Clinical usefulness of a novel C1q assay to detect immunoglobulin G antibodies capable of fixing complement in sensitized pediatric heart transplant patients.
BACKGROUND
Donor-specific antibodies (DSA) against human leukocyte antigens complicate transplantation with the potential for acute antibody-mediated rejection (AMR). Complement-fixing antibodies are required to initiate the complement cascade. Not all DSAs, however, can fix complement.


METHODS
A novel C1q assay was developed to detect the sub-set of immunoglobulin G (IgG) antibodies capable of fixing complement. Sera from 18 pediatric heart transplant patients were analyzed for DSAs using a Luminex platform (Luminex Inc, Austin, TX) and commercially available single-antigen bead assay kits. Biopsy specimens were assessed for AMR using histopathologic criteria and immunohistochemical staining.


RESULTS
During the study period, 5 patients had AMR; of these, 2 were C1q virtual crossmatch positive (VXM+) and had persistent C1q DSAs after transplant, and 3 were C1q VXM- but antibody developed immediately after transplant. A positive C1q assay in the immediate post-transplant period had a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 100%, with 100% sensitivity and 100% specificity (Fisher exact p = 0.001). Of 11 patients who were IgG VXM+, 5 had AMR; the IgG VXM had a PPV of 45% and NPV of 100%, with 100% sensitivity and 54% specificity (Fisher exact p = 0.101).


CONCLUSIONS
The C1q assay can detect a sub-set of antibodies capable of fixing complement and predicts AMR early after transplant. Avoiding only the donor antigens that would be recognized by the C1q assay may accelerate time to transplant by expansion of the donor pool and potentially allows transplantation of previously "incompatible" organs.
Chin
Clifford
C
Department of Pediatrics, Division of Pediatric Cardiology, Stanford Unversity, Stanford, California, USA. clifford@leland.stanford.edu
Chen
Ge
G
Sequeria
Flavia
F
Berry
Gerald
G
Siehr
Stephanie
S
Bernstein
Daniel
D
Rosenthal
David
D
Reinhartz
Olaf
O
Tyan
Dolly
D
D000293:Adolescent; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D015922:Complement C1q / Q000378:metabolism*; D003168:Complement Fixation Tests / Q000379:methods*; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology*; D006680:HLA Antigens / Q000097:blood; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D006650:Histocompatibility Testing; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007223:Infant; D012189:Retrospective Studies
D006680:HLA Antigens; D007074:Immunoglobulin G; D015922:Complement C1q