{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T20:30:14Z","timestamp":1785875414878,"version":"3.56.0"},"reference-count":29,"publisher":"American Society for Clinical Investigation","issue":"3","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":69,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["AI116814,AI154845"],"award-info":[{"award-number":["AI116814,AI154845"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["AI176507"],"award-info":[{"award-number":["AI176507"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","award":["HL148528"],"award-info":[{"award-number":["HL148528"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,2]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Cardiac 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We 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 Fe\n                      <jats:sup>2+<\/jats:sup>\n                      in heart explants with CAV.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      A majority of graft-derived mAb (21 of 37; approximately 57%) \u2014 but none of the mAb derived from blood PC \u2014 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 Fe\n                      <jats:sup>2+<\/jats:sup>\n                      ion in the media of arteries with hyperplasia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>These 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>Grants AI116814, AI154845, AI184963, and AI176507, HL148528, RYC2022-036797-I, P30CA013696, UL1TR001873, S10OD020056.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci194138","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T17:00:46Z","timestamp":1764090046000},"source":"Crossref","is-referenced-by-count":4,"title":["Dominant intragraft plasma cells targeting bilirubin implicate local heme catabolism in human cardiac allograft vasculopathy"],"prefix":"10.1172","volume":"136","author":[{"given":"Sarah B.","family":"See","sequence":"first","affiliation":[{"name":"Columbia University Irving Medical Center, 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