Why HLA-B27? My thirty-year quest: the Friedenwald lecture.
Why HLA-B27? My thirty-year quest: the Friedenwald lecture.
复制标题
为什么选择 HLA-B27？
DOI：
10.1167/iovs.11-8247
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发表时间：
2011
影响因子：
4.4
通讯作者：
Rosenbaum,JamesT
中科院分区：
文献类型：
--
作者：
Rosenbaum,JamesT
Jonas Friedenwald and Alan C. Woods were close friends. Friedenwald was chief of pathology at the Wilmer Eye Institute at Johns Hopkins Medical School. AC Woods was the director of the Wilmer for more than two decades, and he and Supreme Court Justice Felix Frankfurter delivered eulogies when Dr. Friedenwald passed away in 1955. Both Woods and Friedenwald are extremely important in shaping the remarks in this essay. Friedenwald’s contribution is honored in the naming of the lectureship, and Woods’ provocative observations on the pathogenesis of uveitis foreshadowed my own career. AC Woods injected rabbits intravenously with the filtrate from cultured bacterial broth and frequently observed a uveitis in these animals. In 1916 Woods wrote,“Poisons can be isolated from non-pathogenic ferment producing bacteria which have a definite action on the uveal tract in the eye.” 1 In addition, he commented,“Histologically the eyes showed a round cell infiltration about the ciliary processes…”. 1 The observations from Woods and others were extremely influential in the effort to understand uveitis. For several decades, it was accepted that uveitis often results from occult bacterial infection. In a publication from the Mayo Clinic in 1932, Rosenow and Nickel2 wrote,“In many cases streptococci having elective localizing power have been isolated in uveitis.”“Different foci have been found. The most frequent were teeth, tonsils, prostate, or cervix. Removal of these foci….” In other words, hysterectomy or prostatectomy were potential forms of treatment for uveitis in the 1930s. The work of Rosenow and Nickel was presented at the second annual meeting of the Association for Research in Ophthalmology, an organization subsequently known as ARVO. As implied in the title of this lecture, I want to discuss the potential mechanism by which the human leukocyte antigen HLA-B27 predisposes to uveitis. As background, I will outline briefly the HLA system, provide an overview of the clinical problem of uveitis, discuss selected observations which my laboratory has made in animal models, and then return to the statement by AC Woods to ask whether his concept of occult infection could have been correct. If I succeed, I hope to persuade my reader that HLA-B27 and bacterial flora are closely related topics.My scientific mentor was Hugh O. McDevitt, a professor at Stanford and a member of the National Academy of Sciences. By injecting short repetitive peptide sequences into mice and rabbits, McDevitt and Sela3 astutely observed that some animals made an immune response while other animals were incapable of an immune response. He further determined that the major histocompatibility complex was responsible for the ability to mount that immune response. 4 For this observation, McDevitt is appropriately credited as the discoverer of immune response genes. In a seminal essay in the journal Science nearly 40 years ago, Baruj Benacerraf and McDevitt5 wrote,“This type of genetic control of specific immune response may play an important role in susceptibility to a variety of diseases in both animals and man.” Within a few months, McDevitt’s hypothesis was validated by the demonstration that HLA-B27, then known as HLA 27, profoundly influenced susceptibility to ankylosing spondylitis, 6, 7 reactive arthritis, 3 and acute anterior uveitis. 8 A great deal is now known about the human leukocyte antigen or HLA system, which constitutes the major histocompatibility complex in man. Several major loci code for HLA alleles which are highly polymorphic. The B locus alone has greater than 700 distinct alleles. In fact HLA-B27 is not a single allele; 65 distinct subsets of …
