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Here we examined the molecular effects of 6\u2009months of felzartamab treatment on biopsies from the trial using genome-wide microarray analysis, comparing pretreatment, end-of-treatment (week 24) and posttreatment (week 52) biopsies from ten patients treated with felzartamab and ten patients in the placebo group. Felzartamab reduced molecular ABMR activity scores in all nine patients with baseline ABMR activity, selectively suppressing interferon gamma-inducible and natural killer cell transcripts, with minimal effect on ABMR stage-related endothelial transcripts. Suppression was often incomplete when ABMR activity was intense, and molecular recurrence was nearly universal by week 52. However, we also found that felzartamab had parenchymal benefits at week 52, slowing the trajectories of molecular injury scores beyond the treatment period, suggesting that suppression of ABMR activity could potentially slow future progression to kidney failure. These data provide preliminary molecular insights into the effects of CD38-directed treatment for ABMR, which have the potential to inform future therapeutic strategies.<\/jats:p>","DOI":"10.1038\/s41591-025-03653-3","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T05:04:40Z","timestamp":1745903080000},"page":"1668-1676","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Effect of felzartamab on the molecular phenotype of antibody-mediated rejection in kidney transplant biopsies"],"prefix":"10.1038","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6914-9132","authenticated-orcid":false,"given":"Matthias","family":"Diebold","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick T.","family":"Gauthier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2495-790X","authenticated-orcid":false,"given":"Katharina A.","family":"Mayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Mackova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Hinze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5039-2186","authenticated-orcid":false,"given":"Jessica","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6905-6649","authenticated-orcid":false,"given":"Uptal D.","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekkehard","family":"Sch\u00fctz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Jilma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Schrezenmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7929-5942","authenticated-orcid":false,"given":"Klemens","family":"Budde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7600-912X","authenticated-orcid":false,"given":"Georg A.","family":"B\u00f6hmig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1371-1947","authenticated-orcid":false,"given":"Philip F.","family":"Halloran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"3653_CR1","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1084\/jem.167.4.1323","volume":"167","author":"ML Dustin","year":"1988","unstructured":"Dustin, M. L., Singer, K. H., Tuck, D. T. & Springer, T. A. Adhesion of T lymphoblasts to epidermal keratinocytes is regulated by interferon gamma and is mediated by intercellular adhesion molecule 1 (ICAM-1). J. Exp. Med. 167, 1323\u20131340 (1988).","journal-title":"J. Exp. Med."},{"key":"3653_CR2","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1681\/ASN.2020081215","volume":"32","author":"M Mayrdorfer","year":"2021","unstructured":"Mayrdorfer, M. et al. Exploring the complexity of death-censored kidney allograft failure. J. Am. Soc. Nephrol. 32, 1513\u20131526 (2021).","journal-title":"J. Am. Soc. Nephrol."},{"key":"3653_CR3","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.1111\/j.1600-6143.2010.03201.x","volume":"10","author":"LG Hidalgo","year":"2010","unstructured":"Hidalgo, L. G. et al. NK cell transcripts and NK cells in kidney biopsies from patients with donor-specific antibodies: evidence for NK cell involvement in antibody-mediated rejection. Am. J. 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P.F.H. holds shares in Transcriptome Sciences Inc. (TSI), a University of Alberta research company dedicated to developing molecular diagnostics, supported in part by a licensing agreement between TSI and Thermo Fisher Scientific, and by a research grant from Natera, Inc. P.F.H. is a consultant to Natera, Inc. and Argenx BV. G.A.B. is supported by a research grant from Human Immunology Biosciences, Inc. (HI-Bio), South San Francisco, CA, USA, and is member of the steering committee of a planned phase 3 trial evaluating felzartamab in antibody-mediated rejection (Hi-Bio). U.D.P. is an employee and shareholder of Human Immunology Biosciences, acquired by Biogen, and serves as chair for the board of directors of the Kidney Health Initiative. M.D., P.T.G., K.A.M., M.M., C.H., J.C., E.S., B.J., E.S. and K.B. declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}