title: Pretransplant IgG subclasses of donor-specific human leukocyte antigen antibodies and development of antibody-mediated rejection.
abstract: BACKGROUND
  The subclass of IgG antibodies contributes to their capability to activate complement. It is currently unknown whether the pretransplant IgG subclass composition allows distinguishing harmful from presumably irrelevant donor-specific human leukocyte antigen (HLA) antibodies (HLA-DSA) detected by single-antigen flow beads (SAFB).
  
  
  METHODS
  Seventy-four patients transplanted in the presence of HLA-DSA were investigated. HLA-DSA characteristics were not different between patients experiencing antibody-mediated rejection (AMR) (n=40) and patients who did not (n=34) experience AMR. Sera were reanalyzed using SAFB with IgG subclass-specific reporter antibodies.
  
  
  RESULTS
  The 74 patients had in total 141 HLA-DSA. IgG1 was the predominant subclass (78%), followed by IgG2 (49%), IgG3 (36%), and IgG4 (20%). When grouped according to the complement-activating capability, only 4 of 74 patients (5%) had exclusively weak/no complement-activating HLA-DSA (i.e., IgG2 and IgG4), 21 of 74 patients (28%) had isolated strong complement-activating HLA-DSA (i.e., IgG1 and IgG3), and 46 of 74 patients (62%) had a mixture of both. There was no difference between the strong complement-activating and the mixture group regarding incidence of AMR (57% vs. 54%; P=0.81), phenotypes of AMR (P=0.70), and death-censored allograft survival at 5 years (78% vs. 78%; P=0.74). Interestingly, patients with exclusively weak/no complement-activating HLA-DSA (n=4) had a numerically lower incidence of AMR (25%) and no allograft loss has occurred yet.
  
  
  CONCLUSIONS
  In 90% of patients, pretransplant HLA-DSA are composed of isolated strong or a mixture of strong and weak/no complement-activating IgG subclasses. Because outcomes in these two groups were similar, pretransplant IgG subclass analysis is likely not providing substantial value beyond the standard IgG SAFB assay for pretransplant risk stratification.
authors.affiliation: Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
authors.forename: Gideon
authors.initials: G
authors.lastname: Hönger
authors.forename: Helmut
authors.initials: H
authors.lastname: Hopfer
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Arnold
authors.forename: Bernd M
authors.initials: BM
authors.lastname: Spriewald
authors.forename: Stefan
authors.initials: S
authors.lastname: Schaub
authors.forename: Patrizia
authors.initials: P
authors.lastname: Amico
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003167:Complement Activation; D005260:Female; D006084:Graft Rejection / Q000209:etiology* / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007118:Immunoassay; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification*; D007518:Isoantibodies / Q000097:blood / Q000145:classification*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012307:Risk Factors; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D007074:Immunoglobulin G; D007518:Isoantibodies