C4d and non-invasive biomarkers of transplant rejection

Antibody-mediated rejection (ABMR) is the major cause of renal graft dysfunction and loss (1). Currently, renal biopsy remains the gold standard for diagnosing rejection (2). C4d staining in kidney biopsies is widely used to identify the presence of complement activation in the small blood vessels and its deposition is a strong indicator of ABMR (3). In a new study, researchers have used our C4d antibody to identify ABMR and to investigate the diagnostic capacity of non-invasive biomarkers for detecting ABMR in kidney transplant recipients (2).

Kidney Transplant Recipients with Acute Antibody-Mediated Rejection Show Altered Levels of Matrix Metalloproteinases and Their Inhibitors: Evaluation of Circulating MMP and TIMP Profiles. Vázquez-Toledo MA et al., Int J Mol Sci. 2025.

Abstract

Antibody-mediated rejection (ABMR) remains a major cause of renal graft dysfunction and loss. The histological hallmark of antibody-mediated rejection is progressive tissue damage, in which extracellular matrix turnover plays an important role. This turnover is mainly regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Recent studies suggest that MMP/TIMP imbalance may favor the progression of renal damage, inflammation, and fibrosis, but the utility of these molecules as a biomarker of antibody-mediated turnover has not been fully explored. We measured plasma MMP and TIMP levels by ELISA in 15 patients with antibody-mediated renal transplant rejection and 12 patients without rejection. There was a significant increase in MMP-1, MMP-2, and MMP-3 concentrations in the plasma of patients with rejection, directly correlating with the severity of different renal lesions. In contrast, TIMP-3 levels were elevated in patients without rejection, showing a negative correlation with the severity of histopathological lesions. The concentrations of these molecules demonstrated good diagnostic capacity for patients with rejection. Our results show that MMP-1, MMP-2, MMP-3, and TIMP-3 could be potential biomarkers of rejection.

> C4d antibodies by BIOMEDICA – for the identification of human complement split product C4d in paraffin and frozen sections as well as by flow cytometry. 

 

 

Anti-C4dAntibody | BI-RC4D

• widely cited in over 100 publications 

• for immunohistochemistry on paraffin embedded tissue and frozen sections 

• use in kidney, heart, liver and other transplants 

 

Anti-C4d Antibody (FITC) | BI-RC4D-FITC 

• protocol for cell- or solid-phase bound C4 and C4d split product by flow cytometry 

• for kidney, heart, liver and other transplants 

 

Literature:

1. Antibody-mediated rejection of renal allografts: diagnostic pitfalls and challenges. Novotný M, Kment M, Viklický O. Physiol Res. 2021 Dec 30;70(Suppl4):S551-S565. doi: 10.33549/physiolres.934801. PMID: 35199543; PMCID: PMC9054191.
2. Kidney Transplant Recipients with Acute Antibody-Mediated Rejection Show Altered Levels of Matrix Metalloproteinases and Their Inhibitors: Evaluation of Circulating MMP and TIMP Profiles. Vázquez-Toledo MA, Sánchez-Muñoz F, Zepeda-Quiroz I, Guzmán-Martín CA, Osorio-Alonso H, Daniel JV, Soto-Abraham MV, Moguel-González B, Chacón-Salinas R, Flores-Gama C, Springall R.Int J Mol Sci. 2025 Jun 23;26(13):6011. doi: 10.3390/ijms26136011. PMID: 40649789; PMCID: PMC12250063.
3. The importance of C4d in biopsies of kidney transplant recipients. Corrêa RR, Machado JR, da Silva MV, Helmo FR, Guimarães CS, Rocha LP, Faleiros AC, dos Reis MA. Clin Dev Immunol. 2013;2013:678180. doi: 10.1155/2013/678180. Epub 2013 Jul 9. PMID: 23935649; PMCID: PMC3722852.