Anti-TNFSF4 monoclonal antibody, clone SN245M Functional Grade

Purpose Vogt-Koyanagi-Harada (VKH) disease is a rare autoimmune disease. The autoimmune response in VKH disease is against the melanin-producing cells; therefore, in affected individuals melanocyte-containing organs manifest disease symptoms including eyes, ears, skin and nervous system. VKH is a multifactorial disease, and the precise cause of the VKH disease is unknown. Studies have suggested that both environmental and genetic factors are responsible for the VKH disease. In this review, the authors have collected all the available literature on the genetics of VKH to their knowledge and discussed the role of genetic variants in causing VKH disease. Methods An extensive literature search was performed in order to review all the published studies regarding VKH clinical phenotyping and genetic variants in VKH disease. Medline, PubMed, Cochrane library, and Scopus was searched using combination of keywords. Results It was found that variants in HLA genes,IL-12b,TNFSF4, andmiR-20-5pgenes are significantly associated with VKH; however, variants in genesATG10,TNIP1andCLEC16Adid not achieve significant genome-wide association threshold. Moreover, polymorphisms inTNIP1andCLEC16Aplay a protective role against VKH. Conclusion The authors conclude that increased sample size and a more homogeneous VKH patient population may reveal a significant association of variants inATG10, TNIP1 and CLEC16Agenes with VKH disease.

Background Evidence is beginning to emerge that there may be susceptibility loci for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) that are common to both diseases. Objective To investigate single nucleotide polymorphisms that have been reported to be associated with SLE in a UK cohort of patients with RA and controls. Methods 3962 patients with RA and 9275 controls were included in the study. Eleven SNPs mapping to confirmed SLE loci were investigated. These mapped to the TNFSF4, BANK1, TNIP1, PTTG1, UHRF1BP1, ATG5, JAZF1, BLK, KIAA1542, ITGAM and UBE2L3 loci. Genotype frequencies were compared between patients with RA and controls using the trend test. Results The SNPs mapping to the BLK and UBE2L3 loci showed significant evidence for association with RA. Two other SNPs, mapping to ATG5 and KIAA1542, showed nominal evidence for association with RA (p=0.02 and p=0.02, respectively) but these were not significant after applying a Bonferroni correction. Additionally, a significant global enrichment in carriage of SLE alleles in patients with RA compared with controls (p=9.1x10(-7)) was found. Meta-analysis of this and previous studies confirmed the association of the BLK and UBE2L3 gene with RA at genome-wide significance levels (p<5x10(-8)). Together, the authors estimate that the SLE and RA overlapping loci, excluding HLA-DRB1 alleles, identified so far explain similar to 5.8% of the genetic susceptibility to RA as a whole. Conclusion The findings confirm the association of the BLK and UBE2L3 loci with RA, thus adding to the list of loci showing overlap between RA and SLE.