As we discuss later, the IL12B region is also associated with TAK. These data strongly suggest that ustekinumab would be a very promising therapeutic option for patients with TAK. The only established genetic component associated with TAK has been HLA-B52. The association between HLA-B*52:01 and TAK has been repeatedly shown in different populations.[33-38] There are studies reporting the importance of other alleles, including HLA-DPB1

or HLA-DRB1 alleles.[39, 40] The recent genome-wide association study (GWAS) showed an independent association in the HLA-DQB1/DRB1 locus.[41] Although HLA-B51, a strong susceptibility allele to BYL719 Behçet disease,[42] shares large parts of amino acid sequencing with HLA-B*52:01, the association between HLA-B51 and TAK was negatively reported.[34] Our recent work might provide an answer to these observed different susceptibilities.[38] Our study indicates the importance of the 67th and 171st amino acid residues for TAK susceptibility where the 67th is one of the selleck kinase inhibitor two amino acid residues not shared between HLA-B*51:01 and *52:01. Furthermore, both the amino acid positions are located at peptide binding grooves,[43-45] suggesting that peptide binding at these positions would be very important for the predisposition of the two different autoimmune diseases. A previous Mexican study suggested

the involvement of the 63rd and 67th amino acids.[46] Thus, different studies suggest the importance of the 67th amino acid of the HLA-B protein. Although HLA-B39 was reported to be associated with severe complications of TAK as well as TAK onset in a previous study,[47] the association was not observed in a recent Japanese study, and it did not find a different association between

HLA-B67:01 and TAK clinical manifestations.[48] Our recent work confirmed this lack of association Chorioepithelioma of HLA-B39 and the positive association of HLA-B*67:01.[38] HLA-B*67:01 has not been reported in Turkey and Middle-East Asia. Although GCA shows association with HLA-DR4,[49] which is not a TAK susceptibility allele, meta-analysis of TAK and GCA would reveal similarity and differences between the two large vessel arterites. Recently, we reported the first GWAS results for this disease at the same time as a US/Turkish group.[41, 50] Both groups reported IL12B as a strong susceptibility locus to TAK. Our group also reported the MLX region in chromosome 17 and a US/Turkish group reported the FCGR2A/3A region as another susceptibility locus. The US/Turkish group also reported the PSMG1 region as a suggestive locus. Our data also showed that the polymorphism in the IL12B region is associated with high incidence of AR, severity of AR and higher time-averaged CRP level as a representative of disease activity. Furthermore, our data indicated that the polymorphism of the IL12B region displayed a synergistic effect on TAK susceptibility in combination with HLA-B*52:01.