在膜性狼疮肾炎患者中，外生骨疣阳性和外生骨疣阴性代表两种不同的表型。
In Patients with Membranous Lupus Nephritis, Exostosin-Positivity and Exostosin-Negativity Represent Two Different Phenotypes.
机构信息
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota.
出版信息
J Am Soc Nephrol. 2021 Mar;32(3):695-706. doi: 10.1681/ASN.2020081181. Epub 2021 Jan 21.
BACKGROUND
In patients with secondary (autoimmune) membranous nephropathy, two novel proteins, Exostosin 1 and Exostosin 2 (EXT1/EXT2), are potential disease antigens, biomarkers, or both. In this study, we validate the EXT1/EXT2 findings in a large cohort of membranous lupus nephritis.
METHODS
We conducted a retrospective cohort study of patients with membranous lupus nephritis, and performed immunohistochemistry studies on the kidney biopsy specimens against EXT1 and EXT2. Clinicopathologic features and outcomes of EXT1/EXT2-positive versus EXT1/EXT2-negative patients were compared.
RESULTS
Our study cohort included 374 biopsy-proven membranous lupus nephritis cases, of which 122 (32.6%) were EXT1/EXT2-positive and 252 (67.4%) were EXT1/EXT2-negative. EXT1/EXT2-positive patients were significantly younger (=0.01), had significantly lower serum creatinine levels (=0.02), were significantly more likely to present with proteinuria ≥3.5 g/24 h (=0.009), and had significantly less chronicity features (glomerulosclerosis, =0.001 or interstitial fibrosis and tubular atrophy, <0.001) on kidney biopsy. Clinical follow-up data were available for 160 patients, of which 64 (40%) biopsy results were EXT1/EXT2-positive and 96 (60%) were EXT1/EXT2-negative. The proportion of patients with class 3/4 lupus nephritis coexisting with membranous lupus nephritis was not different between the EXT1/EXT2-positive and EXT1/EXT2-negative groups (25.0% versus 32.3%; 0.32). The patients who were EXT1/EXT2-negative evolved to ESKD faster and more frequently compared with EXT1/EXT2-positive patients (18.8% versus 3.1%; =0.003).
CONCLUSIONS
The prevalence of EXT1/EXT2 positivity was 32.6% in our cohort of membranous lupus nephritis. Compared with EXT1/EXT2-negative membranous lupus nephritis, EXT1/EXT2-positive disease appears to represent a subgroup with favorable kidney biopsy findings with respect to chronicity indices. Cases of membranous lupus nephritis that are EXT1/EXT2-negative are more likely to progress to ESKD compared with those that are EXT1/EXT2-positive.
背景
在继发性（自身免疫性）膜性肾病患者中，两种新型蛋白 Exostosin 1 和 Exostosin 2（EXT1/EXT2）可能是疾病的抗原、生物标志物或兼而有之。在这项研究中，我们在一个大型膜性狼疮肾炎队列中验证了 EXT1/EXT2 的发现。
方法
我们进行了一项回顾性队列研究，纳入了膜性狼疮肾炎患者，并对肾活检标本进行 EXT1 和 EXT2 的免疫组织化学研究。比较了 EXT1/EXT2 阳性与 EXT1/EXT2 阴性患者的临床病理特征和结局。
结果
我们的研究队列包括 374 例经活检证实的膜性狼疮肾炎病例，其中 122 例（32.6%）为 EXT1/EXT2 阳性，252 例（67.4%）为 EXT1/EXT2 阴性。EXT1/EXT2 阳性患者明显更年轻（=0.01），血清肌酐水平明显更低（=0.02），蛋白尿≥3.5 g/24 h 的可能性明显更高（=0.009），且肾活检中肾小球硬化（=0.001）或间质纤维化和肾小管萎缩（<0.001）的慢性特征明显更少。160 例患者有临床随访数据，其中 64 例（40%）的活检结果为 EXT1/EXT2 阳性，96 例（60%）为 EXT1/EXT2 阴性。伴有膜性狼疮肾炎的 3/4 级狼疮肾炎患者的比例在 EXT1/EXT2 阳性和 EXT1/EXT2 阴性组之间无差异（25.0%比 32.3%；0.32）。与 EXT1/EXT2 阳性患者相比，EXT1/EXT2 阴性患者更快、更频繁地进展为终末期肾病（18.8%比 3.1%；=0.003）。
结论
在我们的膜性狼疮肾炎队列中，EXT1/EXT2 阳性率为 32.6%。与 EXT1/EXT2 阴性的膜性狼疮肾炎相比，EXT1/EXT2 阳性疾病似乎代表了一个亚组，其在慢性指数方面具有更好的肾脏活检表现。与 EXT1/EXT2 阳性的膜性狼疮肾炎相比，EXT1/EXT2 阴性的膜性狼疮肾炎更有可能进展为终末期肾病。
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