Comparative studies of antimitochondrial autoantibodies in sera and bile in primary biliary cirrhosis
Comparative studies of antimitochondrial autoantibodies in sera and bile in primary biliary cirrhosis
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DOI：
10.1002/hep.510250506
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发表时间：
1997-05-01
期刊：
影响因子：
13.5
通讯作者：
Gershwin, ME
中科院分区：
文献类型：
--
作者：
Nishio, A;VandeWater, J;Gershwin, ME
原发性胆汁性肝硬化（PBC）是一种以肝内胆管破坏为特征的自身免疫性肝病，虽然该病的发病机制尚不清楚，但早前在患者血清中就发现了高滴度的抗线粒体自身抗体（AMA），然而，对AMA在胆汁中的存在知之甚少，在本研究中，我们调查了PBC患者和健康对照者的胆汁和血清中是否存在AMA和线粒体自身抗原。19例PBC患者中有17例（89.4%）在胆汁中检测到AMA；19例患者中有15例（78.9%）特异性针对丙酮酸脱氢酶复合物（PDC-E2）， 19例患者中有6例（31.6%）特异性针对支链2-氧酸脱氢酶复合物E2 (BCOADC-E2)， 19例患者中有1例（5.3%）特异性针对2-氧乙酸脱氢酶复合物E2 （OGDC-E2）。在同一患者血清的比较研究中，19例患者中有19例（100%）发现抗PDC-E2抗体，19例患者中有9例（47.3%）发现抗bcoadc抗体。19例PBC患者中有9例（47.7%）在胆汁中发现AMA，其中4例（21.1%）在胆汁中发现AMA，同时在同一患者的血清中发现相应特异性的抗体；19例患者中有8例（42.1%）特异性针对PDC-E2, 19例患者中有2例（10.5%）特异性针对BCOADC。IgA抗PDC-E2抗体的表位定位表明，与血清自身抗体一样，免疫优势表位针对PDC-E2的内脂酰结构域。血清中IgA AMA的患病率和抗原反应性与胆汁中IgA AMA完全相关。8例PBC患者血清中有1例（12.5%）发现抗核包膜孔蛋白（gp210）的自身抗体，但在胆汁中未发现。此外，特别有趣的是，我们分别在19例患者中的12例（63.2%）、19例患者中的9例（47.4%）和19例患者中的9例（47.4%）的胆汁中检测到自身抗原PDC-E2、OGDC-E2和ECOADC-E2；虽然胆汁中AMA的存在可能仅仅反映了血清中这些抗体的存在，但胆汁中线粒体自身抗原的同时检测表明炎症部位线粒体自身抗原的增加，这种自身抗原与AMA结合，可能会增强局部免疫反应和疾病进展。
Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by destruction of intrahepatic bile ducts, Although the pathogenesis of this disease is still unknown, high titers of antimitochondrial autoantibodies (AMA) have long been recognized in patient sera, However, little is known about the presence of AMA in bile, In this study, we investigated bile and sera from patients with PBC and healthy controls for the presence of AMA and mitochondrial autoantigens, AMA were detected in the bile of 17 of 19 patients (89.4%) with PBC; they were specifically directed against the pyruvate dehydrogenase complex (PDC-E2) in 15 of 19 patients (78.9%), to the branched-chain 2-oxo-acid dehydrogenase complex E2 (BCOADC-E2) in 6 of 19 patients (31.6%), and to the 2-oxoglutarate dehydrogenase complex E2 (OGDC-E2) in 1 of 19 patients (5.3%), In a comparative study of sera from the same patients, anti-PDC-E2 antibodies were found in 19 of 19 patients (100%), anti-BCOADC in 9 of 19 patients (47.3%), and anti-OGDC-E2 in 4 of 19 patients (21.1%) patients, AMA in bile were always found together with antibodies of corresponding specificities in the serum from the same patient, Immunoglobulin (Ig)A AMA mere found in the bile of 9 of 19 patients (47.7%) with PBC; they were specifically directed against PDC-E2 in 8 of 19 patients (42.1%) and to BCOADC in 2 of 19 patients (10.5%), Epitope mapping of IgA anti-PDC-E2 antibodies indicated that, like serum autoantibodies, the immunodominant epitope is directed against the inner lipoyl domain of PDC-E2, The prevalence and antigen reactivity of IgA AMA in sera correlated completely with IgA AMA in bile, Autoantibodies against nuclear envelope pore proteins (gp210) were found in 1 of 8 (12.5%) sera of patients with PBC, but not in bile. Furthermore, and of particular interest, we detected the autoantigens, PDC-E2, OGDC-E2, and ECOADC-E2, in the bile of 12 of 19 patients (63.2%), 9 of 19 patients (47.4%), and 9 of 19 patients (47.4%), respectively; PDC-E2 was found in only 1 of 17 (5.9%) disease controls, Although the presence of AMA in bile may merely reflect the presence of these antibodies in sera, the simultaneous detection of mitochondrial autoantigens in bile suggests an increase of mitochondrial autoantigens at inflammatory sites, Such autoantigens, coupled with AMA, may augment the local immune response and disease progression.