University of Utah, George E. Wahlen Department of Veterans Affairs Medical Center

Author Of 1 Presentation

Pediatric MS Oral Presentation

PS04.04 - Evidence for an interaction between ozone pollution and HLA-DRB1*15 alleles in pediatric multiple sclerosis

Abstract

Background

We previously reported a relationship between air pollutants and increased risk of pediatric MS (ped-MS). Environmental risk factor research in ped-MS offers the advantage of shorter duration between exposure and disease onset. Ozone, an air pollutant, is a major global health hazard thought to have a role in MS pathoetiology. Identifying gene-environment interactions advances the understanding of biological processes at play in MS susceptibility.

Objectives

We sought to examine the interaction between ozone pollution and DRB1*15 status as the main genetic variant associated with MS susceptibility.

Methods

Cases and controls enrolled in the Environmental and Genetic Risk Factors for Pediatric MS study of the US Network of Pediatric MS Centers were analysed. County-level modeled ozone data were acquired from the CDC’s Environmental Tracking Network air pollution database. Participants were assigned ozone values based on county of residence. Values were categorized into tertiles based on healthy controls. The association between ozone tertiles and having MS were assessed by logistic regression. Interaction between tertiles of ozone level and presence of DRB1*15 alleles on odds of ped-MS was evaluated. Models were adjusted for sex, race, ethnicity, age, second-hand smoke exposure, and mother’s education. Additive interaction was estimated using relative risk due to interaction (RERI) and attributable proportion of disease were calculated.

Results

355 ped-MS cases and 565 controls contributed to the analyses. Ozone levels were associated with MS with an odds ratio (OR) of 2.35 (95%CI 1.57–3.51) and 2.21 (95%CI 1.48–3.32) in the upper two tertiles, respectively, compared with the lowest tertile. DRB1 status was also independently associated with MS (OR 1.99; 95%CI 1.43–2.78). There was a significant additive interaction between ozone and DRB1, with a RERI of 2.74 (95%CI 0.50–4.98) and 2.43 (95%CI 0.36–4.5) in the upper two tertiles, respectively. Approximately 60% of the ped-MS risk in those with HLA-DRB1*15 haplotype and high ozone exposure was attributable to the interaction between these risk factors.

Conclusions

Our data revealed additive interaction between higher exposure to ozone and DRB1 alleles on ped-MS susceptibility. Further evaluation of additional genetic variants that might play a role in ozone-induced ped-MS is underway to provide mechanistic insight.

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Author Of 2 Presentations

COVID-19 Late Breaking Abstracts

LB1231 - Demographic and Clinical Profile of Pediatric patients with Multiple Sclerosis infected with SARS-Cov2 (ID 2111)

Abstract

Background

COVID-19, the disease caused by SARS CoV2, causes severe respiratory disease, and rarely multisystem inflammatory syndrome, in some pediatric patients. Little is known about the disease course among patients with pediatric-onset multiple sclerosis.

Objectives

To describe the demographic and clinical characteristics of a subgroup of pediatric-onset multiple sclerosis (POMS) patients infected with SARS CoV2.

Methods

The Network of Pediatric Multiple Sclerosis Centers (NPMSC), a consortium of 10 US pediatric multiple sclerosis (MS) centers contributes clinical information about POMS patients and demyelinating disorders to a centralized database, the Pediatric Demyelinating Disease Database (PeMSDD), to facilitate research for this rare disorder. In addition to collecting clinical data on clinical course, comorbidities, disease modifying therapy use, and functional status, the NPMSC developed a screening questionnaire to administer to patients during standard of care visits to further evaluate their COVID- 19 status. Additionally POMS patients with confirmed or highly suspected COVID-19, will be assessed for risk factors including smoking use, recent glucocorticoid use, comorbidities; clinical presentation, including symptoms, radiological and laboratory data; COVID-19 treatments and outcomes. POMS patients will also complete the COViMS (COVID-19 Infections in MS & Related Diseases) database, a joint effort of the US National MS Society and the Consortium of MS Centers to capture information on outcomes of people with MS and other central nervous system (CNS) demyelinating diseases (Neuromyelitis Optica Spectrum Disease, or MOG antibody disease) who have developed COVID-19. Together with data collected from the PeMSDD, we will present comprehensive data on the POMS patient experience with COVID-19 and compare it to POMS patients without known or suspected COVID-19.

Results

Data collection continues. Results available by the meeting due date will describe the demographics, risk factors, treatments and outcomes of POMS with COVID-19.

Conclusions

Conclusions will be drawn pending results of data analysis. We anticipate reporting on demographic data, risk factors, outcomes and any associations with disease modifying therapy.

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Observational Studies Poster Presentation

P0848 - Characterization of Retinal Nerve Fiber Layer Thickness in a Cohort with Glutamic Acid Decarboxylase and Glycine Receptor Autoimmunity (ID 1154)

Speakers
Presentation Number
P0848
Presentation Topic
Observational Studies

Abstract

Background

Glutamic acid decarboxylase (GAD-65) and glycine receptor (GlyR) autoimmunity includes a wide range of clinical phenomena including stiff-person syndrome and epilepsy. Both GAD and GlyR interact with the retina. Optical coherence tomography (OCT) has previously been used in a variety of other neurological disorders to establish baseline characteristics and monitor disease course. This presents a noninvasive opportunity to evaluate for a biomarker that may assist with treatment of these rare but debilitating disorders.

Objectives

To provide a description of the retinal nerve fiber layer (RNFL) in patients with GAD-65 and GlyR neurological autoimmunity.

Methods

OCT measures of RNFL were studied in patients with GAD-65 and GlyR neurological autoimmunity and compared to that of 148 healthy control eyes and 472 eyes from patients with multiple sclerosis.

Results

The 15 patients were mostly female, in keeping with reported female preponderance in these conditions. We report initial post-diagnosis mean RNFL thickness and standard deviations, by sector, for the whole group, as compared with respective controls and patients with multiple sclerosis. Multiple sectors showed RNFL thinning, most apparent in the anti-GAD-65 group.

Conclusions

This study provides insight into baseline post-diagnosis RNFL thickness in a group with GAD-65 and GlyR autoimmunity, two conditions which may produce varied symptoms. While limited by sample size, RNFL thinning was most evident in the anti-GAD-65 group, and to a lesser extent, in the anti-GlyR group. This provides a baseline characterization and suggests that future studies should be done to determine the utility of OCT as a biomarker for these conditions.

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