C4d and C3d staining in biopsies of ABO- and HLA-incompatible renal allografts: correlation with histologic findings.
Biopsies of ABO-incompatible and positive crossmatch (HLA-incompatible) renal allografts were retrospectively examined to compare results of C4d and C3d staining, and the correlation between such staining and histologic findings suggestive of antibody-mediated rejection (AMR). A total of 75 biopsies (55 protocol, 17 for graft dysfunction, 3 for other indications) of 24 ABO-incompatible grafts and 244 biopsies (103 protocol, 129 for graft dysfunction, 12 for other indications) of 66 HLA-incompatible grafts were examined; all were stained for C4d and approximately 40% for C3d. In ABO-incompatible grafts, 80% of protocol biopsies and 59% performed for graft dysfunction showed C4d staining in peritubular capillaries (PTC); this staining was not correlated with neutrophil margination in PTC. In HLA-incompatible grafts, PTC C4d was present in 26% of protocol biopsies and 60% of biopsies for graft dysfunction; 92% of biopsies with >1+ (0-4+ scale), diffuse PTC C4d had > or =1+ margination and/or thrombotic microangiopathy (TMA), compared with 12% of C4d-negative biopsies. C3d was somewhat more predictive of margination than C4d in ABO-incompatible, but not HLA-incompatible, grafts. In summary, while PTC C4d deposition indicates probable AMR in biopsies of HLA-incompatible grafts, including protocol biopsies, there is no histologic evidence that C4d deposition is correlated with injury in most ABO-incompatible grafts.
Haas
M
M
Department of Pathology, John Hopkins Medical Institutions, Baltimore, Maryland, USA.
Rahman
M H
MH
Racusen
L C
LC
Kraus
E S
ES
Bagnasco
S M
SM
Segev
D L
DL
Simpkins
C E
CE
Warren
D S
DS
King
K E
KE
Zachary
A A
AA
Montgomery
R A
RA
D000017:ABO Blood-Group System / Q000276:immunology / Q000378:metabolism; D000906:Antibodies / Q000276:immunology; D001706:Biopsy; D001787:Blood Group Incompatibility / Q000276:immunology* / Q000378:metabolism; D015933:Complement C3d / Q000378:metabolism*; D003181:Complement C4 / Q000378:metabolism*; D006084:Graft Rejection / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D007674:Kidney Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology*; D014184:Transplantation, Homologous / Q000276:immunology
D000017:ABO Blood-Group System; D000906:Antibodies; D003181:Complement C4; D006680:HLA Antigens; D015933:Complement C3d