{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:57:45Z","timestamp":1787313465335,"version":"build-2736575974"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009091","name":"Justus Liebig Universit\u00e4t Gie\u00dfen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009091","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>An increased risk of severe infectious disease and acute antibody-mediated rejection (AMR) has been described after ABOi renal transplantation. We performed a prospective renal transplant study up to 5 years posttransplant to detect long-term immunological effects of rituximab administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Mononuclear cell subsets in peripheral blood, regional lymph nodes and protocol biopsies,\n                      <jats:italic>in-vitro<\/jats:italic>\n                      T and B cell responses, serum sCD30 and neopterin were assessed in 85 renal transplant recipients (living donation: n=25 ABOi, n=30 ABO compatible (ABOc); deceased donation (DD): n=30, all ABO compatible), and IgG anti-HLA antibodies by single antigen assay in ABOc and ABOi patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      An increased frequency of severe infectious diseases in ABOi recipients (doubled versus ABOc within 2 years, P = 0.042) coincided with profoundly downregulated peripheral blood B cell subsets for at least 2 years, impaired\n                      <jats:italic>in-vitro<\/jats:italic>\n                      B cell responses (T-dependent: 2 years, versus ABOc: P = 0.004) and significantly lower CD4+ and CD8+ T cell counts (versus ABOc; 6 months, P = 0.046 and 3 months, P = 0.011, respectively). In regional lymph nodes, we found a significant downregulation of naive B cells (P = 0.031) and short lived plasma cells (P&amp;lt;0.0005) at the time of transplantation. In protocol graft biopsies, rituximab induced B cell depletion at 3 months (P&amp;lt;0.001), but counter-regulatory enhanced counts of T cells (P = 0.041), macrophages (P = 0.021) and plasma cells (P = 0.033) at 1 year. This immune activation was associated with a temporary rise in neopterin levels (P \u2264 0.024 versus ABOc, day 14 until 1 year), CD4 helper activity (P = 0.019 versus ABOc at 2 years) and NK cell counts (P = 0.034 versus ABOc, 4 years; P \u2264 0.040 versus DD, 3\u20135 years), a missing impact of rituximab on sCD30 levels and HLA antibody formation, and an increased frequency of biopsy-proven acute rejection (3\u201312 months, P = 0.003) and AMR (P = 0.008 within 5 years).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>An increased frequency of severe infectious diseases in ABOi renal transplant recipients may be explained by rituximab-induced long-term immunological effects on CD4+ and CD8+ T cell counts and the prolonged depletion of B cell subsets together with compromised B cell responses. In protocol graft biopsies, rituximab induced early B cell depletion but counter-regulatory proinflammatory effects coinciding with an increased acute rejection frequency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration Details<\/jats:title>\n                    <jats:p>ClinicalTrials.gov, identifier NCT01136395; EudraCT, identifier No.: 2009-012198-36.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1706158","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T05:14:54Z","timestamp":1765516494000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Long-term compromised immune regulation after rituximab induction in blood group incompatible (ABOi) living-donor renal transplantation \u2013 5 year results of a prospective pilot study"],"prefix":"10.3389","volume":"16","author":[{"given":"Rolf","family":"Weimer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hristos","family":"Karakizlis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Renner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"Dietrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Daniel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caner","family":"S\u00fcsal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Sch\u00fcttler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"K\u00e4mper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Leicht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"W\u00f6rlen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Milchsack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lene","family":"Renner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Stich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann-Josef","family":"Gr\u00f6ne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Hecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00fcdiger","family":"H\u00f6rbelt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winfried","family":"Padberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Opelz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000000312","article-title":"Three-year outcomes following 1,420 ABO-incompatible living-donor kidney transplants performed after ABO antibody reduction: results from 101 centers","volume":"99","author":"Opelz","year":"2015","journal-title":"Transplantation"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.00540118","article-title":"ABO-incompatible kidney transplant outcomes","volume":"13","author":"de Weerd","year":"2018","journal-title":"A meta-analysis. 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