Journal article
Natural antibody and complement activation characterize patients with idiopathic nephrotic syndrome
American journal of physiology. Renal physiology, Vol.321(4), pp.F505-F516
08/30/2021
DOI: 10.1152/ajprenal.00041.2021
PMCID: PMC8560405
PMID: 34459222
Abstract
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.
NEW & NOTEWORTHY
IgM is detected in biopsies from some patients with nephrotic syndrome, although this has been attributed to passive trapping of the protein. We found, however, that IgM colocalizes with complement activation fragments in some glomeruli. We also found that affected patients had higher levels of IgM reactive to glomerular endothelial cell epitopes. Thus, IgM activates the complement system in the glomeruli of some patients with nephrotic syndrome and may contribute to injury.
Details
- Title: Subtitle
- Natural antibody and complement activation characterize patients with idiopathic nephrotic syndrome
- Creators
- Howard Trachtman - NYU Langone HealthJennifer Laskowski - University of Colorado Anschutz Medical CampusCameron Lee - University of Colorado Anschutz Medical CampusBrandon Renner - University of Colorado Anschutz Medical CampusAndrew Feemster - NYU Langone HealthSamir Parikh - The Ohio State University Wexner Medical CenterSarah E. Panzer - UW Health University HospitalWeixiong Zhong - UW Health University HospitalPaolo Cravedi - Icahn School of Medicine at Mount SinaiChiara Cantarelli - University of ParmaLiudmila Kulik - University of Colorado Anschutz Medical CampusZhiying You - University of Colorado Anschutz Medical CampusSimon Satchell - University of BristolBrad Rovin - The Ohio State University Wexner Medical CenterFei LiuSusan L. KalledV. Michael Holers - University of Colorado Anschutz Medical CampusDiana Jalal - University of IowaJoshua M. Thurman - University of Colorado Anschutz Medical Campus
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Renal physiology, Vol.321(4), pp.F505-F516
- DOI
- 10.1152/ajprenal.00041.2021
- PMID
- 34459222
- PMCID
- PMC8560405
- NLM abbreviation
- Am J Physiol Renal Physiol
- ISSN
- 1931-857X
- eISSN
- 1522-1466
- Publisher
- American Physiological Society
- Grant note
- ; LR180050 / ; DK113586 / ; DK076690 / ;
- Alternative title
- IgM AND FSGS
- Language
- English
- Date published
- 08/30/2021
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984359885902771
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