Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
Division of Pathology, Nippon Medical School Hospital, Tokyo, Japan.
BMC Nephrol. 2023 Mar 9;24(1):48. doi: 10.1186/s12882-023-03091-8.
Immune checkpoint inhibitors (ICIs) have provided significant benefits in cancer treatment, but they could develop immune-related adverse events (irAE). ICI-associated renal adverse effects are rare and tubulointerstitial nephritis (TIN) is the most common in the renal irAE. However, only a few case reports of renal vasculitis associated with ICI have been reported. In addition, the characteristics of infiltrating inflammatory cells of ICI-associated TIN and renal vasculitis have been uncertain.
A 65-year-old man received immune checkpoint inhibitors (ICIs), anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) and anti-PD-1 (programmed cell death 1) antibodies for aggravated metastatic malignant melanoma. About 1 week after the second administration of nivolumab and ipilimumab, acute kidney injury developed. A renal biopsy was performed that showed TIN and non-necrotizing granulomatous vasculitis in interlobular arteries. Massive CD3 T cells and CD163 macrophages infiltrated both tubulointerstitium and interlobular arteries. Many infiltrating cells tested positive for Ki-67 and PD-1 ligand (PD-L1), but negative for PD-1. In CD3 T cells, CD8 T cells were predominantly infiltrated, and these cells were positive for Granzyme B (GrB) and cytotoxic granule TIA-1, but negative for CD25, indicating antigen-independent activated CD8 T cells. Infiltration of CD4 T cells was noted without obvious CD4 CD25 regulatory T (Treg) cells. His renal dysfunction recovered within 2 months of treatment with prednisolone in addition to discontinuation of nivolumab and ipilimumab.
We herein reported a case of ICI-related TIN and renal granulomatous vasculitis with infiltration of massive antigen-independent activated CD8 T cells and CD163 macrophages, and none or few CD4 CD25 Treg cells. These infiltrating cells might be a characteristic of the development of renal irAE.
免疫检查点抑制剂（ICI）在癌症治疗中带来了显著的获益，但它们可能引发免疫相关不良反应（irAE）。ICI 相关的肾不良反应较为罕见，其中小管间质性肾炎（TIN）最为常见。然而，仅有少数与 ICI 相关的肾血管炎病例报告。此外，ICI 相关 TIN 和肾血管炎浸润性炎症细胞的特征尚不确定。
一名 65 岁男性因转移性恶性黑色素瘤加重而接受免疫检查点抑制剂（ICI）、抗 CTLA-4（细胞毒性 T 淋巴细胞相关蛋白 4）和抗 PD-1（程序性细胞死亡 1）抗体治疗。在接受纳武利尤单抗和伊匹单抗第二次给药后约 1 周，发生急性肾损伤。进行了肾活检，结果显示 TIN 和小叶间动脉的非坏死性肉芽肿性血管炎。大量 CD3 T 细胞和 CD163 巨噬细胞浸润于肾小管间质和小叶间动脉。大量浸润细胞 Ki-67 和 PD-1 配体（PD-L1）阳性，但 PD-1 阴性。在 CD3 T 细胞中，主要浸润 CD8 T 细胞，这些细胞 Granzyme B（GrB）和细胞毒性颗粒 TIA-1 阳性，而 CD25 阴性，提示抗原非依赖性激活的 CD8 T 细胞。观察到 CD4 T 细胞浸润，但无明显的 CD4 CD25 调节性 T（Treg）细胞。在停用纳武利尤单抗和伊匹单抗的同时，加用泼尼松龙治疗后，他的肾功能在 2 个月内恢复。
我们在此报告了一例 ICI 相关的 TIN 和肾肉芽肿性血管炎，浸润大量抗原非依赖性激活的 CD8 T 细胞和 CD163 巨噬细胞，而无或很少有 CD4 CD25 Treg 细胞。这些浸润细胞可能是肾 irAE 发展的特征。
