HLA, PTPN22 and PD-1 associations as markers of autoimmunity in neuromyelitis optica

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. Conclusion: 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.