Urine IgG4 May Be a Specific Biomarker to Monitor the Progression of Phospholipase A2 Receptor (PLA2R)-Positive Primary Membranous Glomerulopathy (pMGN)
Document Type
Conference Proceeding
Publication Date
10-2024
Publication Title
Journal of the American Society of Nephrology
Abstract
Introduction: PLA2R is known to be closely related to IgG4 in the serum of patients with pMGN. Our recent study indicated that PLA2R staining in the glomeruli of renal biopsies remained positive in different stages of pMGN (usually graded as stage 1 to 4, subepithelial to resolving deposits by electron microscopy [EM]). IgG4 staining was positive in stage 1-2 p-MGN. In contrast, its staining faded away in glomerular basement membranes (GBM) due to its low affinity to GBM in stage 3-4 pMGN. This pilot study was to determine if urine IgG4 was reduced in stage 3- 4 pMGN when compared to stage 1-2 pMGN. Case Description: Patient #1 had nephrotic range proteinuria. His transplant renal biopsy showed De Novo pMGN with positive stains for both PLA2R and IgG4, and stage 1 subepithelial deposits by EM. Patient #2 also had nephrotic range proteinuria and his transplant renal biopsy showed recurrent pMGN with positive PLA2R but focal/weak IgG4 staining. The EM for patient #2 showed stage 3-4 intramembranous vacuoles. Urine IgG4 levels were measured in both transplant patients with pMGN. Relative urine IgG4 concentrations were comapred against measurements from normal urine ( < 0.03 mg/dl, negative control) and a positive control (peak IgG4 of 6.64 mg/dl). Patient #1 had a urine IgG4 level at 3.13 mg/dl and urine protein/creatinine ratio (UPCR) at 7.55 mg/mg, thus producing 0.415 mg/dl IgG4 per unit urine protein by dividing two indices (see Table below). Similarly, patient #2 had urine IgG4 level at 2.10 mg/dl and UPCR at 4.96 mg/mg, thus generating 0.423 mg/dl IgG4 per unit urine protein by dividing two indices. There was no significant difference in urine IgG4 levels between them. Discussion: Our pilot study suggests that IgG4 immuno-staining may only reflect stages of immune complex deposits seen by EM but cannot correlate with the urine level of IgG4. However the urine IgG4 measurement may serve as a non-invasive biomarker to monitor progression of pMGN. Additional studies are required to further validate this claim.
Volume
35
Issue
10S
First Page
1306
Recommended Citation
Zhang PL, Maine GN, Young D, Singh A, Samarapungavan D. Urine IgG4 may be a specific biomarker to monitor the progression of phospholipase A2 receptor (PLA2R)-positive primary membranous glomerulopathy (pMGN). J Am Soc Nephrol. 2024 Oct;35(10S):1306. doi:10.1681/ASN.2024ankxhd9a
DOI
10.1681/ASN.2024ankxhd9a
Comments
Kidney Week, American Society of Nephrology, October 24-27, 2024, San Diego, CA