Foureau D M, Walling T L, Maddukuri V, Anderson W, Culbreath K, Kleiner D E, Ahrens W A, Jacobs C, Watkins P B, Fontana R J, Chalasani N, Talwalkar J, Lee W M, Stolz A, Serrano J, Bonkovsky H L
Departments of Medicine, Surgery, Pathology, the Liver-Biliary-Pancreatic Center, Immune Monitoring Core Laboratory, Dickson Center for Advanced Analytics, Carolinas HealthCare System, Charlotte, USA.
Clin Exp Immunol. 2015 Apr;180(1):40-51. doi: 10.1111/cei.12558.
Drug-induced liver injury (DILI) is often caused by innate and adaptive host immune responses. Characterization of inflammatory infiltrates in the liver may improve understanding of the underlying pathogenesis of DILI. This study aimed to enumerate and characterize leucocytes infiltrating liver tissue from subjects with acute DILI (n = 32) versus non-DILI causes of acute liver injury (n = 25). Immunostains for CD11b/CD4 (Kupffer and T helper cells), CD3/CD20 (T and B cells) and CD8/CD56 [T cytotoxic and natural killer (NK) cells] were evaluated in biopsies from subjects with acute DILI, either immunoallergic (IAD) or autoimmune (AID) and idiopathic autoimmune (AIH) and viral hepatitis (VH) and correlated with clinical and pathological features. All biopsies showed numerous CD8(+) T cells and macrophages. DILI cases had significantly fewer B lymphocytes than AIH and VH and significantly fewer NK cells than VH. Prominent plasma cells were unusual in IAD (three of 10 cases), but were associated strongly with AIH (eight of nine) and also observed in most with AID (six of nine). They were also found in five of 10 cases with VH. Liver biopsies from subjects with DILI were characterized by low counts of mature B cells and NK cells in portal triads in contrast to VH. NK cells were found only in cases of VH, whereas AIH and VH both showed higher counts of B cells than DILI. Plasma cells were associated most strongly with AIH and less so with AID, but were uncommon in IAD.
药物性肝损伤（DILI）通常由宿主的先天性和适应性免疫反应引起。对肝脏炎症浸润的特征进行分析可能有助于加深对DILI潜在发病机制的理解。本研究旨在对急性DILI患者（n = 32）与急性肝损伤非DILI病因患者（n = 25）肝脏组织中浸润的白细胞进行计数和特征分析。对急性DILI患者（包括免疫过敏性DILI（IAD）、自身免疫性DILI（AID）、特发性自身免疫性肝炎（AIH）和病毒性肝炎（VH））的活检组织进行了CD11b/CD4（库普弗细胞和辅助性T细胞）、CD3/CD20（T细胞和B细胞）以及CD8/CD56 [细胞毒性T细胞和自然杀伤（NK）细胞]免疫染色，并与临床和病理特征进行关联分析。所有活检组织均显示有大量CD8(+) T细胞和巨噬细胞。DILI病例的B淋巴细胞明显少于AIH和VH，NK细胞明显少于VH。显著的浆细胞在IAD中不常见（10例中有3例），但与AIH密切相关（9例中有8例），在大多数AID病例中也可观察到（9例中有6例）。在10例VH病例中有5例也发现了浆细胞。与VH相比，DILI患者的肝活检组织特征为门三联中成熟B细胞和NK细胞数量较少。NK细胞仅在VH病例中发现，而AIH和VH的B细胞计数均高于DILI。浆细胞与AIH关联最为密切，与AID的关联较弱，但在IAD中不常见。
