A systematic review of the role of C4d in the diagnosis of acute antibody-mediated rejection.
In this study, we conducted a systematic review of the literature to re-evaluate the role of C4d in the diagnosis of acute antibody-mediated rejection of kidney allografts. Electronic databases were searched until September 2013. Eligible studies allowed derivation of diagnostic tables for the performance of C4d by immunofluorescence or immunohistochemistry with comparison to histopathological features of acute antibody-mediated rejection and/or donor-specific antibody (DSA) assays. Of 3492 unique abstracts, 29 studies encompassing 3485 indication and 868 surveillance biopsies were identified. Assessment of C4d by immunofluorescence and immunohistochemistry exhibited slight to moderate agreement with glomerulitis, peritubular capillaritis, solid-phase DSA assays, DSA with glomerulitis, and DSA with peritubular capillaritis. The sensitivity and specificity of C4d varied as a function of C4d and comparator test thresholds. Prognostically, the presence of C4d was associated with inferior allograft survival compared with DSA or histopathology alone. Thus, our findings support the presence of complement-dependent and -independent phenotypes of acute antibody-mediated rejection. Whether the presence of C4d in combination with histopathology or DSA should be considered for the diagnosis of acute antibody-mediated rejection warrants further study.
1] Division of Nephrology and the Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada [2] Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada [3] Division of Nephrology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Ruth
R
Sapir-Pichhadze
Division of Nephrology and the Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
Simon P
SP
Curran
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Rohan
R
John
Li Ka Shing Knowledge Institute of St Michael's Hospital, Toronto, Ontario, Canada.
Andrea C
AC
Tricco
The Hospital for Sick Children, Toronto, Ontario, Canada.
Elizabeth
E
Uleryk
1] Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada [2] Li Ka Shing Knowledge Institute of St Michael's Hospital, Toronto, Ontario, Canada.
Andreas
A
Laupacis
1] Division of Nephrology and the Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Kathryn
K
Tinckam
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.
Banu
B
Sis
1] Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada [2] Population Health Sciences, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada [3] Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
Joseph
J
Beyene
1] Division of Nephrology and the Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada [2] Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada [3] Division of Nephrology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Alexander G
AG
Logan
1] Division of Nephrology and the Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada [2] Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada [3] Division of Nephrology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada [4] Division of Nephrology and the Renal Transplant Program, St Michael's Hospital, Toronto, Ontario, Canada.
S Joseph
SJ
Kim
D000208:Acute Disease; D000906:Antibodies / Q000276:immunology*; D015935:Complement C4b / Q000032:analysis*; D005455:Fluorescent Antibody Technique; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D016030:Kidney Transplantation; D010446:Peptide Fragments / Q000032:analysis*; D011379:Prognosis
D000906:Antibodies; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d