PMID- 32429622 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220415 IS - 2287-979X (Print) IS - 2288-0011 (Electronic) IS - 2287-979X (Linking) VI - 55 IP - 2 DP - 2020 Jun 30 TI - Natural soluble human leukocyte antigen class I in donor serum neutralizes donor-specific HLA alloantibodies in recipient serum. PG - 91-98 LID - 10.5045/br.2020.2020031 [doi] AB - BACKGROUND: 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. METHODS: 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. RESULTS: 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), P <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)], P >0.05 for both. CONCLUSION: 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. FAU - Won, Dong Il AU - Won DI AD - Departments of Clinical Pathology, School of Medicine, Kyungpook National University, Daegu, Korea. FAU - Lee, Nan Young AU - Lee NY AD - Departments of Clinical Pathology, School of Medicine, Kyungpook National University, Daegu, Korea. FAU - Lim, Jeong-Hoon AU - Lim JH AD - Departments of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea. FAU - Han, Young Seok AU - Han YS AD - Departments of Surgery, School of Medicine, Kyungpook National University, Daegu, Korea. FAU - Kim, Chan-Duck AU - Kim CD AD - Departments of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea. FAU - Huh, Seung AU - Huh S AD - Departments of Surgery, School of Medicine, Kyungpook National University, Daegu, Korea. LA - eng PT - Journal Article PL - Switzerland TA - Blood Res JT - Blood research JID - 101605247 PMC - PMC7343548 OTO - NOTNLM OT - Donor-specific HLA alloantibody OT - Flow cytometric crossmatch OT - Neutralization OT - Soluble HLA COIS- Authors' Disclosures of Potential Conflicts of Interest No potential conflicts of interest relevant to this article were reported. EDAT- 2020/05/21 06:00 MHDA- 2020/05/21 06:01 PMCR- 2020/06/30 CRDT- 2020/05/21 06:00 PHST- 2020/02/22 00:00 [received] PHST- 2020/04/04 00:00 [revised] PHST- 2020/04/16 00:00 [accepted] PHST- 2020/05/21 06:00 [pubmed] PHST- 2020/05/21 06:01 [medline] PHST- 2020/05/21 06:00 [entrez] PHST- 2020/06/30 00:00 [pmc-release] AID - br.2020.2020031 [pii] AID - BR-55-091 [pii] AID - 10.5045/br.2020.2020031 [doi] PST - ppublish SO - Blood Res. 2020 Jun 30;55(2):91-98. doi: 10.5045/br.2020.2020031.