Nambiar Ashok, Duquesnoy Rene J, Adams Sharon, Zhao Yingdong, Oblitas Jaime, Leitman Susan, Stroncek David, Marincola Francesco
Department of Transfusion Medicine, Bldg 10, 1C711, National Institutes of Health, Bethesda, MD 20892, USA.
Blood. 2006 Feb 15;107(4):1680-7. doi: 10.1182/blood-2004-10-4080. Epub 2005 Nov 3.
This study describes a novel application of HLAMatchmaker to determine platelet compatibility in 16 alloimmunized patients with aplastic anemia refractory to random donor platelet transfusions. HLAMatchmaker is a software algorithm that predicts HLA compatibility by identifying immunogenic epitopes represented by amino acid triplets in antibody-accessible regions of human leukocyte antigen (HLA) molecules and determines the number of triplet mismatches (TMMs) and highly immunogenic triplet mismatches (HIMMs). Corrected count increments (CCIs) and molecular HLA typing were available for 523 transfusions. Conventional compatibility assessment based on cross-reactive group (CREG) determination was not predictive of transfusion outcome. Low HIMMs and TMMs numbers were associated with a higher likelihood of satisfactory (CCIs > or = 8) compared with unsatisfactory (CCIs < 8) outcomes (median HIMMs = 4 vs 6, p2 value < .001; median TMMs = 11 vs 13, p2 value < .001). Although receiver operator characteristic curves revealed that HIMMs or TMMs number are not powerful predictors of individual transfusion outcome, a threshold of at least 3 HIMMs or at least 9 TMMs appeared to be associated with successful transfusions. Triplet-matched transfusions were successful, regardless of CREG matching. Our data validate HLAMatchmaker for platelet transfusions and demonstrate its potential to refine and expand donor selection for HLA-alloimmunized patients.
本研究描述了HLAMatchmaker的一种新应用,用于确定16例对随机供体血小板输注难治的再生障碍性贫血同种免疫患者的血小板相容性。HLAMatchmaker是一种软件算法,通过识别人类白细胞抗原(HLA)分子抗体可及区域中由氨基酸三联体代表的免疫原性表位来预测HLA相容性,并确定三联体错配(TMM)和高免疫原性三联体错配(HIMM)的数量。523次输血可获得校正计数增加值(CCI)和分子HLA分型。基于交叉反应组(CREG)测定的传统相容性评估不能预测输血结果。与不满意(CCI<8)的结果相比,低HIMM和TMM数量与满意(CCI≥8)结果的可能性更高相关(中位HIMM = 4对6,p2值<.001;中位TMM = 11对13,p2值<.001)。尽管受试者工作特征曲线显示HIMM或TMM数量不是个体输血结果的有力预测指标,但至少3个HIMM或至少9个TMM的阈值似乎与成功输血相关。无论CREG匹配如何,三联体匹配的输血都是成功的。我们的数据验证了HLAMatchmaker在血小板输血中的应用,并证明了其在优化和扩大HLA同种免疫患者供体选择方面的潜力。