title: C1q-binding anti-HLA antibodies do not predict platelet transfusion failure in Trial to Reduce Alloimmunization to Platelets study participants.
abstract: In the Trial to Reduce Alloimmunization to Platelets (TRAP) study, 101 of 530 subjects became clinically refractory (CR) to platelets (PLTs) without lymphocytotoxicity assay (LCA)-detectable anti-HLA antibodies. The LCA only detects complement-binding antibodies and is less sensitive than newer assays. Utilizing a more sensitive bead-based assay that does not distinguish between complement-binding versus non-complement-binding antibodies, we have previously shown that while many LCA-negative (LCA-) patients do have anti-HLA antibodies, these low- to moderate-level antibodies do not predict refractoriness. As complement can contribute to PLT rejection, we assessed if previously undetected complement-binding antibodies account for refractoriness among LCA- patients.
  
  
  
  Samples from 169 LCA- (69 CR, 100 non-CR) and 20 LCA-positive (LCA+; 10 CR, 10 non-CR) subjects were selected from the TRAP study serum repository. Anti-Class I HLA immunoglobulin (Ig)G and C1q-binding antibodies were measured in serum or plasma with bead-based detection assays. Levels of C1q-binding antibodies were compared between CR and non-CR subjects and correlated with corrected count increments (CCIs).
  
  
  
  While some of the LCA- subjects had detectable C1q-binding anti-Class I HLA antibodies, and some LCA+ subjects did not, levels were significantly higher among LCA+ subjects. C1q-binding anti-Class I HLA antibody levels did not differ significantly between CR and non-CR among either the LCA- or the LCA+ subjects. Furthermore, there was no significant correlation observed between CCIs and either C1q-binding or any anti-HLA IgG antibodies.
  
  
  
  This work confirms that low- to moderate-level anti-Class I antibodies do not drive PLT rejection, suggesting a role for antibody-independent mechanisms.
authors.affiliation: Blood Systems Research Institute, San Francisco, California.
authors.forename: Rachael P
authors.initials: RP
authors.lastname: Jackman
authors.affiliation: Thermo Fisher Scientific, Canoga Park, California.
authors.forename: Jar-How
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Thermo Fisher Scientific, Canoga Park, California.
authors.forename: Rui
authors.initials: R
authors.lastname: Pei
authors.affiliation: Bloodworks Northwest (formerly Puget Sound Blood Center).
authors.forename: Douglas
authors.initials: D
authors.lastname: Bolgiano
authors.affiliation: Blood Systems Research Institute, San Francisco, California.
authors.forename: Mila
authors.initials: M
authors.lastname: Lebedeva
authors.affiliation: Bloodworks Northwest (formerly Puget Sound Blood Center).|University of Washington School of Medicine, Seattle, Washington.
authors.forename: Sherrill J
authors.initials: SJ
authors.lastname: Slichter
authors.affiliation: Blood Systems Research Institute, San Francisco, California.|University of California, San Francisco, California.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Norris
mesh_terms: D001792:Blood Platelets / Q000276:immunology; D015922:Complement C1q / Q000378:metabolism*; D006680:HLA Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000276:immunology* / Q000378:metabolism; D017713:Platelet Transfusion / Q000009:adverse effects*; D011237:Predictive Value of Tests; D011485:Protein Binding
chemical_list: D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D007518:Isoantibodies; D015922:Complement C1q