title: Donor-specific HLA antibodies: evaluating the risk for graft loss in renal transplant recipients with isotype switch from complement fixing IgG1/IgG3 to noncomplement fixing IgG2/IgG4 anti-HLA alloantibodies.
abstract: Human leukocyte antigen alloantibodies have a multitude of damaging effects on the allograft, both complement (C') activation and Fc-independent ones. To date, the clinical significance of non-C' fixing (NCF) HLA donor-specific antibodies (DSA) is still unclear. In this study, we investigated whether renal transplant recipients with NCF-DSA subclasses (IgG2/IgG4, IgA1/IgA2) are at higher risk of graft loss compared to patients with exclusively C' fixing (IgG1/IgG3). Blood samples from 274 patients were analyzed for HLA IgG and IgA subclasses using a modified single-antigen bead assay. We identified 50 (18.2%) patients with circulating NCF antibodies either DSA (n=17) or against third-party HLA (n=33). NCF-DSAs were preferentially of IgG2/IgG4 isotype (11/17) and were mainly directed against HLA class II (13/17). NCF DSA were present as a mixture with strong C' fixing IgG1/IgG3. Graft survival was similar between patients with exclusively C' fixing antibodies and those with a mixture panel (log rang test P=0.162), and also among patients with different immunoglobulin isotype and subclasses (long-rank test, P=0.732). We conclude that expansion of DSA to NCF subclasses postrenal transplantation does not seem to be associated with worse graft survival as compared to the presence of exclusive C' fixing subclasses.
authors.affiliation: Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Arnold
authors.forename: Irma-Sofia
authors.initials: IS
authors.lastname: Ntokou
authors.forename: Ilias I N
authors.initials: II
authors.lastname: Doxiadis
authors.forename: Bernd M
authors.initials: BM
authors.lastname: Spriewald
authors.forename: John N
authors.initials: JN
authors.lastname: Boletis
authors.forename: Aliki G
authors.initials: AG
authors.lastname: Iniotaki
mesh_terms: D000328:Adult; D000918:Antibody Specificity; D003167:Complement Activation; D005260:Female; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D007518:Isoantibodies / Q000097:blood* / Q000145:classification; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D014019:Tissue Donors; D014181:Transplantation Immunology
chemical_list: D006680:HLA Antigens; D007074:Immunoglobulin G; D007518:Isoantibodies
keywords: Anti-HLA antibodies; IgG2/4 alloantibodies; Noncomplement fixing antibodies; class II antibodies; renal transplantation