C1q-binding anti-HLA antibodies do not predict platelet transfusion failure in Trial to Reduce Alloimmunization to Platelets study participants.
Pubmed ID: 27079754
Pubmed Central ID: PMC6016838
Publication Date: 06/01/2016
Affiliation: University of California, San Francisco, California.
MeSH Terms: Humans, Predictive Value of Tests, Platelet Transfusion, HLA Antigens, Blood Platelets, Protein Binding, Histocompatibility Antigens Class I, Complement C1q, Isoantibodies
Grants: R01 HL095470, R21 HL124260
Authors: Lee JH, Jackman RP, Bolgiano D, Lebedeva M, Slichter SJ, Norris PJ, Pei R
Cite As: Jackman RP, Lee JH, Pei R, Bolgiano D, Lebedeva M, Slichter SJ, Norris PJ. C1q-binding anti-HLA antibodies do not predict platelet transfusion failure in Trial to Reduce Alloimmunization to Platelets study participants. Transfusion 2016 Jun;56(6):1442-50. Epub 2016 Apr 15.
BACKGROUND: 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. STUDY DESIGN AND METHODS: 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). RESULTS: 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. CONCLUSIONS: This work confirms that low- to moderate-level anti-Class I antibodies do not drive PLT rejection, suggesting a role for antibody-independent mechanisms.