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Natural antibody and complement activation characterize patients with idiopathic nephrotic syndrome.
- Source :
-
American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2021 Oct 01; Vol. 321 (4), pp. F505-F516. Date of Electronic Publication: 2021 Aug 30. - Publication Year :
- 2021
-
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.
- Subjects :
- Adult
Aged
Antibody Specificity
Case-Control Studies
Endothelial Cells drug effects
Female
Glomerulosclerosis, Focal Segmental blood
Glomerulosclerosis, Focal Segmental drug therapy
Glomerulosclerosis, Focal Segmental pathology
Humans
Immunoglobulin M blood
Immunosuppressive Agents therapeutic use
Kidney Glomerulus drug effects
Kidney Glomerulus pathology
Male
Middle Aged
Nephrosis, Lipoid drug therapy
Nephrosis, Lipoid pathology
Nephrotic Syndrome drug therapy
Nephrotic Syndrome pathology
Treatment Outcome
Young Adult
Cardiolipins immunology
Complement Pathway, Classical drug effects
Complement System Proteins analysis
Endothelial Cells immunology
Epitopes
Glomerulosclerosis, Focal Segmental immunology
Immunoglobulin M analysis
Kidney Glomerulus immunology
Nephrosis, Lipoid immunology
Nephrotic Syndrome immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1466
- Volume :
- 321
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Renal physiology
- Publication Type :
- Academic Journal
- Accession number :
- 34459222
- Full Text :
- https://doi.org/10.1152/ajprenal.00041.2021