Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Aug:112:240-246.
doi: 10.1016/j.molimm.2019.06.002. Epub 2019 Jun 10.

The role of complement in antibody mediated transplant rejection

Joshua M Thurman  1 , Sarah E Panzer  2 , Moglie Le Quintrec  3
Affiliations
Review

The role of complement in antibody mediated transplant rejection

Joshua M Thurman et al. Mol Immunol. 2019 Aug.

Abstract

Antibody mediated transplant rejection (AMR) is a major cause of long-term allograft failure, and currently available treatments are of limited efficacy for treating the disease. AMR is caused by donor specific antibodies (DSA) that bind to antigens within the transplanted organ. DSA usually activate the classical pathway of complement within the allograft, and complement activation is believed to be an important cause of tissue injury in AMR. Several new clinical assays may improve our ability to identify patients at risk of AMR. Complement inhibitory drugs have also been tested in selected patients and in small series. Better understanding of the role of complement activation in the pathogenesis of AMR will likely improve our ability to diagnose the disease and to develop novel treatments.

Keywords: Antibody mediated rejection; Complement; Immunoglobulin; Transplant.

PubMed Disclaimer

Conflict of interest statement

Declaration of interest

JMT receives royalties from Alexion Pharmaceuticals, Inc. JMT is also a consultant for AdMIRx, Inc., a company developing complement inhibitors. He holds stocks and will receive royalty income from AdMIRx.

Figures

Figure 1.
Figure 1.. Antibody mediated complement activation.
Multiple different elements influence complement activation on a target surface. 1) Antigen density will affect the clustering of bound IgG and IgM. Mobility of the antigen on the target surface may also affect clustering of the bound immunoglobulin. 2) IgG and IgM can activate the classical pathway. Some subclasses of IgG are better activators than others. In general IgG3 > IgG1 > IgG2 >> IgG4. C1q binds efficiently to six clustered IgG molecules or to a single IgM that is complexed to antigen. 3) Complement regulatory proteins on the target surface and in plasma control complement pathway activation by the immune complexes. Alternative pathway regulators, such as factor H, decrease amplification through the alternative pathway.
Figure 2.
Figure 2.. Histologic findings in antibody mediated rejection.
A) By light microscopy the peritubular capillaries are congested with leukocytes (“capillaritis”, small arrows). The adjacent tubules are intact and there is little infiltration of the tubules by leukocytes. B) Immunohistochemistry for C4d. C4d staining (brown) can be seen throughout the peritubular capillaries (small arrows) and within the glomerular capillaries (arrowhead).
See this image and copyright information in PMC

References

    1. Alexander JJ, Pickering MC, Haas M, Osawe I, Quigg RJ, 2005. Complement factor h limits immune complex deposition and prevents inflammation and scarring in glomeruli of mice with chronic serum sickness. J Am Soc Nephrol 16, 52–57. - PubMed
    1. Baldwin WM 3rd, Valujskikh A, Fairchild RL, 2015. Mechanisms of antibody-mediated acute and chronic rejection of kidney allografts. Current opinion in organ transplantation. - PMC - PubMed
    1. Bohmig GA, Wahrmann M, Regele H, Exner M, Robl B, Derfler K, Soliman T, Bauer P, Mullner M, Druml W, 2007. Immunoadsorption in severe C4d-positive acute kidney allograft rejection: a randomized controlled trial. Am J Transplant 7, 117–121. - PubMed
    1. Brunn GJ, Saadi S, Platt JL, 2006. Differential regulation of endothelial cell activation by complement and interleukin 1alpha. Circ Res 98, 793–800. - PMC - PubMed
    1. Burbach M, Suberbielle C, Brocheriou I, Ridel C, Mesnard L, Dahan K, Rondeau E, Hertig A, 2014. Report of the inefficacy of eculizumab in two cases of severe antibody-mediated rejection of renal grafts. Transplantation 98, 1056–1059. - PubMed

Publication types

MeSH terms