Abstract
Purpose :
Behcet's disease is an intractable inflammatory disease of unknown cause with recurrent acute inflammation in various organs. The major symptoms are oral aphthous ulcers, skin lesions, ocular lesions, and genital ulcers, often accompanied by minor symptoms such as arthritis, epididymitis, gastrointestinal involvements, vascular lesions, and central nervous system lesions. Bechet's disease is a multifactorial genetic disorder known to associate strongly with the HLA-B*51 allele of the HLA-B gene across races. In addition, recent genetic studies have reported several new genetic factors for Behcet's disease. On the other hand, the factors governing the formation of various symptoms of Behcet's disease have not yet been determined, and the whole pathology of Behcet's disease has not yet been elucidated. In this study, we evaluate the influence of genetic factors on the formation of clinical symptoms of Behcet's disease.
Methods :
Regarding the eighteen reported susceptibility genes for Behcet's disease that have been reported so far (HLA-B*51, HLA-A*26, IL10, IL23R-IL12RB2, CCR1, STAT4, KLRC4, ERAP1, TNFAIP3, MEFV, FUT2, IL12A, IL1A-IL1B, RIPK2, ADO-EGR2, LACC1, IRF8, CEBPB-PTPN1), 608 patients in Japan were stratified according to the presence or absence of risk alleles of each gene to evaluate the association with the formation of clinical symptoms of the disease.
Results :
According to the stratified analysis, we identified susceptibility of HLA-A*26 for ocular symptoms, genital ulcers, and central nerve lesions, IL23R-IL12RB2 for arthritis, IL10 for oral aphthous ulcers, skin symptoms, ocular symptoms, and central nerve lesions, STAT4 for genital ulcers, CCR1 for vascular lesions, KLRC4 for epididymitis, and IRF8 for ocular symptoms and epididymitis. Associations were observed between the combination of HLA-A*26, and IL10 conferred the risk for central nervous system lesions. The combination of HLA-A*26, IL10, and IRF8 was a risk for ocular involvement. The combination of HLA-A*26 and STAT4 was a risk for genital ulcers. The combination of KLRC4 and IRF8 significantly increased the incidence of epididymitis.
Conclusions :
This study has comprehensively found genetic factors that influence the formation of clinical symptoms of Behcet's disease. In the future, it may be possible to predict clinical symptoms by genetic factors of an individual patient.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.