Résumé
【Objective】 To analyze differences of eplets between the patient who generated HLA allele-specific antibodies after platelet transfusion with donors. 【Methods】 The HLA genotypes of the patient and donors were detected by PCR-SBT, and the Luminex single antigen beads coating was used to screen HLA-Ⅰ antibodies in the patient’s serum. HLA Matchmaker was utilized to analyze different amino acids and eplets. 【Results】 The patient carried HLA-A*02∶03 allele, and HLA-A2 antibodies were found in his serum after platelet transfusion (A*02∶01, A*02∶06, and A*02∶07). Sequence alignment showed that the patient′s A*02∶03 has a difference in position 149, which resulted in a different eplet between A*02∶03 and A*02∶01, A*02∶06, A*02∶07 and then induced the production of antibodies. 【Conclusion】 HLA antibodies are specific for HLA epitopes that have structural differences due to amino acid differences between HLA alleles, suggesting that high-resolution typing of HLA-A, -B need to be conducted in patients and donors, and the acceptable mismatch of HLA should be determined based on epitopes rather than antigens, so as to reduce alloimmune response and improve platelet count after transfusion.
Résumé
【Objective】 To analyze the factors affecting the efficacy of platelet transfusion and the specificity of HLA-Ⅰ antibodies in tumor patients. 【Methods】 Tumer patients applied for platelet transfusion from November 2019 to July 2021 in Sichuan Cancer Hospital province were screened for platelet antibodies. The transfusion efficacy was evaluated and its influencing factors were analyzed, Antibody positive patients were detected for HLA-Ⅰ antibodies. 【Results】 The positive rates of platelet antibody and HLA-Ⅰ antibody, as well as the platelet transfusion refractoriness rate were 35.2%(50/142), 32.4%(46/142) and 16.9%(24/142), respectively. The platelet refractoriness rate of platelet antibody positive patients was higher than that of platelet antibody negative patients [30.0%(15/50) vs 9.8%(9/92)] (χ2=9.428, P<0.05). Multivariate logistic results showed that gender (χ2=12.608, P<0.001, OR=3.800, 95%CI: 1.819-7.940) was an independent risk factor for platelet antibody production, and platelet antibody(χ2=8.648, P<0.05, OR=3.952, 95%CI: 1.581~9.878) was the independent risk factor for transfusion efficacy. The detection rates of strong positive, positive and weak positive HLA-I antibodies were 69.6% (32/46), 80.4% (37/46) and 97.8% (45/46), respectively. The antibodies with high detection rate were anti-B*15∶12, anti-B*57∶03, anti-B*57∶01, anti-B*13∶02, anti-B*49∶01, anti-B*50∶01, anti-A*25∶01, anti-B*15∶01, anti-B*15∶02 and anti-B*44∶02. There were 19 kinds of HLA-Ⅰ antibodies with MFI≥10 000, including anti-A*02∶01, anti-A*02∶03 and anti-A*02∶06. The CCI values were lower in HLA-Ⅰ antibody positive patients(n=46) than in HLA-I antibody negative patients(n=96) by Wilcoxon test (P<0.05). 【Conclusion】 Among tumor patients who received platelet transfusion, gender(female) was the risk factor for platelet antibody production. Platelet antibody positive patients were prone to platelet transfusion refractoriness. HLA-Ⅰ antibodies were the main platelet antibodies, suggesting that HLA-Ⅰ gene matching platelets could improve the efficacy of platelet transfusion.
Résumé
【Objective】 To analyze the specificity and Eplets of HLA allele-specific antibody in patients with platelet transfusion refractoriness (PTR). 【Methods】 HLA-A and B genotypes were detected by PCR-SBT, and HLA-Ⅰ antibodies in patients′ serum were detected by Luminex single antigen beads coating method. IPD-IMGT/HLA Database was used to find the differential amino acids of allele-specific antibodies, and HLA Eplet database was used to analyze the registry Eplets. 【Results】 HLA allele-specific antibodies were found in 12 out of 82 patients with PTR.After sequence alignment, a total of 18 differential amino acids were found, such as 19E>19K, 166D>116E, 167G>167W and so on. Among these differential amino acids, 16 registry Eplets were retrieved such as 19E>19K, 95I>95L, 113YD>113HD and so on.The amino acid substitution of 166DG>166EW, 70Q>70H, 67S>67Y, 94I>94T, 82LR>82RG, and 211G>211A may form new Eplets that have not been registered.The antigens of A11, A24, B15, B27 and B38 can be further subdivided into HLA narrow specific antigens. 【Conclusion】 It was found that there were HLA allele-specific antibodies in patients with PTR, suggesting that high-resolution typing of HLA-A, B should be carried out for these patients and platelet donors in HLA compatible transfusion of PTR.