Duthie A, Doherty D G, Donaldson P T, Scott-Jupp R, Tanner M S, Eddleston A L, Mowat A P
Department of Child Health, King's College Hospital Medical School, London, UK.
J Hepatol. 1995 Nov;23(5):532-7. doi: 10.1016/0168-8278(95)80058-1.
BACKGROUND/AIMS: Chronic liver disease is a well-recognised complication of cystic fibrosis. Recent reports suggest that its development is not determined by specific mutations within the cystic fibrosis gene; however, familial clustering of portal hypertension cases and inappropriate immune responses against liver membrane antigens demonstrated in children with cystic fibrosis and chronic liver disease suggest that other genetic loci may be relevant. As the major histocompatibility complex has an important immunoregulatory role, we have investigated for associations with this complex and chronic liver disease in cystic fibrosis.
We have determined human leucocyte antigen class I (A and B) and class II (DR) phenotypes by serological tissue typing and class II (DR and DQ) and class III (complement component C4 and 21-hydroxylase) gene polymorphisms in 274 children and young adults with cystic fibrosis, of whom 82 had evidence of chronic liver disease with portal hypertension in 49, and 146 healthy controls.
A marked difference in human leucocyte antigen frequency was limited to DQ6, which was found in 66.7% of cystic fibrosis patients with liver disease compared to 32.9% of patients with no liver disease (Pc < 0.03) and 28.8% of controls (Pc < 0.006). An increased frequency of the two antigens in strong linkage disequilibrium with DQ6 was also observed within this patient group, namely DR15 and B7. When the patients were stratified for the presence of portal hypertension, these observations were confirmed, but the human leucocyte antigen associations were significant only for male patients and there was no association with the age of onset of liver disease.
These data suggest that the haplotype B7-DR15-DQ6 may carry an increased risk of development of liver disease in male cystic fibrosis patients.
背景/目的：慢性肝病是囊性纤维化一种公认的并发症。近期报告表明，其发展并非由囊性纤维化基因内的特定突变所决定；然而，囊性纤维化和慢性肝病患儿中门静脉高压病例的家族聚集现象以及针对肝细胞膜抗原的不适当免疫反应表明，其他基因位点可能与之相关。由于主要组织相容性复合体具有重要的免疫调节作用，我们研究了其与囊性纤维化慢性肝病之间的关联。
我们通过血清学组织分型确定了274例囊性纤维化儿童和青年的人类白细胞抗原I类（A和B）和II类（DR）表型，以及II类（DR和DQ）和III类（补体成分C4和21 - 羟化酶）基因多态性，其中82例有慢性肝病证据，49例有门静脉高压，另有146例健康对照。
人类白细胞抗原频率的显著差异仅限于DQ6，在患有肝病的囊性纤维化患者中，DQ6的出现频率为66.7%，而无肝病患者为32.9%，对照为28.8%（Pc < 0.03）（Pc < 0.006）。在该患者组中还观察到与DQ6处于强连锁不平衡状态的两种抗原频率增加，即DR15和B7。当根据门静脉高压的存在对患者进行分层时，这些观察结果得到证实，但人类白细胞抗原关联仅在男性患者中具有统计学意义，且与肝病发病年龄无关。
这些数据表明，单倍型B7 - DR15 - DQ6可能使男性囊性纤维化患者患肝病的风险增加。
