed values in second samples between those patients under anti-CD20 treatment (N = 15) and the remaining patients (N = 73) at the time of second sampling (B). Median values are represented by the horizontal bar, IQR by hinges, 1.5 × IQR by whiskers, and individual values by dots joined by gray lines between time points. p Values are represented by asterisks as follows: ** <0.01. (C) The representation of the Kaplan-Meier curves for the time to first relapse between patients with high (≥5.71) and low (<5.71) baseline BAFF values in the MOGAD cohort. The cutoff 5.71 is the 25th percentile value of BAFF in the MOGAD cohort. *Note: five patients were excluded from the Kaplan-Meier and Cox analyses because their baseline samples were obtained after the first relapse. IQR = interquartile range; MOGAD = myelin oligodendrocyte glycoprotein antibody–associated disease.