Thomsen Christian, Birkelund Svend, Røge Rasmus
Department of Pathology, Aalborg University Hospital, Aalborg, Denmark.
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
APMIS. 2025 Jun;133(6):e70034. doi: 10.1111/apm.70034.
Thomsen C, Birkelund S, Røge R. Immunohistochemical profiling of interferon-stimulated genes in histopathological specimens: A potential screening approach for viral infections. Identifying viral infections in histopathological specimens can pose a diagnostic challenge. Increased expression of interferon-stimulated genes (ISGs) may serve as a potential screening marker for such infections. This study undertakes a comparative analysis of ISG immunohistochemical expression in various tissue types, encompassing both normal and inflamed tissues, including both viral and nonviral etiologies. Archival formalin-fixed paraffin-embedded (FFPE) tissues with confirmed viral infection (n = 27) and nonviral inflammation (n = 15) were analyzed. Tissue microarrays (TMAs) were constructed and stained with antibodies against ISGs: Human myxovirus resistance protein 1 (MxA), RIG-I, MDA5, PKR, and PD-L1. Qualitative assessment compared their upregulation to five normal controls of each tissue type. MxA exhibited significantly increased upregulation in viral infections compared to nonviral inflammation (OR 6.53 [CI 1.59, 26.79]), with sensitivity and specificity of 0.70 (0.50, 0.86) and 0.73 (0.45, 0.92), respectively. The remaining ISGs showed no significant differences and had moderate sensitivity and low specificity. In conclusion, while MxA, PD-L1, PKR, MDA5, and RIG-I generally showed upregulation in most viral infections, variability was observed. MxA holds promise as a viral infection screening marker in FFPE samples, but its utility may be limited by an inadequate interferon response to certain viruses.
汤姆森 C、比尔克伦德 S、勒厄 R。组织病理学标本中干扰素刺激基因的免疫组织化学分析：一种潜在的病毒感染筛查方法。在组织病理学标本中识别病毒感染可能带来诊断挑战。干扰素刺激基因（ISG）表达增加可能作为此类感染的潜在筛查标志物。本研究对各种组织类型（包括正常组织和炎症组织，涵盖病毒和非病毒病因）中 ISG 的免疫组织化学表达进行了比较分析。分析了经证实有病毒感染的存档福尔马林固定石蜡包埋（FFPE）组织（n = 27）和非病毒炎症组织（n = 15）。构建了组织微阵列（TMA），并用针对 ISG 的抗体进行染色：人黏液病毒抗性蛋白 1（MxA）、视黄酸诱导基因 I（RIG-I）、黑色素瘤分化相关蛋白 5（MDA5）、蛋白激酶 R（PKR）和程序性死亡受体配体 1（PD-L1）。定性评估将它们的上调情况与每种组织类型的五个正常对照进行比较。与非病毒炎症相比，MxA 在病毒感染中的上调显著增加（比值比 6.53 [可信区间 1.59，26.79]），敏感性和特异性分别为 0.70（0.50，0.86）和 0.73（0.45，0.92）。其余的 ISG 没有显著差异，敏感性中等，特异性较低。总之，虽然 MxA、PD-L1、PKR、MDA5 和 RIG-I 在大多数病毒感染中通常表现出上调，但存在变异性。MxA 有望作为 FFPE 样本中病毒感染的筛查标志物，但其效用可能受到对某些病毒的干扰素反应不足的限制。
