Hepatology：原发性胆汁型肝硬化早期诊断的方法

生物谷

    生物谷报道：Mayo  Clinic的科学家最近发现，患有原发性胆汁型肝硬化（PBC）的患者的第一级亲属（父母、兄弟姐妹、子女）更有可能在血液中存在该疾病的生物标记物。利用这一信息，医生就可以对PBC患者亲属进行简单的血液测试，以便在造成不可逆转的肝脏损伤之前进行诊断和治疗。结果发表在本月的Hepatology上。

    抗线粒体抗体是PBC的生物标记分子。研究分析了306位PBC患者的一级亲属以及196位健康成人的亲属的抗线粒体抗体。在前者血液内存在率为13.1%，后者为1％。而在女性中这一数字更高，姐妹是20.7%，母亲15.1％，女儿9.8%。虽然出现这些抗体并不意味着患有PBC，但这表明对疾病存在易感性，特别是结合考虑家族病史情况下。

    主要作者，Mayo  Clinic的Konstantinos  Lazaridis说：“大部分PBC病人没有症状，但早期诊断很重要，因为这能延缓疾病进程，防止肝衰竭。

    Lazadidis还认为以上发现对于更好了解PBC的基因易感性也很重要。小组计划继续对PBC病人的一级亲属进行长期跟踪分析，来进一步确认以上发现，并揭开导致疾病的原因。（教育部科技发展中心）

    英文原文链接：http://www.physorg.com/news108655560.html

原始出处:

Hepatology

Volume 46, Issue 3 , Pages 785 - 792

Published Online: 6 Aug 2007

Autoimmune, Cholestatic, and Biliary Disease

Increased prevalence of antimitochondrial antibodies in first-degree relatives of patients with primary biliary cirrhosis

Konstantinos N. Lazaridis 1 *, Brian D. Juran 1, Gwen M. Boe 1, Joshua P. Slusser 2, Mariza de Andrade 2, Henry A. Homburger 3, Karthik Ghosh 4, E. Rolland Dickson 1, Keith D. Lindor 1, Gloria M. Petersen 2

1Center for Basic Research in Digestive Diseases, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905
2Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 55905
3Division of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905
4Division of General Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905

email: Konstantinos N. Lazaridis (lazaridis.konstantinos@mayo.edu)

*Correspondence to Konstantinos N. Lazaridis, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905

Potential conflict of interest: Nothing to report.
fax: 507-284-0762

Funded by:
NIH; Grant Number: K23 DK68290
American Gastroenterological Association
Foundation for Digestive Health and Nutrition
American Liver Foundation
Palumbo Foundation
Miles and Shirley Fiterman Foundation
Mayo Clinic College of Medicine

Abstract

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disorder that can progress to cirrhosis, shortening life expectancy. PBC patients are often asymptomatic, present with biochemical cholestasis, and test positive (90%) for antimitochondrial antibodies (AMAs) in serum. Although AMA positivity without biochemical cholestasis may indicate increased risk of future PBC development, the contribution of these antibodies to pathogenesis remains enigmatic. Environmental risks and genetic determinants are likely implicated in PBC etiology. Given the familial aggregation of PBC, we hypothesized that AMAs also aggregate among relatives of PBC probands. We investigated the prevalence of AMAs in first-degree relatives (FDRs) of PBC probands to examine whether AMAs aggregate in such pedigrees. Using a PBC family registry, we prospectively screened for AMAs in the serum of 306 FDRs in 145 pedigrees, 350 PBC probands, and 196 controls who were age-matched, sex-matched, race-matched, and residence-matched to probands. The prevalence of AMA in FDRs and controls was 13.1% and 1%, respectively. Greater prevalence of AMA was found in female FDRs of PBC probands [sisters (20.7%), mothers (15.1%), and daughters (9.8%)] than in male FDRs [brothers (7.8%), fathers (3.7%), and sons (0%)]. Conclusions: AMAs aggregate among FDRs of PBC probands. Our data have clinical implications for FDRs of PBC probands because AMA positivity may suggest susceptibility to PBC. Thus, the identification and follow-up of these relatives may lead to earlier disease diagnosis and treatment. Furthermore, if AMA development is heritable, this trait will provide a basis to dissect the genetic predisposition to PBC. (HEPATOLOGY 2007.)