Behçet’s disease, the Silk Road and HLA‐B51: historical and geographical perspectives

Abstract

Behçet's disease (BD), also known as the Silk Road disease, is a blinding inflammatory disorder of young adults found predominantly between the Mediterranean basin and the Orient, and is strongly associated with the major histocompatibility complex (MHC) antigen HLA-B51. In this article we review the history of Behçet's disease since its first description by Hippocrates, the development of the trading routes collectively known as the Silk Road and the effect of population movement on the distribution of HLA-B51. The global distribution of this antigen among healthy control populations bears a striking similarity both to the ancient trading routes and the distribution of Behçet's disease, suggesting a genetic risk that migrated in parallel with population movement between the Mediterranean and Asia. However, certain indigenous Amerindian peoples have a high prevalence of HLA-B51 but no reported cases of BD. Furthermore, a clear genealogical relationship exists between eastern, but not central, Siberian populations with the Amerindians. Since a high level of recombination within the MHC is known to have occurred in these eastern populations before their migration into Beringia, we suggest that disruption of genetic loci in linkage disequilibria with HLA-B51 may be one reason for the absence of disease in these high HLA-B51-bearing populations. However, a contributory influence of environmental factors is not excluded by this data, and the wide variation that exists in relative risk of HLA-B51 even within Europe would support other non-genetic risk factors on the Silk Road which may be absent, or non-contributory to disease, in the Americas.

Survey and Validation of the Criteria for Behcet's Disease Recently Used in Korea: a Suggestion for Modification of the International Study Group Criteria

“…As for the expected weight of evidence, genital ulcerations revealed the greatest value, and skin lesions, PR, ROUs, HLA-B51, ocular lesions, and ileocecal ulcerations in order showed the relatively good performance. However, other features, such as CNS lesions, vascular lesions, peripheral arthritis, and epididymitis, disclosed negligible val- (17). HLA-B51 was separately set as a finding to help for classification or diagnosis.…”

Ocular involvement is associated with HLA-B51 in Adamantiades–Behçet's disease

“…19 Among different genetic markers, the class I HLA-B5 and -B51 gene on chromosome 6p21 is in association with ABD. 20,21 The relative risk of ABD in HLA-B51-positive patients is 13.3 for Turkey, 6.7 for Japan, and 1.3 for the United States of America. 22 HLA-B51 and its suballeles, B5101 and 5121, are important for antigen synthesis of CD8 þ cytotoxic suppressor T cells.…”

Familial Behçet's Disease of Adult Age: A Report of 4 Cases from a Behçet Family

“…In a study its prevalence was shown to be as low as 0.4% in Turkey (14). HLA B51, a well-connected allele with BD was also positive in three of our patients and while its prevalence in Turkish BD population is 77%; in healthy Turkish subjects its prevalence was reported to be 26% (15). Thus, as being a rare allele in the Turkish population with a known association with BD, positivity of Cw16 in three patients from the same family was found to be important and it should be investigated further to exclude accidental coincidence.…”