title: Immune response profiling identifies autoantibodies specific to Moyamoya patients.
abstract: BACKGROUND
  Moyamoya Disease is a rare, devastating cerebrovascular disorder characterized by stenosis/occlusion of supraclinoid internal carotid arteries and development of fragile collateral vessels. Moyamoya Disease is typically diagnosed by angiography after clinical presentation of cerebral hemorrhage or ischemia. Despite unclear etiology, previous reports suggest there may be an immunological component.
  
  
  METHODS
  To explore the role of autoimmunity in moyamoya disease, we used high-density protein arrays to profile IgG autoantibodies from the sera of angiographically-diagnosed Moyamoya Disease patients and compared these to healthy controls. Protein array data analysis followed by bioinformatics analysis yielded a number of auto-antibodies which were further validated by ELISA for an independent group of MMD patients (n = 59) and control patients with other cerebrovascular diseases including carotid occlusion, carotid stenosis and arteriovenous malformation.
  
  
  RESULTS
  We identified 165 significantly (p < 0.05) elevated autoantibodies in Moyamoya Disease, including those against CAMK2A, CD79A and EFNA3. Pathway analysis associated these autoantibodies with post-translational modification, neurological disease, inflammatory response, and DNA damage repair and maintenance. Using the novel functional interpolating single-nucleotide polymorphisms bioinformatics approach, we identified 6 Moyamoya Disease-associated autoantibodies against APP, GPS1, STRA13, CTNNB1, ROR1 and EDIL3. The expression of these 6 autoantibodies was validated by custom-designed reverse ELISAs for an independent group of Moyamoya Disease patients compared to patients with other cerebrovascular diseases.
  
  
  CONCLUSIONS
  We report the first high-throughput analysis of autoantibodies in Moyamoya Disease, the results of which may provide valuable insight into the immune-related pathology of Moyamoya Disease and may potentially advance diagnostic clinical tools.
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA.
authors.forename: Tara K
authors.initials: TK
authors.lastname: Sigdel
authors.forename: Lorelei D
authors.initials: LD
authors.lastname: Shoemaker
authors.forename: Rong
authors.initials: R
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Atul J
authors.initials: AJ
authors.lastname: Butte
authors.forename: Minnie M
authors.initials: MM
authors.lastname: Sarwal
authors.forename: Gary K
authors.initials: GK
authors.lastname: Steinberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood*; D002533:Cerebral Angiography; D002561:Cerebrovascular Disorders / Q000000981:diagnostic imaging / Q000276:immunology / Q000503:physiopathology; D019295:Computational Biology / Q000379:methods; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D009072:Moyamoya Disease / Q000000981:diagnostic imaging / Q000276:immunology* / Q000503:physiopathology; D040081:Protein Array Analysis / Q000379:methods; D011499:Protein Processing, Post-Translational; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G