Lymphocyte aggregates persist and accumulate in the lungs of patients with idiopathic pulmonary fibrosis.
Lymphocyte aggregates persist and accumulate in the lungs of patients with idiopathic pulmonary fibrosis.
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DOI：
10.2147/jir.s40673
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发表时间：
2013
影响因子：
4.5
通讯作者：
Atamas SP
中科院分区：
文献类型：
--
作者：
Todd NW;Scheraga RG;Galvin JR;Iacono AT;Britt EJ;Luzina IG;Burke AP;Atamas SP
特发性肺纤维化（IPF）是一种致命的肺部疾病，目前尚无有效的治疗方法。通常认为，肺部炎症随着IPF的进展而消退，但尚未得到客观评价。这项工作的目的是评估炎症细胞浸润程度的变化，特别是淋巴细胞浸润，在疾病期间IPF。在疾病早期进行外科肺活检（SLB）的患者和晚期疾病随后进行肺移植的患者中，确定了16例确诊的IPF患者。采用数值评分系统从组织学上量化每个SLB和肺移植组织样本中纤维化、蜂窝变化、成纤维细胞灶和淋巴细胞聚集的数量。通过比较配对、匹配的SLB样本与肺移植组织进行定量评分分析。从SLB到肺移植的中位时间[1、3四分位数]为24[15,29]个月。与SLB相比，外植体样品的组织学纤维化和蜂窝状变化更为明显（P < 0.001和P < 0.01），最值得注意的是，外植体样品中淋巴细胞聚集体的数量高于SLB （P = 0.013）。免疫组织化学分析显示，聚集物中含有丰富的CD3+ （T淋巴细胞）和CD20+ （B淋巴细胞）细胞，但没有CD68+（巨噬细胞）细胞。与通常的假设相反，与早期疾病（外科肺活检）相比，晚期疾病（外植组织）中淋巴细胞聚集物的数量更多。这一发现表明，即使在严重的终末期疾病中，IPF中活跃的细胞炎症仍在继续。
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with no known effective therapy. It is often assumed, but has not been objectively evaluated, that pulmonary inflammation subsides as IPF progresses. The goal of this work was to assess changes in the degree of inflammatory cell infiltration, particularly lymphocytic infiltration, over the duration of illness in IPF. Sixteen patients with confirmed IPF were identified in patients whom surgical lung biopsy (SLB) was performed in early disease, and in patients whom lung transplantation was subsequently performed in end stage disease. A numerical scoring system was used to histologically quantify the amount of fibrosis, honeycomb change, fibroblastic foci, and lymphocyte aggregates in each SLB and lung explant tissue sample. Analyses of quantitative scores were performed by comparing paired, matched samples of SLB to lung explant tissue. Median time [1st, 3rd quartiles] from SLB to lung transplantation was 24 [15, 29] months. Histologic fibrosis and honeycomb change were more pronounced in the explant samples compared with SLB (P < 0.001 and P < 0.01, respectively), and most notably, higher numbers of lymphocyte aggregates were observed in the explant samples compared to SLB (P = 0.013). Immunohistochemical analyses revealed abundant CD3+ (T lymphocyte) and CD20+ (B lymphocyte) cells, but not CD68+ (macrophage) cells, within the aggregates. Contrary to the frequent assumption, lymphocyte aggregates were present in greater numbers in advanced disease (explant tissue) compared to early disease (surgical lung biopsy). This finding suggests that active cellular inflammation continues in IPF even in severe end stage disease.