Along with human leukocyte antigen gene encoding B*51 (HLA-B*51) and areas including the major histocompatibility complex class I, genome-wide association studies have recognized numerous other BD susceptibility genes including those encoding interleukin (IL)-10, IL-12 receptor β 2 (IL-12RB2), IL-23 receptor (IL-23R), C-C chemokine receptor 1 gene, signal transducer and activator of transcription 4 (STAT4), endoplasmic reticulum aminopeptidase (ERAP1), and genes encoding killer cell lectin-like receptor family members (KLRC4-KLRK1).
Furthermore, a positive correlation was observed between IL-10 serum levels and ocular manifestations in BD patients, in contrast to those of IL-17, showing no correlation with the different clinical manifestations.
The distinct effects of both enzymes on the HLA-B*51 peptidome provide a basis for their differential association with Behçet's disease and suggest a pathogenetic role of the B*51:01 peptidome.
Genetic variants of ERAP1 (leading to distinct allotypes) are linked with specific autoinflammatory disorders, such as ankylosing spondylitis and Behçet's disease.
Treg and Th17 cell frequencies and Th17 RORγt expression were significantly elevated, and IL-10 concentration in Treg cell supernatants was significantly lower in BD patients than in controls.
Along with human leukocyte antigen gene encoding B*51 (HLA-B*51) and areas including the major histocompatibility complex class I, genome-wide association studies have recognized numerous other BD susceptibility genes including those encoding interleukin (IL)-10, IL-12 receptor β 2 (IL-12RB2), IL-23 receptor (IL-23R), C-C chemokine receptor 1 gene, signal transducer and activator of transcription 4 (STAT4), endoplasmic reticulum aminopeptidase (ERAP1), and genes encoding killer cell lectin-like receptor family members (KLRC4-KLRK1).
Altered trimming of microbial and/or endogenous peptides by endoplasmic reticulum aminopeptidase 1 (ERAP1), presented by <i>HLA-B</i><sup>*</sup><i>51</i>, may play a key role in BD pathogenesis causing an alteration in T cell balance with downregulation of Tregs and expansion of Th1 and Th17.
To our knowledge, this is the first analysis of KIR3DL1/S1 allelic variation in Behçet disease and may provide insight into the pathogenic role of <i>HLA-B*51</i> and its interaction with KIR3DL1/S1.
This study was conducted on the two most consistently BS-associated ERAP1 polymorphisms, rs17482078 (NG_027839.1:g.35983G>A) and rs27044 (NG_027839.1:g.35997C>G) to analyse their distribution in 55 Italian BS patients and 65 ethnically matched controls (healthy controls, HC) and to test their association with BS risk.
In conclusion, two peptides that had high affinity to HLA-B*51:01 in computerized binding prediction showed significantly higher response in HLA-B*51:01-positive patients with BD, indicating the usefulness of computerized simulations for identifying autoreactive peptides to HLAs.
Our findings suggest that gene-gene interactions between HLA-B*51 and ERAP1 variants is important for BD development, however, ERAP1 variants which interact with HLA-B*51 may differ among disease phenotypes or populations.
Therefore, the goal of this study was to measure the correlation of the IL-10 gene polymorphisms with the susceptibility to Behçet's disease compared with the control group in the Azeri population and to determine the expression of this gene in the two groups.
Among these variants, the genetic variant associated with Behçet's disease in the <i>HLA-B</i>/<i>MICA</i> region, which tags <i>HLA-B*51</i>, is within novel long intergenic noncoding RNA transcripts that are exclusively expressed from the haplotype with the protective but not the disease risk allele.
The objective of the present study was to clarify the pathological roles of CCR1 and IL10 loci identified by previous BD genome-wide association studies (GWASs).