Background/Purpose: An association between Behçet’s Syndrome (BS) and HLA-B*51 is widely reported among many different ethnic groups. Recently, a few reports from Taiwan, Greece and Japan were published that indicated HLA-A*26 is also associated with BS independently from HLA-B*51, but these studies may have some limitations. These limitations include small numbers, were not written in English, only analyzed BS with ocular lesions, or were mainly led by ophthalmologists. Therefore, the association between HLA-A*26 and BS still remains unclear. For this report we studied phenotype frequencies (PF) of HLA-A and HLA-B in Japanese BS patients seen by not only ophthalmologists but also experts in different specialties, mainly rheumatologists. 

Methods :  All BS patients seen at tertiary care centers of Kameda Medical Center and St. Luke’s International Hospital in Japan between 2003-2012 were included in the analysis. Patients were mainly seen by rheumatologists, followed by neurologists, dermatologists, ophthalmologists, and gastroenterologists. The diagnosis of BS was made on clinical manifestation and expert opinions. Charts were reviewed for DNA typing of HLA alleles and disease manifestations. To compare PF, we adopted data from the central bone marrow data center registry of Japanese Red Cross Society (n=263016) as a control for the general population in Japan. The significance of the distribution of phenotypes was analyzed by one-sample proportions test and the primary P-values were corrected by using the Bonferroni correction (Pc). We analyzed manifestations by Fisher’s exact probability test or t-test. 

Results : As for HLA-A and HLA-B, 80 and 81 patients were tested respectively (88 patients were eligible for HLA-B*51 analysis) and 6 HLA-A and 19 HLA-B alleles were detected. Of all, PF of HLA-A*26 was significantly higher than the general Japanese population (42.5% vs. 22.6%, Pc=8.0 x10^-4). The same is true for HLA-B*51 (44.3% vs. 17.1%, Pc=7.1×10^-10). No significant differences were seen in other HLA alleles. Secondly, we analyzed the difference in manifestations of BS patients stratified by HLA-A*26 or HLA-B*51. No significant difference was seen except for age of onset, which was younger in patients with HLA-B*51 than without it (mean±SD (years): 34.1±13.6 vs. 41.3±17.9, P=0.041). There is also a tendency that gastrointestinal (GI) lesions are less likely for patients with HLA-B*51 (28.2% vs. 46.9%, P=0.082). We detected no significant difference of manifestations between HLA-A*26 positive patients and negative patients.

Conclusion: HLA-A*26 is found to be alleles for BS susceptibility among BS patients not only with ocular lesions but also various manifestations in Japan. Moreover, our study also showed that patients with HLA-B*51 have younger onset and a lower tendency of GI lesions.

Table 1: Phenotype frequency of HLA-A and HLA-B in BS patients compared with the general population in Japan (extracted data were shown)

	PF of BS patients (%)	PF of the general Japanese (%)	P-value	Pc-value
HLA-A*02	46.3	42.9	0.62
-A*24	58.8	60.1	0.83
-A*26	42.5	22.6	3.6 x10-5	8.0 x10-4
-A*33	58.8	60.1	0.06
HLA-B*51	44.3	17.1	3.2×10-11	7.1x10-10
-B*52	16.1	21.0	0.34
-B*54	16.1	14.6	0.83

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-strong-association-between-hla-a26-and-behcets-syndrome-in-japanese-patients-from-two-center-cohort-study-of-behcets-syndrome/