Early Immunotherapy and Longer Corticosteroid Treatment Are Associated With Lower Risk of Relapsing Disease Course in Pediatric MOGAD

Background and Objectives We sought to identify early factors associated with relapse and outcome in paediatric-onset myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD). Methods In a multicenter retrospective cohort of pediatric MOGAD (≤18 years), onset features and treatment were compared in patients with monophasic vs relapsing disease (including cases with follow-up ≥12 months after onset or relapse at any time) and in patients with final Expanded Disability Status Scale (EDSS) 0 vs ≥1 at last follow-up (including cases with followup >3 months after last event or EDSS0 at any time). Multivariable logistic regression models were used to evaluate factors associated with relapsing disease course and EDSS ≥ 1 at final follow-up. Results Seventy-five children were included (median onset age 7 years; median 30 months of follow-up). Presentation with acute disseminated encephalomyelitis was more frequent in children aged 8 years or younger (66.7%, 28/42) than in older patients (30.3%, 10/33) (p = 0.002), whereas presentation with optic neuritis was more common in children older than 8 years (57.6%, 19/33) than in younger patients (21.4%, 9/42) (p = 0.001). 40.0% (26/65) of patients relapsed. Time to first relapse was longer in children aged 8 years or younger than in older patients (median 18 vs 4 months) (p = 0.013). Factors at first event independently associated with lower risk of relapsing disease course were immunotherapy <7 days from onset (6.7-fold reduced odds of relapsing course, OR 0.15, 95% CI 0.03–0.61, p = 0.009), corticosteroid treatment for ≥5 weeks (6.7-fold reduced odds of relapse, OR 0.15, 95% CI 0.03–0.80, p = 0.026), and abnormal optic nerves on onset MRI (12.5-fold reduced odds of relapse, OR 0.08, 95% CI 0.01–0.50, p = 0.007). 21.1% (15/71) had EDSS ≥ 1 at final follow-up. Patients with a relapsing course had a higher proportion of final EDSS ≥ 1 (37.5%, 9/24) than children with monophasic disease (12.8%, 5/39) (p = 0.022, univariate analysis). Each 1-point increment in worst EDSS at onset was independently associated with 6.7-fold increased odds of final EDSS ≥ 1 (OR 6.65, 95% CI 1.33–33.26, p = 0.021). Discussion At first attack of pediatric MOGAD, early immunotherapy, longer duration of corticosteroid treatment, and abnormal optic nerves on MRI seem associated with lower risk of relapse, whereas higher disease severity is associated with greater risk of final disability (EDSS ≥ 1)

Exploring geographic differences in IgE response through network and manifold analyses

BACKGROUND: Component-resolved diagnostics allow detailed assessment of IgE sensitization to multiple allergenic molecules (component-specific IgEs, or c-sIgEs) and may be useful for asthma diagnosis. However, to effectively use component-resolved diagnostics across diverse settings, it is crucial to account for geographic differences. OBJECTIVE: We investigated spatial determinants of c-sIgE networks to facilitate development of diagnostic algorithms applicable globally. METHODS: We used multiplex component-resolved diagnostics array to measure c-sIgE to 112 proteins in an international collaboration of several studies: WASP (World Asthma Phenotypes; United Kingdom, New Zealand, Brazil, Ecuador, and Uganda), U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes; 7 European countries), and MAAS (Manchester Asthma and Allergy Study, a UK population-based birth cohort). Hierarchical clustering on low-dimensional representation of co-occurrence networks ascertained sensitization and c-sigE clusters across populations. Cross-country comparisons focused on a common subset of 18 c-sIgEs. We investigated sensitization networks across regions in relation to asthma severity. RESULTS: Sensitization profiles shared similarities across regions. For 18 c-sIgEs shared across study populations, the response structure enabled differentiation between different geographic areas and study designs, revealing 3 clusters: (1) Uganda, Ecuador, and Brazil, (2) U-BIOPRED children and adults, and (3) New Zealand, United Kingdom, and MAAS. Spectral clustering identified differences between clusters. We observed constant, almost parallel shifts between severe and nonsevere asthma in each country. CONCLUSIONS: Patterns of c-sIgE response reflect geographic location and study design. However, despite geographic differences in c-sIgE networks, there is a remarkably consistent shift between networks of subjects with nonsevere and severe asthma