Sumegi Janos, Seemayer Thomas A, Huang Dali, Davis Jack R, Morra Massimo, Gross Thomas G, Yin Luo, Romco Giovanni, Klein Eva, Terhorst Cox, Lanyi Arpad
Center of Human Genetics, University of Nebraska Medical Center, Omaha 68198-5454, USA.
Leuk Lymphoma. 2002 Jun;43(6):1189-201. doi: 10.1080/10428190290026240.
X-linked lymphoproliferative disease (Duncan's Disease) was first encountered by David T. Purtilo in 1969. The first communication describing the disease was published in 1975. In 1989 the disease locus was mapped to Xq25. Ten years later the gene (SH2D1A, SAP, DSHP), which is absent or mutated in XLP patients was identified. Since that the protein crystal structure of this small, SH2-domain containing protein has been solved, target molecules of the protein have been identified, physiological and pathological protein/protein interactions have been characterized, and the mouse model of the gene mutation has been developed. That said, a complete understanding of the function of the normal SH2D1A protein in immunoregulation and of the altered immune responses in XLP patients is not yet at hand. Therein lies the legacy of Purtilo's discovery for, as with other primary immunodeficiencies, these "experiments of nature" offer a window on the beauty of the immune system. In due course, the manner by which this gene orchestrates an elegant response (akin to a Mozart divertimento) to EBV infection shall be defined.
X连锁淋巴增生性疾病（邓肯氏病）于1969年首次被大卫·T·珀蒂洛发现。第一篇描述该疾病的通讯文章于1975年发表。1989年，该疾病基因座被定位到Xq25。十年后，在XLP患者中缺失或突变的基因（SH2D1A、SAP、DSHP）被鉴定出来。自那时起，这种含有SH2结构域的小蛋白的晶体结构已被解析，该蛋白的靶分子已被鉴定，生理和病理状态下的蛋白/蛋白相互作用已被表征，并且已建立该基因突变的小鼠模型。话虽如此，对于正常SH2D1A蛋白在免疫调节中的功能以及XLP患者免疫反应改变的全面理解仍未实现。这就是珀蒂洛发现的意义所在，与其他原发性免疫缺陷一样，这些“自然实验”为免疫系统的美妙之处提供了一扇窗口。随着时间的推移，该基因协调对EBV感染做出优雅反应（类似于莫扎特的嬉游曲）的方式将被明确。
