Abstract: Viral and Genetic Risk Factors For Pediatric Neuromyelitis Optica (The 27th Annual Meeting of the CMSC and the 5th Cooperative Meeting of the CMSC-ACTRIMS)

Saturday, June 1, 2013

Sirisha Grandhe, BA , Neurology, University of California, San Francisco, Bakersfield, CA

Jennifer Graves, MD, PhD , Neurology, University of California, San Francisco, San Francisco, CA

Ellen M Mowry, MD , Neurology, University of California, San Francisco, San Francisco, CA

Lauren Krupp, MD , Neurology, Stony Brook University Medical Center, East Setauket, NY

Tanuja Chitnis, MD , Neurology, Massachusetts General Hospital, Boston, MA

Eluen A Yeh, MD , Division of Neurology, Hospital for Sick Children, Toronto, ON, Canada

Nancy Kuntz, MD , Neurology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL

Jayne Ness, MD , Neurology, Children's Hospital Alabama, Birmingham, AL

Anita L Belman, MD , Neurology, Stony Brook University Medical Center, East Setauket, NY

Maria Milazzo, NP , Neurology, Stony Brook University Medical Center, Stony Brook, NY

Mark Gorman, MD , Neurology, Boston Children's Hospital, Boston, MA

Bianca Weinstock-Guttman, MD , Neurology, University of Buffalo, Buffalo, NY

Moses Rodriguez, MD , Neurology, Mayo Clinic, Rochester, MN

Marc Patterson, MD , Neurology, Mayo Clinic, Rochester, MN

Judith A James, MD , Rheumatology, Oklahoma Medical Research Foundation, University of Oklahoma, Oklahoma City, OK

Emmanuelle Waubant, MD, PhD , Neurology, University of California, San Francisco, San Francisco, CA

Background:

It is unclear whether the genetic and environmental risk factors of pediatric multiple sclerosis (MS) and neuromyelitis optica (NMO) overlap.

Objectives:

We sought to determine whether genetic and environmental risk factors reported for MS, such as HLA-DRB1*15:01 status, past infections with Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus 1 (HSV-1), and level of 25(OH) vitamin D, increase the susceptibility to develop pediatric NMO.

Methods:

Sera were collected from patients who were diagnosed with NMO by the Pediatric MS Network or donated samples to the Accelerated Cure/Guthy Jackson Biobank. Pediatric MS and neurological control samples were also provided by the Network. Antibodies against EBV (EBNA1 and VCA), HSV-1, and CMV were measured by ELISA. Serum 25(OH)-vitamin D was measured by chemoluminescent immunoassay. HLA-DRB1 status was measured via PCR. The association of herpes virus exposure, HLA-DRB1 status, and vitamin D level with diagnosis was evaluated by logistic regression adjusting for age, gender, race, and ethnicity.

Results:

Serum and DNA were available from 34 pediatric NMO, 186 pediatric MS/CIS, and 33 pediatric neurological controls. Median age at NMO onset was 11.0 years. Median disease duration at sample collection was 3.61 years. Compared to patients with MS, those with pediatric NMO had a lower frequency of positive DRB1 status (OR 0.180, 95%CI: .035 to 0.927, p=0.040) and HSV-1 exposure (OR 0.147, 95%CI: 0.025 to 0.862, p=0.034). NMO patients were more likely exposed to CMV but less likely to EBV, but neither of these findings reached statistical significance. Analyses of 25(OH) vitamin D association are ongoing.

Conclusions:

NMO patients have lower prevalence of HLA-DRB1*15:01 and HSV-1 exposure compared to those with MS but these prevalences are similar to controls. Larger case-control studies are needed to confirm these findings.

Acknowledgements: The Guthy Jackson Charitable Foundation

P7 Viral and Genetic Risk Factors For Pediatric Neuromyelitis Optica