Transforming Growth Factor Beta Receptor 3 (TGFBR3)-Associated Membranous Nephropathy.

Area of Science:

• Nephrology
• Immunology
• Pathology

Background:

• Membranous lupus nephritis (MLN) accounts for 10%-15% of lupus nephritis cases.
• MLN increases patient morbidity and mortality due to nephrotic syndrome and chronic kidney failure.
• Identifying MLN target antigens could enable noninvasive monitoring, guide treatment, and aid prognostication.

Purpose of the Study:

• To identify novel biomarkers for membranous lupus nephritis (MLN).
• To investigate the role of type III TGF-β receptor (TGFBR3) as a potential biomarker in MLN.

Main Methods:

• Protein discovery using mass spectrometry on glomerular proteins and eluted immune complexes from MLN biopsies.
• Confocal microscopy to evaluate colocalization of proteins with IgG in glomerular immune deposits.
• Immunostaining of consecutive cases to determine TGFBR3 prevalence in membranous nephropathy (MN) and MLN.

Main Results:

• TGFBR3 was enriched in glomeruli and co-precipitated with IgG in a subset of MLN biopsies.
• TGFBR3 was not found in MN cases without SLE (0/104), but present in 6% of MLN cases (11/199).
• TGFBR3 colocalized with IgG in glomerular immune deposits in TGFBR3-associated MN.

Conclusions:

• Positive TGFBR3 staining in glomerular immune deposits indicates a distinct form of MN, enriched in MLN.
• Diagnosing TGFBR3-associated MN prompts clinicians to investigate for underlying autoimmune diseases like SLE.