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28 ASHI Quarterly Third Quarter 2015 S C I E N T I F I C C O M M U N I C A T I O N S the UA antigen list in UNet for all thoracic transplant candidates and for patients undergoing desensitization where either the window of opportunity for transplant is short or the luxury of time on the waitlist does not exist 4 Developing sensitive methods to distinguish complement activating from non-activating antibodies will benefit the pre- transplant work-up Almahri et al recently reported that deposition of complement factors were detected on T and B lymphocytes which co-purified with endothelial precursor cells (EPC) in the flow cytometry based EPC XM assay 19 In this study, the specificity and sensitivity for C3d deposition on EPC XM co-purified with T cells vs the T cell CDC XM were 69% and 72%, respectively However, C3d deposition on EPC XM co-purified with B cells had high specificity (86%), but considerably lower sensitivity (39%) than the B cell CDC XM The authors also developed a flow cytometry based method (FCtox) that enables simultaneous detection of cytotoxicity and HLA antibody binding 20 The assay was comparable with conventional CDC and FCXM results as well as the presence of IgG and C1q activating antibodies Incorporating cytotoxicity methods in the more sensitive FCXM protocol could be the promising start to potentially minimize the number of assays needed in the work-up prior to kidney transplantation References 1 Rebibou JM, Bittencourt MC, Saint-Hillier Y, et al T-cell flow- cytometry crossmatch and long term renal graft survival Clin Transplant. 2004;18(5):558-63 2 Karpinski M, Rush D, Jeffrey J, et al Flow cytometric crossmatching in primary renal transplant recipients with a negative anti-human globulin enhanced cytotoxicity crossmatch J Am Soc Nephrol. 2001;12(12):2807-14 3 Paul JM Increased utilization of flow cytometry in HLA crossmatching reported in CAP Proficiency Testing NewsPath, College of American Pathologists Posted November 12, 2008 4 Chen G, Sequeira F, Tyan DB Novel C1q assay reveals a clinically relevant subset of HLA antibodies independent of IgG strength on single antigen beads Hum Immunol. 2011;72:849-58 5 Lachmann N, Todorova K, Schulze H, Schonemann C Systemic Comparison of four Cell- and Luminex-based methods for assessment of complement-activating HLA antibodies Transplantation 2014;95:694-700 6 Loupy A, Lefaucheur C, Vernerey D, et al Complement-binding anti-HLA antibodies and kidney-allograft survival N Engl J Med. 2013;369(13):1215-26 7 Racusen L, Leffell M C1q-binding antibodies in kidney transplantation N Engl J Med. 2013;369(13):1266 8 Tinckam K, Heeger P Complementing donor-specific antibody testing Nat Rev Nephrol. 2013;9:713-14 9 Crespo M, Torio A, Mas V, et al Clinical relevance of pretransplant anti-HLA donor-specific antibodies: Does C1q-fixation matter? Transplant Immunol. 2013;29:28-33 10 Otten HG, Verhaar MC, Borsta HPE, Heneb RJ, van Zuilenb AD Pretransplant donor-specific HLA class I and II antibodies are associated with an increased risk for kidney graft failure Am J Transplant. 2012;12:1618-23 11 Baid-Agrawal S, Lachmann N, Budde K Letter to the editor N Engl J Med. 2014;370(1):84 12 Roumenina LT, Radanova M, Atanasov BP, et al Heme interacts with C1q and inhibits the classical complement pathway J Bio Chem. 2011;286(18)16459-69 13 Arriaga SM, Basiglio CL, Mottino AD, Almara AM Unconjugated bilirubin inhibits C1 esterase activity Clin Biochem. 2009;42(9):919- 21 14 Basiglio CL, Arriaga SM, Pelusa HF, Almara AM, Roma MG, Mottino AD Protective role of unconjugated bilirubin on complement-mediated hepatocytolysis Biochi Biophys Acta. 2007;1770(7):1003-10 15 Niven IP, Whaley K Inhibition of C1q binding to antigen-antibody complexes by a factor in rheumatoid arthritis serum Rheumatoid Int. 1986;6:205-8 16 Lobo P, Spencer C, Brayman K Letter to the editor N Engl J Med. 2014;370(1):83-84 17 Thammanichanond D, Mongkolsuk T, Rattanasiri S, et al Significance of C1q-fixing DSA after kidney transplantation Transplant Proc. 2014;46:368-71 18 Daha NA, Banda MK, Roos A, et al Complement activation by (auto-) antibodies Mol Immunol. 2011;48:1656-65 19 Almahri A, Holgersson J, Alheim M Detection of complement- fixing and non-fixing antibodies specific for endothelial precursor cells and lymphocytes using flow cytometry Tissue Antigens. 2012;80:404-15 20 Alheim M, Paul PK, Hauzenberger DM, Wikstrom AC Evaluation of a new cytometry crossmatch procedure for simultaneous detection of cytotoxicity and antibody binding Tissue Antigens. 2013;82:125-30 Corresponding Author Information Clinical Immunogenetics Laboratory, Seattle Cancer Care Alliance Phone: 206-288-6663 E-mail: gbalgans@seattlecca org