title: Efficacy of induction therapy with ATG and intravenous immunoglobulins in patients with low-level donor-specific HLA-antibodies.
abstract: Low-level donor-specific HLA-antibodies (HLA-DSA) (i.e. detectable by single-antigen flow beads, but negative by complement-dependent cytotoxicity crossmatch) represent a risk factor for early allograft rejection. The short-term efficacy of an induction regimen consisting of polyclonal anti-T-lymphocyte globulin (ATG) and intravenous immunoglobulins (IvIg) in patients with low-level HLA-DSA is unknown. In this study, we compared 67 patients with low-level HLA-DSA not having received ATG/IvIg induction (historic control) with 37 patients, who received ATG/IvIg induction. The two groups were equal regarding retransplants, HLA-matches, number and class of HLA-DSA. The overall incidence of clinical/subclinical antibody-mediated rejection (AMR) was lower in the ATG/IvIg than in the historic control group (38% vs. 55%; p = 0.03). This was driven by a significantly lower rate of clinical AMR (11% vs. 46%; p = 0.0002). Clinical T-cell-mediated rejection (TCR) was significantly lower in the ATG/IvIg than in the historic control group (0% vs. 50%; p < 0.0001). Within the first year, allograft loss due to AMR occurred in 7.5% in the historic control and in 0% in the ATG/IvIg group. We conclude that in patients with low-level HLA-DSA, ATG/IvIg induction significantly reduces TCR and the severity of AMR, but the high rate of subclinical AMR suggests an insufficient control of the humoral immune response.
authors.affiliation: Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Bächler
authors.forename: P
authors.initials: P
authors.lastname: Amico
authors.forename: G
authors.initials: G
authors.lastname: Hönger
authors.forename: D
authors.initials: D
authors.lastname: Bielmann
authors.forename: H
authors.initials: H
authors.lastname: Hopfer
authors.forename: M J
authors.initials: MJ
authors.lastname: Mihatsch
authors.forename: J
authors.initials: J
authors.lastname: Steiger
authors.forename: S
authors.initials: S
authors.lastname: Schaub
mesh_terms: D000906:Antibodies / Q000276:immunology*; D002985:Clinical Protocols; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology; D014019:Tissue Donors / Q000706:statistics & numerical data*
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; C025991:Thomsen-Friedenreich antibodies