First Hospital, University of Jilin, Changchun, China.
Hepatology. 2012 May;55(5):1495-506. doi: 10.1002/hep.25511. Epub 2012 Apr 4.
Substantial evidence supports dysregulated B-cell immune responses in patients with primary biliary cirrhosis (PBC), including the presence of serum antimitochondrial antibodies (AMAs). However, recent reports from murine models of PBC suggest that B cells may also provide regulatory function, and indeed the absence of B cells in such models leads to exacerbation of disease. The vast majority of patients with PBC have readily detectable AMAs, but a minority (<5%) are AMA negative (AMA(-)), even with recombinant diagnostic technology. This issue prompted us to examine the nature of B-cell infiltrates surrounding the portal areas in AMA-positive (AMA(+)) and AMA(-) patients, because they display indistinguishable clinical features. Of importance was the finding that the degree of bile duct damage around the portal areas was significantly milder in AMA(+) PBC than those observed in AMA(-) PBC patients. The portal areas from AMA(-) patients had a significant increase of cluster of differentiation (CD)5(+) cells infiltrating the ductal regions, and the levels of B-cell infiltrates were worse in the early phase of bile duct damage. The frequency of positive portal areas and the magnitude of CD5(+) and CD20(+) cellular infiltrates within areas of ductal invasion is associated with the first evidence of damage of biliary duct epithelia, but becomes reduced in the ductopenia stage, with the exception of CD5(+) cells, which remain sustained and predominate over CD20(+) cells.
Our data suggest a putative role of B-cell autoimmunity in regulating the portal destruction characteristic of PBC.
大量证据表明原发性胆汁性肝硬化 (PBC) 患者的 B 细胞免疫反应失调，包括血清抗线粒体抗体 (AMA) 的存在。然而，来自 PBC 鼠模型的最新报告表明，B 细胞也可能提供调节功能，事实上，此类模型中 B 细胞的缺失会导致疾病恶化。绝大多数 PBC 患者都有可检测到的 AMA，但少数 (<5%) 为 AMA 阴性 (AMA(-))，即使使用重组诊断技术也是如此。这个问题促使我们检查 AMA 阳性 (AMA(+)) 和 AMA(-) 患者门脉周围 B 细胞浸润的性质，因为它们表现出无法区分的临床特征。重要的是发现，与 AMA(-) PBC 患者相比，AMA(+) PBC 患者门脉周围胆管损伤的程度明显较轻。AMA(-) PBC 患者的门脉区域有明显更多的 CD5(+)细胞浸润到胆管区域，并且在胆管损伤的早期阶段 B 细胞浸润程度更严重。阳性门脉区域的频率以及胆管浸润区域内 CD5(+)和 CD20(+)细胞的浸润程度与胆管上皮损伤的第一个证据相关，但在胆管减少阶段减少，除了 CD5(+)细胞，其持续存在并超过 CD20(+)细胞占主导地位。
我们的数据表明 B 细胞自身免疫在调节 PBC 的门脉破坏特征中具有潜在作用。
