Elrefaei Mohamed, Narula Tathagat, Alvarez Francisco, Godbey Elizabeth A, Kendrick Jasmine, Criner Gerard, Cordova Francis C, Shigemura Norihisa, Toyoda Yoshiya, Timofeeva Olga
Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL.
Division of Lung Failure and Transplant 2, Mayo Clinic, Jacksonville, FL.
JHLT Open. 2025 May 29;9:100302. doi: 10.1016/j.jhlto.2025.100302. eCollection 2025 Aug.
Antibody-Mediated Rejection (AMR) due to HLA donor-specific antibodies (DSA) is associated with poor outcomes in lung transplant recipients (LTR). AMR treatment using therapeutic plasma exchange (TPE) improves clinical outcomes in LTR. The objective of this study was to assess the clinical utility of 1:16 serum dilution HLA antibody test results as a predictor of response to TPE for de novo DSA (dnDSA) levels and AMR treatment in LTR.
A retrospective analysis of 32 LTR diagnosed with AMR due to dnDSA and treated with TPE was performed at Mayo Clinic (n = 18) and Temple University Hospital (n = 14). HLA antibodies were detected by Luminex single antigen beads assay. Mean Fluorescence Intensity (MFI) levels were measured in undiluted and 1:16 diluted sera before the 1st and after the 5th TPE session. Statistical analysis was performed using GraphPad PRISM software.
Of 32 patients, 14 and 18 patients were diagnosed with early (< 3 months post-transplant) and late (6 months - 3 years post-transplant) AMR respectively. All patients, except one, had HLA Class II dnDSA (97%). In addition, 9/14 (64.2%) and 3/18 (16.6%) of LTR with early and late AMR respectively had HLA class I dnDSA. The MFI for all positive dnDSA in 1:16 diluted sera collected before 1st TPE demonstrated a significant correlation with MFI in undiluted sera collected after 5th TPE in both early (R = 0.8786) and late (R = 0.9045) AMR post-transplant. In addition, MFI in 1:16 diluted pre TPE sera correlated with better overall LTR survival following TPE (p = 0.001).
The MFI of 1:16 serum dilution before 1st TPE may be utilized as a surrogate to predict response to TPE for AMR treatment and overall survival in LTR.
由人类白细胞抗原(HLA)供体特异性抗体(DSA)引起的抗体介导的排斥反应(AMR)与肺移植受者(LTR)的不良预后相关。使用治疗性血浆置换(TPE)进行AMR治疗可改善LTR的临床结局。本研究的目的是评估1:16血清稀释HLA抗体检测结果作为LTR中新生DSA(dnDSA)水平和AMR治疗对TPE反应预测指标的临床实用性。
在梅奥诊所(n = 18)和天普大学医院(n = 14)对32例因dnDSA诊断为AMR并接受TPE治疗的LTR进行回顾性分析。通过Luminex单抗原珠分析法检测HLA抗体。在第1次TPE疗程前和第5次TPE疗程后,分别测量未稀释和1:16稀释血清中的平均荧光强度(MFI)水平。使用GraphPad PRISM软件进行统计分析。
32例患者中,分别有14例和18例被诊断为早期(移植后<3个月)和晚期(移植后6个月 - 3年)AMR。除1例患者外,所有患者均有HLA II类dnDSA(97%)。此外,早期和晚期AMR的LTR分别有9/14(64.2%)和3/18(16.6%)有HLA I类dnDSA。在第1次TPE前收集的1:16稀释血清中,所有阳性dnDSA的MFI与移植后早期(R = 0.8786)和晚期(R = 0.9045)第5次TPE后收集的未稀释血清中的MFI均呈显著相关。此外,第1次TPE前1:16稀释血清中的MFI与TPE后LTR的总体更好生存相关(p = 0.001)。
第1次TPE前1:16血清稀释的MFI可作为预测LTR中AMR治疗对TPE反应及总体生存的替代指标。