Department of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
First Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Hepatol Commun. 2023 Apr 26;7(5). doi: 10.1097/HC9.0000000000000123. eCollection 2023 May 1.
Variant syndromes of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) share diagnostic features of both entities, but their immunological underpinnings remain largely unexplored.
We performed blood profiling of 23 soluble immune markers and immunogenetics in a cohort of 88 patients with autoimmune liver diseases (29 typical AIH, 31 typical PBC and 28 with clinically PBC/AIH variant syndromes). The association with demographical, serological and clinical features was analyzed.
While T and B cell receptor repertoires were highly skewed in variant syndromes compared to healthy controls, these biases were not sufficiently discriminated within the spectrum of autoimmune liver diseases. High circulating checkpoint molecules sCD25, sLAG-3, sCD86 and sTim-3 discriminated AIH from PBC on top of classical parameters such as transaminases and immunoglobulin levels. In addition, a second cluster of correlated soluble immune factors encompassing essentially TNF, IFNγ, IL12p70, sCTLA-4, sPD-1 and sPD-L1 appeared characteristic of AIH. Cases with complete biochemical responses to treatment generally showed a lower level of dysregulation. Unsupervised hierarchical clustering of classical and variant syndromes identified two pathological immunotypes consisting predominantly of either AIH or PBC cases. Variant syndromes did not form a separate group, but clustered together with either classical AIH or PBC. Clinically, patient with AIH-like variant syndromes were less likely to be able discontinue immunosuppressive treatment.
Our analyses suggest that variants of immune mediated liver diseases may represent an immunological spectrum from PBC to AIH-like disease reflected by their pattern of soluble immune checkpoint molecules rather than separate entities.
自身免疫性肝炎（AIH）和原发性胆汁性胆管炎（PBC）的变异综合征具有这两种疾病的共同诊断特征，但它们的免疫学基础仍在很大程度上尚未得到探索。
我们对 88 例自身免疫性肝病患者（29 例典型 AIH、31 例典型 PBC 和 28 例具有临床 PBC/AIH 变异综合征）进行了 23 种可溶性免疫标志物和免疫遗传学的血液分析。分析了其与人口统计学、血清学和临床特征的相关性。
虽然变异综合征中的 T 和 B 细胞受体库与健康对照组相比存在高度偏倚，但在自身免疫性肝病的范围内，这些偏差并没有得到充分区分。高循环检查点分子 sCD25、sLAG-3、sCD86 和 sTim-3 在包括转氨酶和免疫球蛋白水平等经典参数的基础上，将 AIH 与 PBC 区分开来。此外，一个包含 TNF、IFNγ、IL12p70、sCTLA-4、sPD-1 和 sPD-L1 等基本因子的相关可溶性免疫因子的第二簇，是 AIH 的特征。对治疗有完全生化反应的病例通常表现出较低的失调水平。对经典和变异综合征的无监督层次聚类确定了两种主要由 AIH 或 PBC 病例组成的病理免疫类型。变异综合征并未形成单独的组，而是与经典 AIH 或 PBC 聚类在一起。临床上，AIH 样变异综合征患者更不可能停止免疫抑制治疗。
我们的分析表明，免疫介导的肝病变异可能代表了从 PBC 到 AIH 样疾病的免疫谱，这反映在其可溶性免疫检查点分子的模式上，而不是单独的实体。
