Author Of 1 Presentation
PS04.04 - Evidence for an interaction between ozone pollution and HLA-DRB1*15 alleles in pediatric multiple sclerosis
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.
We sought to examine the interaction between ozone pollution and DRB1*15 status as the main genetic variant associated with MS susceptibility.
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.
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.
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.
Author Of 1 Presentation
P1082 - Therapeutic Response in Pediatric Neuromyelitis Optics Spectrum Disorder (ID 1820)
Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune condition which can led to significant disability. Approximately 4% of the NMOSD cases are pediatric onset. At present, there are limited studies that aim at guiding physicians in their treatment choices for NMOSD in children.
To evaluate the effect of different disease modifying therapies (DMT) with respect to attack prevention in children with NMOSD.
Cohort study that included 12 clinical centers participating in the US Network of Pediatric MS Centers. Cases were validated for NMOSD diagnostic criteria and classified via serostatus as AQP4+, MOG+, or double-seronegative (DS). Clinical data, including demographics, attack details, type of initial DMT (rituximab, mycophenolate mofetil, azathioprine, IVIg) and neurological visit data were extracted from charts, centrally collected in a database, and analyzed. Treatment response in the three serostatus subgroups was evaluated. Effect of DMTs on annualized relapse rate (ARR) was assessed by negative binomial regression.
111 pediatric patients with NMOSD were identified: 80 AQP4+, 10 MOG+, 14 double seronegative (DS), and 7 with unknown serostatus (94 females and 17 males; 48 white, 47 African American, 13 other races). Mean follow-up duration was 1.9 years (SD±2.2). About 6% of patients were treatment-naive. First-line DMTs varied by serostatus: in the AQP4+ subgroup 42% used rituximab, 16% mycophenolate mofetil, 16% azathioprine, and 8% IVIg. Among MOG+ patients, 13% received rituximab, 13% azathioprine, 13% mycophenolate, and 38% IVIg. Within the DS group, rituximab was used in 21% of cases, azathioprine in 7%, mycophenolate in 21%, and IVIg in 21%. In the unknown serogroup, 33% received rituximab, 17% azathioprine, 0% mycophenolate, and 33% IVIg. The ARR calculated in all the serogroups was 0.25 (95% CI 0.13-0.46) for rituximab, 0.73 (95% CI 0.27-2.00) for azathioprine, 0.40 (95% CI 0.18-0.89) for mycophenolate, and 0.56 (95% CI 0.26-1.20) for IVIg. In the AQP4+ subgroup, the patients started on rituximab showed an ARR of 0.25 (95% CI 0.13-0.48), those on azathioprine an ARR of 0.76 (95% CI 0.24-2.39), those on mycophenolate an ARR 0.43 (95% CI 0.17-1.07), and those on IVIg an ARR of 0.63 (95% CI 0.26-1.55).
This retrospective study showed that rituximab is associated with a lowered annual relapse rate in pediatric NMOSD and in particular in the AQP4+ subgroup.