ArticleThe Journal of clinical investigation2026
Dominant intragraft plasma cells targeting bilirubin implicate local heme catabolism in human cardiac allograft vasculopathy.
Article in The Journal of clinical investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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Who cites it
2 citing papers in PubMed.
- Autoreactive antibody production by intrarenal B cells in mouse kidney allograft rejection.bioRxiv : the preprint server for biology · 2026Article
- Heme disposal inside heart transplants: a trigger for rejection?The Journal of clinical investigation · 2026Article
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Authors and funding
25 authors.
Funding
Abstract
BACKGROUNDCardiac allograft vasculopathy (CAV) is consistently accompanied by immune infiltrates surrounding affected coronary arteries, including antibody-producing plasma cells (PC). The antigenic drivers of these intragraft PC responses remain poorly defined.METHODSWe characterized graft infiltrating PC by single-cell RNA sequencing and immunoglobulin gene profiling. Using immunoglobulin sequences, we generated 37 recombinant monoclonal antibodies (mAb) from dominant intragraft PC clones and 24 control mAb from peripheral blood PC. Antigen reactivity was screened against chemical adducts, including bilirubin, a heme-degradation byproduct. Histologic and tissue analyses assessed bilirubin deposition as well as expression of hemecatabolic enzymes and the presence of Fe2+ in heart explants with CAV.RESULTSA majority of graft-derived mAb (21 of 37; approximately 57%) - but none of the mAb derived from blood PC - reacted to bilirubin. Bilirubin deposition was detected within lymphocytic aggregates in CAV grafts. In coronary arteries with CAV lesions, bilirubin accumulated in the cytoplasm and nuclei of smooth muscle cells in the tunica media, a pattern not observed in healthy heart tissue. Lastly, we detected the expression of heme-oxygenase-1 and biliverdin reductases in graft-infiltrating macrophages along with the presence of Fe2+ ion in the media of arteries with hyperplasia.CONCLUSIONThese findings suggest that local heme catabolism and resultant bilirubin accumulation create a prominent target for intragraft antibody responses in CAV. Bilirubin-specific antibodies and hemecatabolic pathways may contribute to CAV pathogenesis and represent potential mechanistic and therapeutic avenues for further investigation.FUNDINGGrants AI116814, AI154845, AI184963, and AI176507, HL148528, RYC2022-036797-I, P30CA013696, UL1TR001873, S10OD020056.
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