Anti-BTNL2 polyclonal antibody [Alexa Fluor® 350]

The major histocompatibility complex human leukocyte antigen (HLA)-DRB1*15 (DR2) haplotype is strongly associated with risk of multiple sclerosis (MS). The primary susceptibility has been localized to only similar to 200 kb encompassing the HLA-DR and -DQ loci. Further dissection of disease association with this region is demanding because of the high levels of linkage disequilibrium (LD). Recently, evidence was obtained for the involvement of a gene, potentially encoding an immune co-receptor, in another DR2-associated inflammatory condition, sarcoidosis. The implicated gene, BTNL2, is adjacent to DR and is in strong LD with HLA-DRB1. This fact, combined with a sequence relationship between BTNL2 and myelin oligodendrocyte glycoprotein, an autoantigen associated with MS, makes the gene an attractive candidate. To determine whether BTNL2 contributes to MS, we genotyped 1136 well-characterized MS families from the UK and the USA, as well as an African-American case-control data set, making this among the largest genetic studies in MS. Family-based and case-control association studies were performed for the BTNL2 and HLA-DRB1 loci. In all family data sets, the protein-truncating allele of BTNL2, implicated in sarcoidosis, was significantly over-transmitted to cases (combined data sets: global P=2.4x10(-11)). Given that the protein-truncating allele of BTNL2 virtually always occurred with DRB1*15, an effect could only be tested in DRB1*15-negative individuals or pedigrees. However, despite adequate power to detect an independent association, no difference in transmission of BTNL2 alleles or genotypes was observed in DRB1*15-negative individuals with MS. Conditional logistic regression modeling also strongly supported the conclusion that BTNL2 does not confer additional disease risk. The association of BTNL2 with MS observed in the African-American data set was also secondary to the primary DRB1*15 association.

The aim of this study was to test the microsatellites in the Type 1 Diabetes Genetics Consortium major histocompatibility complex (MHC) data set for association with type 1 diabetes (T1D) independent of the HLA-DRB1, -DQA1 and -DQB1 genes. The data set was edited to contain only one affected child per family, and broad ethnic subgroups were defined. Genotypes for HLA-DRB1, -DQA1 and -DQB1 were replaced by a haplotype code spanning all three loci, with phase inferred based on common haplotypes. The final data set contained 8190 samples in 2301 families, 59 microsatellites and the DRB1-DQA1-DQB1 haplotype code. Statistical analyses consisted of conditional logistic regression and haplotype estimations and linkage disequilibrium calculations. The data set was screened using a main effects test approach adjusted for DRB1-DQA1-DQB1, and significant results tested for validity. After these procedures, four markers remained significant at the Bonferroni-corrected threshold: D6S2773 (p = 0.00014), DG6S185 (p = 0.00015), DG6S398 (p = 0.00043) and D6S2998 (p = 0.00015). These results were supported by allelic tests conditioned on DRB1-DQA1-DQB1 haplotypes, except for DG6S185, which may contain artefacts. We have identified three microsatellites that mark additional risk factors for T1D at highly significant levels in the MHC. Further analyses are needed to establish the relationship with other possible genetic determinants in this region.