Pros and cons for C4d as a biomarker.
The introduction of C4d in daily clinical practice in the late nineties aroused an ever-increasing interest in the role of antibody-mediated mechanisms in allograft rejection. As a marker of classical complement activation, C4d made it possible to visualize the direct link between anti-donor antibodies and tissue injury at sites of antibody binding in a graft. With the expanding use of C4d worldwide several limitations of C4d were identified. For instance, in ABO-incompatible transplantations C4d is present in the majority of grafts but this seems to point at 'graft accommodation' rather than antibody-mediated rejection. C4d is now increasingly recognized as a potential biomarker in other fields where antibodies can cause tissue damage, such as systemic autoimmune diseases and pregnancy. In all these fields, C4d holds promise to detect patients at risk for the consequences of antibody-mediated disease. Moreover, the emergence of new therapeutics that block complement activation makes C4d a marker with potential to identify patients who may possibly benefit from these drugs. This review provides an overview of the past, present, and future perspectives of C4d as a biomarker, focusing on its use in solid organ transplantation and discussing its possible new roles in autoimmunity and pregnancy.
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. d.cohen@lumc.nl
Danielle
D
Cohen
Robert B
RB
Colvin
Mohamed R
MR
Daha
Cinthia B
CB
Drachenberg
Mark
M
Haas
Volker
V
Nickeleit
Jane E
JE
Salmon
Banu
B
Sis
Ming-Hui
MH
Zhao
Jan A
JA
Bruijn
Ingeborg M
IM
Bajema
D000022:Abortion, Spontaneous / Q000276:immunology; D015551:Autoimmunity; D015415:Biomarkers / Q000378:metabolism; D015935:Complement C4b / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology / Q000628:therapy; D016027:Heart Transplantation / Q000276:immunology; D006801:Humans; D007674:Kidney Diseases / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology; D016031:Liver Transplantation / Q000276:immunology; D016040:Lung Transplantation / Q000276:immunology; D008297:Male; D018448:Models, Immunological; D016035:Pancreas Transplantation / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy / Q000276:immunology; D014184:Transplantation, Homologous
D015415:Biomarkers; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d