Mass COVID-19 vaccination programs in kidney transplant patients (KTRs) have demonstrated an excellent safety profile, without increased rates of ensuing alloimmune events. However, autoimmune diseases may seldom occur after vaccination. We report the case of a KTR who presented de novo posttransplant membranous nephropathy (MN) following administration of COVID-19 vaccine.

A 66-year-old patient underwent first kidney transplantation for autosomal-dominant polycystic-kidney-disease-related end-stage kidney disease in June 2020. His medical history included hypertension and left nephrectomy in 2016. After basiliximab induction, the maintenance regimen consisted of tacrolimus, mycophenolic acid, and steroids. His baseline creatinine level was 100 μmol/L, and he remained free of proteinuria during the posttransplant course. A 3-month protocol graft biopsy was unremarkable. Immunohistochemistry (IHC) C4d staining was negative (Figure 1A,B).

The patient received the second injection of the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech) in March 2021. Subsequent serology tests showed negative results, consistent with a blunted antibody response to the vaccine, as widely reported in KTRs.

Eight weeks after the second vaccine dose, the patient underwent a 1-year protocol graft biopsy. Concurrent creatinine level and proteinuria were 120 μmol/L and negative, respectively. Light microscopy showed normal glomeruli and ruled out subclinical rejection(Figure 1D). However, C4d staining revealed the presence of granular staining along the glomerular basement membrane consistent with stage 1 MN (Figure 1E). Anti-phospholipase-A2-receptor (PLA2R) immunochemistry analysis showed strong positive staining on the glomerular capillary walls (Figure 1F). Circulating PLA2R antibodies were negative. Notably, IHC staining for PLA2R and C4d was retrospectively negative in the 3-month protocol graft biopsy (Figure 1E) and in the native kidney specimen (nephrectomy). The residual renal parenchyma on the native kidney contained non-sclerotic glomeruli. We retrospectively performed Jones staining which did not show irregularities of the glomerular basement membrane suggestive of membranous nephropathy. There was no available frozen sample on the renal parenchyma. Hence, the diagnosis of de novo posttransplant MN was firmly established. Screening for malignancy and infections remained negative, excluding secondary causes of MN. COVID-19 tests remained also negative (SARS-CoV-2 PCR was negative at MN diagnosis and 3 months after the diagnosis. Anti-Spike IgG were negative 1 and 2 months after the diagnosis).

This is the first case of de novo posttransplant MN following mRNA COVID-19 vaccine. Interestingly, cases of de novo or relapsing MN after COVID-19 vaccine have recently been reported.^1-3 Additionally, rare cases of MN (including one PLA2R+ case) have been described after COVID-19 infection.⁴

The temporality between COVID-19 vaccination and PLA2R+ MN in a patient without history of MN and in whom the etiological workup has remained otherwise negative, supports a causal link. However, we must acknowledge that a coincidental association could not be ruled out.

Given the lack of proteinuria, no specific treatment was introduced. The subclinical presentation of MN may be related to the mitigating effects of maintenance immunosuppressive therapy.

In conclusion, auto-immune reactivity and MN may occur after mRNA COVID-19 vaccine. This report will raise awareness of nephrologists for the need to closely monitor patients with primary MN, following COVID-19 vaccination, including KTRs. If proteinuria occurs after vaccination, a graft biopsy should be promptly performed to firmly establish the diagnosis.

肾移植患者 (KTR) 的大规模 COVID-19 疫苗接种计划已证明具有出色的安全性，并且没有增加随后发生同种免疫事件的发生率。但是，自身免疫性疾病很少会在接种疫苗后发生。我们报告了一名 KTR 患者在接种 COVID-19 疫苗后出现新发移植后膜性肾病 (MN) 的病例。

一名 66 岁的患者于 2020 年 6 月因常染色体显性多囊肾病相关的终末期肾病接受了首次肾移植。他的病史包括高血压和 2016 年的左肾切除术。在巴利昔单抗诱导后，维持方案包括他克莫司、麦考酚酸和类固醇。他的基线肌酐水平为 100 μmol/L，并且他在移植后过程中保持无蛋白尿。3 个月的方案移植物活检无异常。免疫组织化学 (IHC) C4d 染色呈阴性（图 1A、B）。

该患者于 2021 年 3 月接受了 BNT162b2 mRNA COVID-19 疫苗（Pfizer-BioNTech）的第二次注射。随后的血清学测试显示阴性结果，这与 KTR 中广泛报道的疫苗抗体反应减弱一致。

第二次疫苗接种后 8 周，患者接受了为期 1 年的方案移植物活检。同时肌酐水平和蛋白尿分别为 120 μmol/L 和阴性。光学显微镜显示正常肾小球并排除亚临床排斥反应（图 1D）。然而，C4d 染色显示沿肾小球基底膜存在颗粒染色，与 1 期 MN 一致（图 1E）。抗磷脂酶 A2 受体 (PLA2R) 免疫化学分析显示肾小球毛细血管壁呈强阳性染色（图 1F）。循环 PLA2R 抗体呈阴性。值得注意的是，PLA2R 和 C4d 的 IHC 染色在 3 个月的方案移植物活检（图 1E）和天然肾脏标本（肾切除术）中回顾性呈阴性。本机肾上残留的肾实质含有非硬化性肾小球。我们回顾性地进行了琼斯染色，未显示提示膜性肾病的肾小球基底膜不规则。肾实质上没有可用的冷冻样本。因此，新发移植后 MN 的诊断确立。恶性肿瘤和感染筛查仍为阴性，排除了 MN 的继发性病因。COVID-19 检测也保持阴性（SARS-CoV-2 PCR 在 MN 诊断时和诊断后 3 个月呈阴性。抗刺突 IgG 在诊断后 1 个月和 2 个月呈阴性）。恶性肿瘤和感染筛查仍为阴性，排除了 MN 的继发性病因。COVID-19 检测也保持阴性（SARS-CoV-2 PCR 在 MN 诊断时和诊断后 3 个月呈阴性。抗刺突 IgG 在诊断后 1 个月和 2 个月呈阴性）。恶性肿瘤和感染筛查仍为阴性，排除了 MN 的继发性病因。COVID-19 检测也保持阴性（SARS-CoV-2 PCR 在 MN 诊断时和诊断后 3 个月呈阴性。抗刺突 IgG 在诊断后 1 个月和 2 个月呈阴性）。

这是第一例在接种 mRNA COVID-19 疫苗后新发的移植后 MN。有趣的是，最近报道了 COVID-19 疫苗接种后新发或复发性 MN 病例。^1-3此外，在 COVID-19 感染后描述了罕见的 MN 病例（包括一例 PLA2R+ 病例）。^4个

COVID-19 疫苗接种与 PLA2R+ MN 在没有 MN 病史且病原学检查仍为阴性的患者之间的时间性支持因果关系。然而，我们必须承认，不能排除巧合的关联。

鉴于没有蛋白尿，未引入特殊治疗。MN 的亚临床表现可能与维持免疫抑制治疗的缓解作用有关。

总之，自身免疫反应和MN可能发生在mRNA COVID-19疫苗接种后。这份报告将提高肾病学家的认识，让他们意识到在接种 COVID-19 疫苗（包括 KTRs）后密切监测原发性 MN 患者的必要性。如果疫苗接种后出现蛋白尿，应及时进行移植物活检以明确诊断。