Debinski H S, Lee C S, Dhillon A P, Mackenzie P, Rhode J, Desmond P V
Department of Gastroenterology, St Vincent's Hospital, Melbourne, Vic.
Pathology. 1996 Aug;28(3):238-41. doi: 10.1080/00313029600169064.
The diagnosis of Gilbert's syndrome, a condition characterised by mild jaundice related to chronic unconjugated hyperbilirubinemia, is often presumptive and the pathogenesis is incompletely understood. It would be of interest to develop an immunohistochemical staining method to confirm a diagnosis of Gilbert's syndrome. To this end liver tissues from ten patients with a presumed diagnosis of Gilbert's syndrome and six normal controls were examined by immunohistochemistry with polyclonal antibodies raised to UDP-glucuronosyltransferase (UGT). All subjects had normal liver biopsies by hemotoxylin and eosin staining. In normal human liver specific staining for UGT was seen diffusely in all hepatocytes of the hepatic lobule with zone 3 accentuation. There was a reduction of immunostaining throughout the hepatic lobule in all specimens from patients with Gilbert's syndrome and faint residual staining was seen in zone 3. This thus proved a useful method to confirm a clinical diagnosis of Gilbert's syndrome. Raising monospecific antibodies to UGT may give an insight into polypmorphisms of phase II drug metabolism. Bosma et al.* have recently provided evidence from in vitro studies that subjects with Gilbert's syndrome have a putative defect in the promoter region of the gene encoding UDP-glucuronosyltransferase 1, resulting in reduced transcription. These studies have yet to be confirmed from human biopsy specimens and the possibility of second mutations in intronic sequences affecting the stability of UDP-glucuronosyltransferase 1 m RNA are being explored. *Bosma PJ, Chowdhury JR, Bakker C et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome. N Engl J Med 1995; 333: 1171-5.
吉尔伯特综合征的特征是与慢性非结合性高胆红素血症相关的轻度黄疸，其诊断通常是推测性的，发病机制尚未完全明确。开发一种免疫组织化学染色方法来确诊吉尔伯特综合征将是很有意义的。为此，我们用针对尿苷二磷酸葡萄糖醛酸基转移酶（UGT）的多克隆抗体，通过免疫组织化学方法检查了10例疑似吉尔伯特综合征患者和6例正常对照的肝组织。所有受试者的肝活检苏木精-伊红染色均正常。在正常人类肝脏中，UGT的特异性染色在肝小叶的所有肝细胞中弥漫可见，以3区更为明显。吉尔伯特综合征患者的所有标本在整个肝小叶的免疫染色均减少，仅在3区可见微弱的残留染色。因此，这证明了这是一种确诊吉尔伯特综合征临床诊断的有用方法。制备针对UGT的单特异性抗体可能有助于深入了解II期药物代谢的多态性。博斯马等人*最近通过体外研究提供了证据，表明吉尔伯特综合征患者在编码尿苷二磷酸葡萄糖醛酸基转移酶1的基因启动子区域存在推定缺陷，导致转录减少。这些研究尚未从人类活检标本中得到证实，并且正在探索内含子序列中的二次突变影响尿苷二磷酸葡萄糖醛酸基转移酶1 mRNA稳定性的可能性。*博斯马PJ、乔杜里JR、巴克尔C等人。吉尔伯特综合征中胆红素尿苷二磷酸葡萄糖醛酸基转移酶1表达降低的遗传基础。《新英格兰医学杂志》1995年；333:1171 - 1175。
