Dog leukocyte antigen class II alleles and haplotypes associated with meningoencephalomyelitis of unknown origin in Chihuahuas

Idiopathic non-infectious meningoencephalomyelitis (NIME), which is thought to be an immune-mediated disease, is a common inflammatory disease in dogs. Meningoencephalomyelitis of unknown origin (MUO), a subgroup of NIME, consists of necrotizing meningoencephalitis (NME), necrotizing leukoencephalitis, and granulomatous meningoencephalomyelitis. Recent studies have shown associations between disease development and dog leukocyte antigen (DLA) class II genes in NME in Pugs and in NIME in Greyhounds. This study focused on Chihuahuas, which have a high incidence of MUO and are one of the most common dog breeds in Japan. Because the development of MUO seems to be associated with DLA class II genes, we aimed to evaluate the association between DLA class II genes and MUO development in Chihuahuas. Blood samples were obtained from 22 Chihuahuas with MUO (MUO group) and 46 without neurological diseases (control). The allele sequences of three DLA class II loci were determined, and haplotypes were estimated from these data. In total, 23 haplotypes were detected. The frequency of one haplotype (DLA-DRB1*015:01--DQA1*006:01--DQB1*023:01) was significantly higher in the MUO group than in the control group (odds ratio, 7.11; 95% confidence interval, 1.37-36.81; P=0.0141). The results suggest that the development of MUO in Chihuahuas may be associated with DLA class II genes. Because the identified risk haplotypes differed from those of other breeds, the pathogenesis of NIME-related diseases may differ among dog breeds.