C4d and graft loss in KTR with IgAN

C4d and graft loss in KTR with IgAN (abbrev. KTR: kidney transplant recipients, IgAN: IgA nephropathy)

C4d analysis has become an important diagnostic tool used in the evaluation of kidney transplant recipients (1). C4d is a fragment of the complement component C4 that is produced during the activation of the complement system. In the context of kidney transplantation, the presence of C4d in peritubular capillaries can indicate antibody-mediated injury and help assess the immune status of the transplanted kidney (2).

Our Anti-C4d Antibody (FITC)  has recently been used in a study evaluating whether recurrent IgA deposition, which is common after kidney transplantation, is associated with an increased risk of graft failure (1).

IgA nephropathy (IgAN) is the most prevalent type of kidney disorder. It can occur at any age but is more frequently diagnosed in young adults and adolescents (3). IgAN is marked by the deposition of immunoglobulin A (IgA) in the glomeruli, the filtering units of the kidney. The deposition of IgA, particularly in the mesangial cells of the glomeruli, leads to inflammation and kidney damage (4). The exact cause of IgAN is not fully understood, but it is believed to involve abnormal IgA production and a dysregulation of the immune system. IgA nephropathy (IgAN) has been shown to be associated with a risk for posttransplant recurrence (5, 6).

 C4d and graft loss in KTR with IgAN

The study involved sixty-seven kidney transplant recipients (KTR) of which 37% had recurrent IgA deposition (1). The results showed that “there were no clinical differences between KTR with and without recurrent IgA deposition. C4d was present in 48% of the biopsies. During a median follow-up of 9.6 [4.8-14] years, 18 (27%) KTR developed death-censored graft failure. Recurrent IgA deposition was not associated with graft failure. Of the evaluated complement factors, only C4d staining was associated with graft failure in KTR with recurrent IgA deposition” .  

The authors concluded that “ recurrent IgA deposition was not associated with graft failure in itself. C4d, when present, is strongly associated with graft loss in KTR with recurrent IgA deposition, suggesting a pathogenic role for the lectin pathway in recurrent IgAN.” (1).

Our C4d antibodies are used to identify the human complement split product C4d in paraffin and frozen sections as well as by flow cytometry.

 Anti-C4d Antibody | BI-RC4D

• widely cited in 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

• detection of cell- or solid-phase bound C4d and C4d split product by flow cytometry using FlowPRA® Class I and II screening test beads from One Lambda.

 

Literature

1. C4d, rather than C3d and C5b-9, is associated with graft loss in recurrent IgA deposition after kidney transplantation. Alkaff FF, Uffing A, Tiller G, Lammerts RGM, van den Heuvel MC, Bajema IM, Daha MR, van den Born J, Berger SP. Am J Nephrol. 2024 Aug 17. doi: 10.1159/000540986. Epub ahead of print. PMID: 39154645.
2. The diagnostic significance of C4d deposits, as an immunohistochemical proof of complement activation, in kidney glomerular pathologies and kidney transplantation. Hresko S, Madarova M, Dobosova M, Palusekova N, Niznerova P, Ziaran S, Varga I. Bratisl Lek Listy. 2024;125(5):275-280. doi: 10.4149/BLL_2024_41. PMID: 38624051.
3. Significance of C4d expression in peritubular capillaries concurrent with microvascular inflammation in for-cause biopsies of ABO-incompatible renal allografts. Cho H, Baek CH, Park SK, Kim H, Go H. Kidney Res Clin Pract. 2024 Jan;43(1):82-92. doi: 10.23876/j.krcp.22.221. Epub 2023 May 12. PMID: 37448281; PMCID: PMC10846988.
4. Complement Activation Is Associated With Crescents in IgA Nephropathy. Wang Z, Xie X, Li J, Zhang X, He J, Wang M, Lv J, Zhang H. Front Immunol. 2021 Sep 14;12:676919. doi: 10.3389/fimmu.2021.676919. PMID: 34594322; PMCID: PMC8477028.
5. Risk for graft loss in pediatric and young adult kidney transplant recipients due to recurrent IgA nephropathy. Engen RM, Bartosh SM, Smith JM, Perkins JD, Harshman LA.Am J Transplant. 2024 Jan;24(1):37-45. doi: 10.1016/j.ajt.2023.08.007. Epub 2023 Aug 16. PMID: 37595842.
6. Recurrence of IgA Nephropathy after Kidney Transplantation in Adults. Uffing A, Pérez-Saéz MJ, Jouve Tet al.,. Clin J Am Soc Nephrol. 2021 Aug;16(8):1247-1255. doi: 10.2215/CJN.00910121. PMID: 34362788; PMCID: PMC8455056.