Won Dong Il, Lee Nan Young, Lim Jeong-Hoon, Han Young Seok, Kim Chan-Duck, Huh Seung
Departments of Clinical Pathology, School of Medicine, Kyungpook National University, Daegu, Korea.
Departments of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.
Blood Res. 2020 Jun 30;55(2):91-98. doi: 10.5045/br.2020.2020031.
Human leukocyte antigen (HLA) molecules are cell-bound but can be identified in a soluble form. These soluble HLA (sHLA) molecules have an immunomodulatory function. We investigated whether natural sHLA in donor serum can neutralize donor-specific HLA alloantibodies (DSAs) in recipient serum.
Neutralizing effects of donor serum on DSAs in recipient serum were measured using inhibition assay principle of flow cytometric crossmatch (FCXM), performed using sera from 143 kidney transplant recipients and their donors. The adding of donor serum to recipient serum yielded lower mean fluorescence intensity (MFI) ratios (test/control) than when diluent was added [Roswell Park Memorial Institute (RPMI) or third-party serum], which was presumed to be caused by the neutralizing effects of sHLA.
In the recipient group with class I DSAs alone (N=14), donor serum addition to recipient serum resulted in lower T cell MFI ratios [2.25 (1.31‒32.51)] than those observed on RPMI addition [3.04 (1.33‒125.39), <0.05]. In the recipient group with class II DSAs alone (N=27), donor serum addition showed no significant difference in B cell MFI ratios [5.03 (1.41‒103.53)] compared to diluent addition: RPMI [4.50 (1.34‒145.98)] or third-party serum [5.08 (1.44‒138.47)], >0.05 for both.
Using inhibition FCXM, we verified that natural sHLA class I in donor serum neutralizes DSAs in recipient serum. However, no neutralizing effects of sHLA class II were revealed in this study. These potentially beneficial effects of sHLA infused via blood-derived products should be considered when desensitizing highly HLA-sensitized patients.
人类白细胞抗原（HLA）分子与细胞结合，但也能以可溶性形式被识别。这些可溶性HLA（sHLA）分子具有免疫调节功能。我们研究了供体血清中的天然sHLA是否能中和受体血清中的供体特异性HLA同种抗体（DSA）。
采用流式细胞术交叉配型（FCXM）的抑制试验原理，检测供体血清对受体血清中DSA的中和作用，使用了143例肾移植受者及其供体的血清。与添加稀释剂[罗斯韦尔公园纪念研究所（RPMI）或第三方血清]相比，向受体血清中添加供体血清产生的平均荧光强度（MFI）比值（试验/对照）更低，这被认为是由sHLA的中和作用引起的。
在仅存在I类DSA的受体组（N = 14）中，向受体血清中添加供体血清导致T细胞MFI比值[2.25（1.31 - 32.51）]低于添加RPMI时观察到的比值[3.04（1.33 - 125.39），P < 0.05]。在仅存在II类DSA的受体组（N = 27）中，与添加稀释剂相比，添加供体血清在B细胞MFI比值[5.03（1.41 - 103.53）]上无显著差异：添加RPMI时为[4.50（1.34 - 145.98）]，添加第三方血清时为[5.08（1.44 - 138.47）]，两者P均> 0.05。
通过抑制性FCXM，我们证实供体血清中的天然I类sHLA可中和受体血清中的DSA。然而，本研究未发现II类sHLA的中和作用。在对高度HLA致敏患者进行脱敏治疗时，应考虑通过血液制品输注sHLA的这些潜在有益作用。
