title: Impact of IgG3 subclass and C1q-fixing donor-specific HLA alloantibodies on rejection and survival in liver transplantation.
abstract: Recent literature confirms donor-specific HLA alloantibodies (DSA) impair 5-year survival in some but not all liver transplant recipients. In an effort to improve DSA testing's association with rejection and death, we retrospectively evaluated 1270 liver transplant recipients for the presence of IgG3 and C1q-fixing DSA. In patients with preformed DSA, 29 and 51% had IgG3 and C1q-fixing DSA, respectively. In patients with de novo DSA, 62% and 67% had IgG3 and C1q-fixing DSA, respectively. When different types of DSA positive patients were compared to DSA negative patients, multivariable analysis showed that IgG3 DSA positivity had the highest numerical hazard ratio for death (IgG3: HR = 2.4, p < 0.001; C1q: HR = 1.9, p < 0.001; standard DSA: HR = 1.6, p < 0.001). Similarly, multivariable analysis demonstrated de novo IgG3 DSA positivity compared to no DSA had the highest hazard ratio for death (IgG3: HR = 2.1, p = 0.004; C1q: HR = 1.9, p = 0.02; standard DSA: HR = 1.8, p = 0.007). Preformed C1q-fixing class II DSA showed the strongest correlation with early rejection. In conclusion, preformed and de novo IgG3 subclass DSA positive patients had the highest absolute HR for death in side-by-side comparison with C1q and standard DSA positive versus DSA negative patients; however, IgG3 negative DSA positive patients still had inferior outcomes compared to DSA negative patients.
authors.affiliation: Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX.
authors.forename: J G
authors.initials: JG
authors.lastname: O'Leary
authors.forename: H
authors.initials: H
authors.lastname: Kaneku
authors.forename: N
authors.initials: N
authors.lastname: Banuelos
authors.forename: L W
authors.initials: LW
authors.lastname: Jennings
authors.forename: G B
authors.initials: GB
authors.lastname: Klintmalm
authors.forename: P I
authors.initials: PI
authors.lastname: Terasaki
mesh_terms: D000328:Adult; D015922:Complement C1q / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007518:Isoantibodies / Q000276:immunology*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged
chemical_list: D006680:HLA Antigens; D007074:Immunoglobulin G; D007518:Isoantibodies; D015922:Complement C1q