Antibody Panel Predicts Risk of Organ Loss Prior to Kidney Transplantation

An ELISA test based on a panel of seven antibodies can help identify primary focal segmental glomerulosclerosis (FSGS) patients at high risk of recurrence before kidney transplantation.

Recurrence of FSGS after kidney transplantation is a cause of accelerated graft loss. Recurrence is managed by immunosuppressive drugs along with current standards of treatment that include salt restriction, diuretics and steroids, plasma filtration, and immunoadsorption.

To identify biomarkers for risk of recurring FSGS prior to kidney transplantation, investigators at the University of California, San Francisco (USA) and Rush University Medical Center (Chicago, IL, USA) processed 141 serum samples from 64 patients with and without primary recurring FSGS and 34 non-FSGS control patients transplanted at four hospitals. They screened about 9,000 antigens in pre-transplant sera and selected 10 antibodies targeting glomerular antigens for enzyme-linked immunosorbent assay (ELISA) validation.

Results revealed that a panel of seven antibodies (CD40, PTPRO, CGB5, FAS, P2RY11, SNRPB2, and APOL2) could predict post-transplant FSGS recurrence with 92% accuracy. Pre-transplant elevation of anti-CD40 antibody alone had the best correlation (78% accuracy) with recurring FSGS risk after transplantation.

The CD40 protein is a member of the TNF-receptor superfamily. This receptor has been found to be essential in mediating a broad variety of immune and inflammatory responses including T-cell-dependent immunoglobulin class switching, memory B- cell development, and germinal center formation. Epitope mapping of CD40 with customized peptide arrays and recurring FSGS sera demonstrated altered immunogenicity of the extracellular CD40 domain in recurring FSGS patients. Immunohistochemistry of CD40 demonstrated a differential expression in FSGS compared to non-FSGS controls.

“This is a new blood test to monitor patients before kidney transplant and predict who may have recurrence of FSGS, thereby preventing loss of kidneys,” said senior author Dr. Minnie M. Sarwal, professor of transplant surgery at the University of California, San Francisco. “We want to predict FSGS recurrence before we put a kidney in. We then can treat the high-risk patients with a new drug to possibly prevent disease.”

Related Links:
University of California, San Francisco
Rush University Medical Center