C1q-fixing human leukocyte antigen antibodies are specific for predicting transplant glomerulopathy and late graft failure after kidney transplantation.
BACKGROUND
Human leukocyte antigen (HLA) antibodies, especially those that fix complement, are associated with antibody-mediated rejection and graft failure. The C1q assay on single antigen beads detects a subset of HLA antibodies that can fix complement and precede C4d deposition. The aim of this study was to determine whether C1q-fixing antibodies distinguish de novo donor-specific antibodies (DSA) that are clinically relevant and harmful.


METHODS
We retrospectively studied 31 of 274 kidney transplant recipients who had pretransplant and concurrent biopsy and serum specimens, 13 with C4d-positive and 18 with C4d-negative staining. We measured IgG and C1q DSA pretransplant and at the time of biopsy using single antigen bead assays. We identified 13 recipients who developed de novo DSA by IgG or C1q and examined associations with C4d deposition, transplant glomerulopathy, and graft failure.


RESULTS
Testing for DSA by IgG is more sensitive for C4d deposition (IgG: 100%, 95% confidence interval [CI] 0.60-1; C1q: 75%, 95% CI 0.36-0.96). Testing for DSA by C1q is more specific for transplant glomerulopathy (C1q: 81%, 95% CI 0.57-0.94; IgG: 67%, 95% CI 0.43-0.85) and graft loss (C1q: 79%, 95% CI 0.54-0.93; IgG: 63%, 95% CI 0.39-0.83). Absence of de novo DSA by IgG and C1q has a high negative predictive value for the absence of C4d deposition (IgG: 100%, 95% CI 0.73-1; C1q: 88%, 95% CI 0.62-0.98), transplant glomerulopathy (IgG: 100%, 95% CI 0.73-1; C1q: 100%, 95% CI 0.77-1), and graft failure (IgG: 86%, 95% CI 0.56-0.97; C1q: 88%, 95% CI 0.62-0.98).


CONCLUSIONS
Monitoring patients with the C1q assay, which detects antibodies that fix complement, offers a minimally invasive means of identifying patients at risk for transplant glomerulopathy and graft loss.
Division of Nephrology, Department of Medicine, Stanford University, Palo Alto, CA 90095-7430, USA.
Julie M
JM
Yabu
John P
JP
Higgins
Ge
G
Chen
Flavia
F
Sequeira
Stephan
S
Busque
Dolly B
DB
Tyan
D000328:Adult; D000906:Antibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D015922:Complement C1q / Q000276:immunology*; D015935:Complement C4b / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood / Q000453:epidemiology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000453:epidemiology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D010865:Pilot Projects; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity
D000906:Antibodies; D015415:Biomarkers; D006680:HLA Antigens; D010446:Peptide Fragments; D015922:Complement C1q; D015935:Complement C4b; C032261:complement C4d