Pandey Soumya, Harville Terry O
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Ann Clin Lab Sci. 2019 Jan;49(1):50-56.
Pre-transplantation work-up on a patient with end stage renal disease using Single Antigen Bead (SAB) testing showed significant anti-HLA-B44:02 (>5,000 MFI) and anti-HLA-B44:03 (>1,000 MFI) antibodies, with persistence on quarterly testing. No significant Class II anti-HLA antibodies were present. The patient received a potential offer from a living unrelated-donor expressing HLA-B44:02. Based on the presence of anti-HLA-B44:02 antibody, the crossmatch (XM) was predicted to be positive. However, the actual fluorescence cytometry crossmatch (FCXM) was negative. FCXM and Complement Dependent Cytotoxicity-XM (CDC-XM) studies with three surrogate donors who expressed HLA-B44:02 (and no other potential confounding HLA types) were also negative. Additional assays were performed for detecting anti-HLA antibodies. Immucor® LSA® SAB analyses also revealed presence of anti-HLA-B44:02 and anti-HLA-B44:03 antibodies. However, One Lambda® Antigen Trays, C1q analysis, and iBeads®, did not detect elevated anti-HLA-B44:02 and/or anti-HLA-B44:03 antibodies. An extensive evaluation of all exposed and non-exposed epitopes expressed by the patient and the donor was performed to identify the non-shared epitopes between them. The donor specific antibody (DSA) pattern detected would be expected to conform to non-shared epitopes; however, non-shared "exposed" epitopes were not present in the DSA antibody pattern. Whereas, the apparent DSA antibody pattern consisted of antibodies to "non-exposed" epitopes. Altogether, it was concluded that the anti-HLA-B44:02 antibody detected by SAB testing was directed against some denatured component(s) (non-exposed) of the HLA antigen attached to the SAB, and would not be clinically significant. The patient received the transplant and the post-transplant course has been uneventful for greater than 5 years. This case emphasizes: (1) A significant number of SAB may have denatured HLA molecules attached to them (2) The DSA and non-DSA anti-HLA antibody patterns should be evaluated for the expected epitope components to determine the clinical relevance. Additional testing should be considered to help with these analyses (3) The FCXM remains the "gold standard" for making the final decision to transplant, since the "stringent" use of a "predicted" positive XM using apparent DSA detected by SAB analysis may exclude XM-compatible donors.
对一名终末期肾病患者进行移植前检查，采用单抗原珠（SAB）检测显示存在显著的抗HLA - B44:02（>5,000 MFI）和抗HLA - B44:03（>1,000 MFI）抗体，且在每季度检测中持续存在。不存在显著的II类抗HLA抗体。该患者收到了一位表达HLA - B44:02的非亲属活体供体的潜在供肾。基于抗HLA - B44:02抗体的存在，预计交叉配型（XM）为阳性。然而，实际的荧光细胞术交叉配型（FCXM）为阴性。对三名表达HLA - B44:02（且无其他潜在混淆HLA类型）的替代供体进行的FCXM和补体依赖细胞毒性交叉配型（CDC - XM）研究也为阴性。进行了额外的检测以检测抗HLA抗体。Immucor® LSA® SAB分析也显示存在抗HLA - B44:02和抗HLA - B44:03抗体。然而，One Lambda®抗原板、C1q分析和iBeads®未检测到抗HLA - B44:02和/或抗HLA - B44:03抗体升高。对患者和供体表达的所有暴露和未暴露表位进行了广泛评估，以确定它们之间的非共享表位。检测到的供体特异性抗体（DSA）模式预计应符合非共享表位；然而，DSA抗体模式中不存在非共享的“暴露”表位。相反，明显的DSA抗体模式由针对“未暴露”表位的抗体组成。总之，得出的结论是，SAB检测到的抗HLA - B44:02抗体针对的是附着在SAB上的HLA抗原的一些变性成分（未暴露），在临床上不具有重要意义。该患者接受了移植，移植后超过5年病情平稳。该病例强调：（1）大量SAB可能附着有变性的HLA分子；（2）应评估DSA和非DSA抗HLA抗体模式中的预期表位成分，以确定临床相关性。应考虑进行额外检测以辅助这些分析；（3）FCXM仍然是做出最终移植决定的“金标准”，因为使用SAB分析检测到的明显DSA“预测”阳性XM的“严格”应用可能会排除与XM相容的供体。
