Donor‐recipient ethnic mismatching impacts short‐ and long‐term results of heart transplantation

Peled, Yael; Loewenthal, Ron; Kassif, Yigal; Raichlin, Eugenia; Younis, Arwa; Younis, Anan; Nachum, Eyal; Freimark, Dov; Goldenberg, Ilan; Lavee, Jacob

doi:10.1111/ctr.13389

Cited by 2 publications

(1 citation statement)

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“…The higher number of SNVs in race non-concordant transplant donor and recipient compared to raceconcordant transplants may be associated with poorer outcomes. (10,(47)(48)(49). Greater HLA mismatch in race non-concordant transplants is a potential contributor (10,50).…”

Section: Discussionmentioning

confidence: 99%

Donor-derived mitochondrial DNA variant peptides elicit allo-specific immune response in transplant patients

Marishta

Yang

et al. 2020

Preprint

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BACKGROUND: Mitochondrial DNA (mtDNA) nonsynonymous single nucleotide variants (SNVs) between transplant donor stem cells and recipient trigger alloimmune responses and transplant rejection. Whether mt SNVs trigger alloimmune responses in solid-organ transplantation remains unknown, particularly in the background of immunodominant human leukocyte antigens mismatches. This study characterizes mtDNA SNVs and tests if donor-derived mitochondrial peptides trigger alloimmune responses in solid-organ transplantation. METHODS: To count and compare SNVs between donor and recipient (D-R) lung transplant pairs (n = 163), mtDNA was isolated from pre-transplant D-R blood and sequenced. The number of SNVs was compared for D-R demographic groups. We identified nonsynonymous SNVs, constructed 20mer peptides with donor-or recipient-derived amino acid sequences, and used ELISpot assay to test allospecific immune response by interferon gamma (IFNγ) release. To test if similar phenomena occur in other solid-organ transplants, we repeated the analyses in 19 heart transplant D-R pairs. RESULTS: We identified a median of 39 mtDNA SNVs (IQR= 32 -53) per D-R lung transplant pair, of which a median of 6 (IQR = 4 -9) SNVs were nonsynonymous. SNVs were predominantly located at MT-CYB, MT-ATP6, and MT-ND3 genes. The number of SNVs was higher in D-R race non-concordant pairs than in race-concordant pairs, p = 0.015. Donor-derived mt peptides triggered a 19.8-fold higher IFNγ release compared to recipient-derived peptide, p<0.001. Similar findings were observed in heart transplant patients. CONCLUSIONS: Donor-derived mitochondrial peptides trigger allo-specific immune responses after solid-organ transplantation.

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