Natural antibody and complement activation characterize patients with idiopathic nephrotic syndrome

Howard Trachtman, Jennifer Laskowski, Cameron Lee, Brandon Renner, Andrew Feemster, Samir Parikh, Sarah E. Panzer, Weixiong Zhong, Paolo Cravedi, Chiara Cantarelli, Liudmila Kulik, Zhiying You, Simon Satchell, Brad Rovin, Fei Liu, Susan L. Kalled, V. Michael Holers, Diana Jalal, Joshua M. Thurman

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are common forms of idiopathic nephrotic syndrome. The causes of these diseases are incompletely understood, but the response of patients to immunosuppressive therapies suggests that their pathogenesis is at least in part immune mediated. Preclinical and clinical research indicates that activation of the classical pathway of complement contributes to glomerular injury in FSGS. Glomerular IgM deposits are also prominent in some patients, raising the possibility that IgM is a trigger of classical pathway activation. In the present study, we examined the pattern of complement activation in the glomeruli and plasma of patients with nephrotic syndrome. We also tested whether patients with FSGS and MCD have elevated levels of natural IgM reactive with epitopes on glomerular endothelial cells and cardiolipin. We found evidence of classical pathway activation in patients with idiopathic nephrotic syndrome compared with healthy control subjects. We also detected higher levels of self-reactive IgM to both targets. Based on these results, IgM and classical pathway activation may contribute to disease pathogenesis in some patients with FSGS and MCD.

Original languageEnglish
Pages (from-to)F505-F516
JournalAmerican Journal of Physiology - Renal Physiology
Issue number4
StatePublished - Oct 2021


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