PMID- 38274830 OWN - NLM STAT- MEDLINE DCOM- 20240129 LR - 20240406 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 14 DP - 2023 TI - HLA-DPB1 genotype variants predict DP molecule cell surface expression and DP donor specific antibody binding capacity. PG - 1328533 LID - 10.3389/fimmu.2023.1328533 [doi] LID - 1328533 AB - The contribution of alloresponses to mismatched HLA-DP in solid organ transplantation and hematopoietic stem cell transplantation (HCT) has been well documented. Exploring the regulatory mechanisms of DPB1 alleles has become an important question to be answered. In this study, our initial investigation focused on examining the correlation between the rs9277534G/A SNP and DPB1 mRNA expression. The result showed that there was a significant increase in DPB1 mRNA expression in B lymphoblastoid cell lines (BLCLs) with the rs9277534GG genotype compared to rs9277534AA genotype. In addition, B cells with the rs9277534GG exhibited significantly higher DP protein expression than those carrying the rs9277534AA genotype in primary B cells. Furthermore, we observed a significant upregulation of DP expression in B cells following treatment with Interleukin 13 (IL-13) compared to untreated B cells carrying rs9277534GG-linked DPB1 alleles. Fluorescence in situ hybridization (FISH) analysis of DPB1 in BLCL demonstrated significant differences in both the cytoplasmic (p=0.0003) and nuclear (p=0.0001) localization of DP mRNA expression comparing DPB1*04:01 (rs9277534AA) and DPB1*05:01 (rs9277534GG) homozygous cells. The study of the correlation between differential DPB1 expression and long non-coding RNAs (lncRNAs) showed that lnc-HLA-DPB1-13:1 is strongly associated with DP expression (r=0.85), suggesting the potential involvement of lncRNA in regulating DP expression. The correlation of DP donor specific antibody (DSA) with B cell flow crossmatch (B-FCXM) results showed a better linear correlation of DP DSA against GG and AG donor cells (R(2) = 0.4243, p=0.0025 and R(2) = 0.6172, p=0.0003, respectively), compared to DSA against AA donor cells (R(2) = 0.0649, p=0.4244). This explained why strong DP DSA with a low expression DP leads to negative B-FCXM. In conclusion, this study provides evidence supporting the involvement of lncRNA in modulating HLA-DP expression, shedding lights on the intricate regulatory mechanisms of DP, particularly under inflammatory conditions in transplantation. CI - Copyright (c) 2024 Yin, Soe, Valenzuela, Reed and Zhang. FAU - Yin, Yuxin AU - Yin Y AD - UCLA Immunogenetics Center, Department of Pathology & Laboratory Medicine, Los Angeles, CA, United States. FAU - Soe, Nwe Nwe AU - Soe NN AD - Department of Pathology, AdventHealth Tissue Typing Laboratory, Orlando, FL, United States. FAU - Valenzuela, Nicole M AU - Valenzuela NM AD - UCLA Immunogenetics Center, Department of Pathology & Laboratory Medicine, Los Angeles, CA, United States. FAU - Reed, Elaine F AU - Reed EF AD - UCLA Immunogenetics Center, Department of Pathology & Laboratory Medicine, Los Angeles, CA, United States. FAU - Zhang, Qiuheng AU - Zhang Q AD - UCLA Immunogenetics Center, Department of Pathology & Laboratory Medicine, Los Angeles, CA, United States. LA - eng PT - Journal Article DEP - 20240111 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (HLA-DPB1 antigen) RN - 0 (RNA, Long Noncoding) RN - 0 (HLA-DP beta-Chains) RN - 0 (Antibodies) RN - 0 (RNA, Messenger) SB - IM MH - Humans MH - In Situ Hybridization, Fluorescence MH - *RNA, Long Noncoding MH - HLA-DP beta-Chains/genetics MH - Genotype MH - Antibodies/genetics MH - Unrelated Donors MH - RNA, Messenger PMC - PMC10808447 OTO - NOTNLM OT - HLA-DPB1 OT - crossmatch OT - hematopoietic stem cell transplantation OT - long non-coding RNA OT - rs9277534 OT - transplantation COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/01/26 06:44 MHDA- 2024/01/29 06:44 PMCR- 2023/01/01 CRDT- 2024/01/26 03:59 PHST- 2023/10/26 00:00 [received] PHST- 2023/12/21 00:00 [accepted] PHST- 2024/01/29 06:44 [medline] PHST- 2024/01/26 06:44 [pubmed] PHST- 2024/01/26 03:59 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2023.1328533 [doi] PST - epublish SO - Front Immunol. 2024 Jan 11;14:1328533. doi: 10.3389/fimmu.2023.1328533. eCollection 2023.