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移植肾活检后第一年的肾小球炎症:细胞类型与抗体介导的排斥反应和移植物结局的关系。

Glomerular inflammation in renal allografts biopsies after the first year: cell types and relationship with antibody-mediated rejection and graft outcome.

机构信息

Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.

出版信息

Transplantation. 2010 Dec 27;90(12):1478-85. doi: 10.1097/TP.0b013e3181ff87f5.

DOI:10.1097/TP.0b013e3181ff87f5
PMID:21042235
Abstract

BACKGROUND

Antibody-mediated rejection manifests with glomerular and peritubular capillary inflammation and transplant glomerulopathy (TG). The role of glomerular inflammation (GI) components in the development of TG and their impact on outcome are incompletely understood.

METHODS

GI was quantified on hematoxylin-eosin, CD3, CD20, and CD68 stains on biopsies from 240 patients with grafts functioning more than or equal to 1 year.

RESULTS

A predominance of CD68+ cells followed by less numerous CD3+ cells was found in TG and glomerulitis. CD68+ cells more than 12 in the most inflamed glomerulus were strongly associated with TG, donor-specific antibody (DSA), and C4d staining. Glomerular CD68+ cells correlated with peritubular capillary multilamellation, and similarly, the Banff g score correlated with light and electron microscopic indexes of chronic microvascular damage. Overall, GI components correlated with the g score, DSA, and peritubular capillary C4d+. The Banff cg 1, 2, and 3 scores showed high levels of GI composed mostly of CD68+ cells, similar to but not higher than cases of g2 and g3 glomerulitis. Glomerular T cells and neutrophils followed similar trends as the predominant macrophages. T-cell-mediated rejection in this cohort did not significantly affect the composition of GI. Prognostically, all types of pronounced GI, g scores, DSA+, C4d+, and capillaropathy were associated with worse prognosis; however, only high level of macrophages was an independent predictor of graft failure.

CONCLUSIONS

GI in more than or equal to 1 year grafts is mostly antibody-mediated rejection related, correlates with chronic microvascular damage, and consists predominantly of macrophages. The latter seem to represent a pivotal pathogenetic, diagnostic, and prognostic factor in this setting.

摘要

背景

抗体介导的排斥反应表现为肾小球和肾小管毛细血管炎症以及移植肾小球病(TG)。肾小球炎症(GI)成分在 TG 发展中的作用及其对结局的影响尚不完全清楚。

方法

在 240 例移植后功能超过或等于 1 年的患者的活检标本上,用苏木精-伊红、CD3、CD20 和 CD68 染色定量评估 GI。

结果

在 TG 和肾小球肾炎中发现 CD68+细胞占主导地位,其次是数量较少的 CD3+细胞。在最炎症的肾小球中超过 12 个的 CD68+细胞与 TG、供体特异性抗体(DSA)和 C4d 染色强烈相关。肾小球 CD68+细胞与肾小管毛细血管多层化相关,同样,Banff g 评分与慢性微血管损伤的光镜和电子显微镜指标相关。总体而言,GI 成分与 g 评分、DSA 和肾小管毛细血管 C4d+相关。Banff cg1、2 和 3 评分显示高水平的 GI,主要由 CD68+细胞组成,与 g2 和 g3 肾小球肾炎相似但不高于后者。肾小球 T 细胞和中性粒细胞与主要的巨噬细胞相似,呈类似趋势。在本队列中,T 细胞介导的排斥反应并未显著影响 GI 的组成。在预后方面,所有类型的明显 GI、g 评分、DSA+、C4d+和毛细血管病变均与预后较差相关;然而,只有高水平的巨噬细胞是移植失败的独立预测因素。

结论

1 年以上移植的 GI 主要与抗体介导的排斥反应有关,与慢性微血管损伤相关,主要由巨噬细胞组成。在后一种情况下,它们似乎代表了这种情况下的关键发病机制、诊断和预后因素。

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