C4d-fixing capability of low-level donor-specific HLA antibodies is not predictive for early antibody-mediated rejection.
BACKGROUND
Recent studies indicate that not all low-level donor-specific human leukocyte antigen (HLA) antibodies (HLA-DSA) (i.e., positive by solid-phase assays, negative by complement-dependent cytotoxic-crossmatch) have a detrimental clinical impact. The aim of this study was to investigate whether the pretransplant C4d-fixing capability allows distinguishing harmful from presumably clinically irrelevant HLA-DSA.


METHODS
We retrospectively investigated 64 patients with low-level HLA-DSA detected by single-antigen flow beads (SAFB). Thirty-four of 64 patients (53%) experienced early antibody-mediated rejection (AMR), whereas 30 patients (47%) did not. HLA-DSA characteristics (i.e., number, class, and strength), frequency of retransplants, and immunosuppressive regimens were not different in these two groups. Pretransplant sera were reanalyzed using a modified SAFB assay measuring C4d fixation induced by HLA antibodies.


RESULTS
C4d-fixing HLA-DSA were observed in 11 of 64 patients (17%). AMR occurred in 6 of 11 patients (55%) with C4d-fixing HLA-DSA and in 28 of 53 patients (53%) without C4d-fixing HLA-DSA (P=1.0). Positive C4d staining in peritubular capillaries was detected in 6 of 11 patients (55%) with C4d-fixing HLA-DSA and in 21 of 53 patients (40%) without C4d-fixing HLA-DSA (P=0.50).


CONCLUSIONS
The pretransplant capability of low-level HLA-DSA to trigger C4d fixation in vitro is not predictive for early AMR or C4d deposition in peritubular capillaries in vivo. This argues against pretransplant C4d SAFB testing to define the clinical relevance of low-level HLA-DSA.
Hönger
Gideon
G
Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
Wahrmann
Markus
M
Amico
Patrizia
P
Hopfer
Helmut
H
Böhmig
Georg A
GA
Schaub
Stefan
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000737:chemistry*; D001706:Biopsy; D002196:Capillaries / Q000276:immunology; D015935:Complement C4b / Q000737:chemistry; D005260:Female; D006084:Graft Rejection; D006680:HLA Antigens / Q000737:chemistry*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000737:chemistry; D012189:Retrospective Studies
D000906:Antibodies; D006680:HLA Antigens; D007074:Immunoglobulin G; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d