title: HLA, PTPN22 and PD-1 associations as markers of autoimmunity in neuromyelitis optica.
abstract: BACKGROUND
  Neuromyelitis optica (NMO) is a disease with autoimmune characteristics. A genetic autoimmune dependency for NMO has not been clarified in detail.
  
  
  OBJECTIVE
  To investigate immunogenetic aspects of NMO.
  
  
  METHODS
  Forty-one patients with NMO and 42 patients with multiple sclerosis (MS) were diagnosed in a population-based Caucasian cohort. HLA DQA1, DQB1, and DRB1 alleles were determined. Polymorphisms in programmed death 1 (PD-1) PD-1.3 G/A and protein tyrosine phosphatase non-receptor 22 (PTPN22) 1858 C/T were genotyped.
  
  
  RESULTS
  In the NMO group 15% had other autoimmune disorders and 39% had family occurrence of autoimmunity, comparable to MS. A higher frequency of a family history (17%) of NMO and MS was found in the NMO group (p < 0.026). The frequency of HLA-DQB1*0402 allele was increased in NMO (p after Bonferroni correction, cp < 0.035) and the HLA-DRB1*15 and DQB1*06 alleles were increased in MS (cp < 0.0027, cp < 0.01), compared to controls. No associations of the PTPN22 1858 T were detected. The PD-1.3A allele was increased both in NMO (p < 0.0023) and in MS patients (p < 0.028) compared to controls.
  
  
  CONCLUSIONS
  Patients with NMO had frequent co-existence of autoimmunity and family occurrence of NMO and MS. The PD-1.3A allele was associated with NMO. The data suggest genetic autoimmune dependency of NMO.
authors: The Multiple Sclerosis Clinic of Southern Jutland, Sonderborg, Denmark. nasgari@health.sdu.dk
authors: N
authors: N
authors: Asgari
authors: C
authors: C
authors: Nielsen
authors: E
authors: E
authors: Stenager
authors: K O
authors: KO
authors: Kyvik
authors: S T
authors: ST
authors: Lillevang
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics* / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D005260:Female; D005455:Fluorescent Antibody Technique; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000235:genetics; D009471:Neuromyelitis Optica / Q000150:complications / Q000235:genetics / Q000276:immunology*; D011110:Polymorphism, Genetic; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics*; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D011863:Radioimmunoassay; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22