Objective:

Determine whether antibodies to AQP4 are present in pre-symptomatic serum from patients with neuromyelitis spectrum disorder (NMOSD) in the DoDSR

Background:

NMOSD is an autoimmune disease primarily targeting the spinal cord and optic nerve, leading to paralysis and blindness. Antibodies directed against AQP4 are a key element of disease pathogenesis and provide a disease-specific marker of NMOSD pathology. One small study of patients with myasthenia gravis suggested that antibodies to AQP4 may be present as long as 16 years prior to onset of NMOSD; however, difficulty obtaining pre-symptomatic serum samples for rare diseases has limited our ability to test for the presymptomatic presence of this biomarker.

Design/Methods:

Subjects were identified through the DoD/Defense Medical Surveillance System (DMSS) utilizing ICD codes for Neuromyelitis Optica (ICD-9: 341.0, ICD10: G36.0). After verifying the clinical and laboratory records of each patient to ensure the correct diagnosis, a list of these potential subjects was sent to the Armed Forces Health Surveillance Division (AFHSD) to determine which had serum specimens. Serum from these patients, as well as age and sex-matched healthy and disease (multiple sclerosis) controls, was acquired from the DoDSR at the time closest to diagnosis and at timepoints up to 20 years prior to diagnosis.  Serum from these samples was analyzed for AQP4 antibodies using Euroimmun fixed cell-based assays performed at ARUP. 

Results:

64 people who met inclusion criteria were identified and analyzed for autoantibodies to AQP4. Of 32 AQP4-positive patients analyzed for seropositivity in the sample prior to disease onset, 20 (62.5%) were positive for AQP4 (mean -940 days, SD -400.5); analysis of older serum samples will be presented at the conference. 

Conclusions:

Antibodies to AQP4 are present in a subset of patients with NMOSD years prior to diagnosis. Additional studies are needed to determine what factors predict onset of disease.