Impact of one-way HLA matching on GVHD following liver transplantation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17550
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Fujita Health University
• Principal Investigator: Kiguchi Gozo 藤田医科大学, 医学部, 研究員 (00740672)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 肝移植 / GVHD / HLA

Outline of Final Research Achievements

Donor-dominant one-way matching at three human leukocyte antigen (HLA) loci (HLA-A/B/DR) has been suggested to be associated with the development of GVHD, but the exact significance of HLA matching involving HLA-C/DQ/DP remains unclear.
In 75% of cases with GVHD, donor-dominant one-way HLA matching was identified at three loci, HLA-A/B/DR. These cases also showed donor-dominant one-way HLA matching at HLA-C/DQ/DP. 50% of cases with donor-dominant one-way HLA matching at the three HLA-A/B/DR loci developed GVHD. Regardless of HLA-C/DQ/DP matching status, none of the cases with donor-dominant one-way HLA matching at one or two loci of HLA-A/B/DR developed GVHD. To prevent GVHD, it is better not to match donors and recipients with donor-dominant one-way HLA matching at the HLA-A/B/DR 3 locus. HLA-C/DQ/DP have no confirmed effect on GVHD.

Free Research Field

移植外科

Academic Significance and Societal Importance of the Research Achievements

肝移植後のGVHDは稀だが確立された治療法がなく致死的である。HLAホモ接合型のドナーから1ハプロタイプを共有するHLAヘテロ接合型レシピエントへの肝移植はDonor dominant one-way HLA matching（DDOM）と呼ばれ、GVHDのリスクとされてきたが、HLAのローカスごとの意義については明らかにされてこなかった。本研究によりHLA-A, B, DR三座のDDOMは極めてリスクが高いため、そのような組み合わせとなるドナーは避けるべきであることが判明した。また、HLA-C, DQ, DPのDDOMの意義は乏しいと考えられた。