Department of Pediatric Nephrology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, Netherlands.
Innatoss Laboratories, Oss, Netherlands.
Front Immunol. 2022 Nov 14;13:1036136. doi: 10.3389/fimmu.2022.1036136. eCollection 2022.
Nephritic factors (NeFs) are autoantibodies promoting the activity of the central enzymes of the complement cascade, an important first line of defense of our innate immune system. NeFs stabilize the complement convertase complexes and prevent their natural and regulator-mediated decay. They are mostly associated with rare complement-mediated kidney disorders, in particular with C3 glomerulopathy and related diseases. Although these autoantibodies were already described more than 50 years ago, measuring NeFs for diagnostic purposes remains difficult, and this also complicates our understanding of their clinical associations. In this review, we address the multifactorial challenges of NeF diagnostics. We describe the diseases NeFs are associated with, the heterogenic mechanisms of action of different NeF types, the different methods available in laboratories used for their detection, and efforts for standardization. Finally, we discuss the importance of proper NeF diagnostics for understanding the clinical impact of these autoantibodies in disease pathophysiology and for considering future complement-directed therapy.
肾因子（NeFs）是自身抗体，可促进补体级联反应的中心酶的活性，这是我们固有免疫系统的重要第一道防线。NeFs 稳定补体转化酶复合物并防止其自然和调节剂介导的降解。它们主要与罕见的补体介导的肾脏疾病有关，特别是与 C3 肾小球病和相关疾病有关。尽管这些自身抗体早在 50 多年前就已被描述，但出于诊断目的测量 NeFs 仍然很困难，这也使我们对其临床关联的理解变得复杂。在这篇综述中，我们探讨了 NeF 诊断的多因素挑战。我们描述了 NeFs 相关的疾病、不同 NeF 类型的异质作用机制、实验室用于检测它们的不同方法以及标准化的努力。最后，我们讨论了正确的 NeF 诊断在了解这些自身抗体在疾病发病机制中的临床影响以及考虑未来补体靶向治疗的重要性。
