PMID- 21116220 OWN - NLM STAT- MEDLINE DCOM- 20110307 LR - 20151119 IS - 1534-6080 (Electronic) IS - 0041-1337 (Linking) VI - 91 IP - 3 DP - 2011 Feb 15 TI - C1q-fixing human leukocyte antigen antibodies are specific for predicting transplant glomerulopathy and late graft failure after kidney transplantation. PG - 342-7 LID - 10.1097/TP.0b013e318203fd26 [doi] AB - 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). CONCLUSION: 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. FAU - Yabu, Julie M AU - Yabu JM AD - Division of Nephrology, Department of Medicine, Stanford University, Palo Alto, CA 90095-7430, USA. FAU - Higgins, John P AU - Higgins JP FAU - Chen, Ge AU - Chen G FAU - Sequeira, Flavia AU - Sequeira F FAU - Busque, Stephan AU - Busque S FAU - Tyan, Dolly B AU - Tyan DB LA - eng PT - Journal Article PL - United States TA - Transplantation JT - Transplantation JID - 0132144 RN - 0 (Antibodies) RN - 0 (Biomarkers) RN - 0 (HLA Antigens) RN - 0 (Peptide Fragments) RN - 80295-33-6 (Complement C1q) RN - 80295-50-7 (Complement C4b) RN - 80295-52-9 (complement C4d) SB - IM MH - Adult MH - Antibodies/*blood MH - Biomarkers/blood MH - Biopsy MH - Complement C1q/*immunology MH - Complement C4b/metabolism MH - Female MH - Follow-Up Studies MH - Graft Rejection/blood/*epidemiology MH - HLA Antigens/*immunology MH - Humans MH - Kaplan-Meier Estimate MH - Kidney/metabolism/pathology MH - Kidney Diseases/blood/*epidemiology MH - *Kidney Transplantation MH - Male MH - Middle Aged MH - Peptide Fragments/metabolism MH - Pilot Projects MH - Predictive Value of Tests MH - Retrospective Studies MH - Risk Factors MH - Sensitivity and Specificity EDAT- 2010/12/01 06:00 MHDA- 2011/03/08 06:00 CRDT- 2010/12/01 06:00 PHST- 2010/12/01 06:00 [entrez] PHST- 2010/12/01 06:00 [pubmed] PHST- 2011/03/08 06:00 [medline] AID - 10.1097/TP.0b013e318203fd26 [doi] PST - ppublish SO - Transplantation. 2011 Feb 15;91(3):342-7. doi: 10.1097/TP.0b013e318203fd26.