Quaranta S, Shulman H, Ahmed A, Shoenfeld Y, Peter J, McDonald G B, Van de Water J, Coppel R, Ostlund C, Worman H J, Rizzetto M, Tsuneyama K, Nakanuma Y, Ansari A, Locatelli F, Paganin S, Rosina F, Manns M, Gershwin M E
University of California, Davis 95616-8660, USA.
Clin Immunol. 1999 Apr;91(1):106-16. doi: 10.1006/clim.1998.4666.
Primary biliary cirrhosis (PBC) and graft-versus-host disease (GVHD) are thought to have common immunopathologic features and previous studies have reported that 5.2 to 81% of patients with chronic GVHD after allogeneic hematopoietic cell transplant have antimitochondrial antibodies (AMA). We studied a total of 89 patients with chronic GVHD and 60 controls for AMA reactivity by ELISA and immunoblotting using recombinant PDC-E2, BCOADC-E2, and OGDC-E2, immunoblotting of beef heart mitochondrial proteins, and reactivity to nuclei, smooth muscle (ASMA), ribonucleoprotein JO-1, extractable nuclear antigen, nuclear proteins SSA/ SSB, ribonucleic P proteinase III, cardiolipin (ACA), liver kidney microsomal, thyroid microsomal, myeloperoxidase, and the reactivity of rheumatoid factor. A subset of 60 chronic GVHD sera were tested for reactivity to gp210 and LBR. Finally, liver tissue from patients with chronic GVHD and PBC was studied by immunohistochemistry to determine whether there was comparable abnormal apical staining of biliary epithelial cells using PDC-E2-specific monoclonal antibodies. Surprisingly, there were no AMA found in the sera from the 89 patients with chronic GVHD. Review of published data on AMA in GVHD suggests that previous results were primarily false positives. In contrast, sera from the patients with GVHD did have a variety of other autoantibodies and, in particular, 20/89 (22.4%) positive ANA, 23/89 (25.8%) positive ASMA, and 9/89 (10.1%) positive ACA. The other autoantibodies assayed were not statistically different from controls. Finally, abnormal biliary epithelial luminal staining of bile ducts was found, as expected, in liver tissue of patients with PBC but was absent in chronic GVHD.
原发性胆汁性肝硬化（PBC）和移植物抗宿主病（GVHD）被认为具有共同的免疫病理特征，先前的研究报道，异基因造血细胞移植后慢性GVHD患者中有5.2%至81%存在抗线粒体抗体（AMA）。我们通过酶联免疫吸附测定（ELISA）和免疫印迹法，使用重组丙酮酸脱氢酶二聚体-E2（PDC-E2）、二氢硫辛酸琥珀酰转移酶-E2（BCOADC-E2）和鸟氨酸氨基甲酰转移酶-E2（OGDC-E2），对89例慢性GVHD患者和60例对照进行AMA反应性研究，还进行了牛心肌线粒体蛋白免疫印迹，以及对细胞核、平滑肌（抗平滑肌抗体，ASMA）、核糖核蛋白JO-1、可提取核抗原、核蛋白SSA/SSB、核糖核酸酶III、心磷脂（抗心磷脂抗体，ACA）、肝肾微粒体、甲状腺微粒体、髓过氧化物酶的反应性，以及类风湿因子的反应性研究。对其中60份慢性GVHD血清的一个亚组检测了其对糖蛋白210（gp210）和板层素结合受体（LBR）的反应性。最后，通过免疫组织化学研究慢性GVHD患者和PBC患者的肝组织，以确定使用PDC-E2特异性单克隆抗体时，胆管上皮细胞的顶端染色异常是否具有可比性。令人惊讶的是，在89例慢性GVHD患者的血清中未发现AMA。对已发表的关于GVHD中AMA的数据回顾表明，先前的结果主要是假阳性。相比之下，GVHD患者的血清确实有多种其他自身抗体，特别是，20/89（22.4%）抗核抗体（ANA）阳性，23/89（25.8%）抗平滑肌抗体阳性，9/89（10.1%）抗心磷脂抗体阳性。所检测的其他自身抗体与对照组无统计学差异。最后，正如预期的那样，在PBC患者的肝组织中发现胆管的胆管上皮管腔染色异常，但在慢性GVHD中未发现。
