{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:56:34Z","timestamp":1753890994958,"version":"3.41.2"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T00:00:00Z","timestamp":1641254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Application of anti-thymocyte globulin (ATG) is a widely used strategy for the prevention of graft-versus-host disease (GvHD). As vitamin D3 serum levels are also discussed to affect hematopoietic stem cell transplantation (HSCT) outcome and GvHD development, we analysed a possible interplay between ATG treatment and serum levels of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 in 4 HSCT cohorts with different vitamin D3 supplementation. ATG is significantly associated with higher serum level of 1,25-dihydroxyvitamin D3 around HSCT (day -2 to 7, peri-transplant), however only in patients with adequate levels of its precursor 25-hydroxyvitamin D3. ATG exposure had no impact on overall survival in patients supplemented with high dose vitamin D3, but was associated with higher risk of one-year treatment-related mortality (log rank test p=0.041) in patients with no\/low vitamin D3 supplementation. However, the difference failed to reach significance applying a Cox-model regression without and with adjustment for baseline risk factors (unadjusted P=0,058, adjusted p=0,139). To shed some light on underlying mechanisms, we investigated the impact of ATG on 1,25-Dihydroxyvitamin D3 production by human dendritic cells (DCs) <jats:italic>in vitro.<\/jats:italic> ATG increased gene expression of <jats:italic>CYP27B1<\/jats:italic>, the enzyme responsible for the conversion of 25-hydroxyvitamin D3 into 1,25-dihydroxyvitamin D3, which was accompanied by higher 1,25-dihydroxyvitamin D3 levels in ATG-treated DC culture supernatants. Our data demonstrate a cooperative effect of 25-hydroxyvitamin D3 and ATG in the regulation of 1,25-dihydroxyvitamin D3 production. This finding may be of importance in the context of HSCT, where early high levels of 1,25-dihydroxyvitamin D3 levels have been shown to be predictive for lower transplant related mortality and suggest that vitamin D3 supplementation may especially be important in patients receiving ATG for GvHD prophylaxis.<\/jats:p>","DOI":"10.3389\/fimmu.2021.803726","type":"journal-article","created":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T06:06:50Z","timestamp":1641276410000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Anti-Thymocyte Globulin Treatment Augments 1,25-Dihydroxyvitamin D3 Serum Levels in Patients Undergoing Hematopoietic Stem Cell Transplantation"],"prefix":"10.3389","volume":"12","author":[{"given":"Carina","family":"Matos","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin","family":"Peter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Weich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Peuker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Schoenhammer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Roider","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sakhila","family":"Ghimire","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Babl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonja","family":"Decking","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"G\u00fcllstorf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolaus","family":"Kr\u00f6ger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrin","family":"Hammon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Herr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Stark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iris M.","family":"Heid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrin","family":"Renner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernst","family":"Holler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Kreutz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1609337","article-title":"Acute Graft-Versus-Host Disease - Biologic Process, Prevention, and Therapy","volume":"377","author":"Zeiser","year":"2017","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-018-0393-0","article-title":"Antithymocyte Globulin for Graft-Versus-Host Disease Prophylaxis: An Updated Systematic Review and Meta-Analysis","volume":"54","author":"Kumar","year":"2019","journal-title":"Bone Marrow Transplant"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2014.11.676","article-title":"Rabbit Anti-T Cell Globulin in Allogeneic Hematopoietic Cell Transplantation","volume":"21","author":"Storek","year":"2015","journal-title":"Biol Blood Marrow Transplant"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/jebm.12383","article-title":"Vitamin D Deficiency Is Not Associated With Graft Versus Host Disease After Hematopoietic Stem Cell Transplantation: A Meta-Analysis","volume":"13","author":"Chiengthong","year":"2020","journal-title":"J Evid Based Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.73.0085","article-title":"Pretransplant Vitamin D Deficiency Is Associated With Higher Relapse Rates in Patients Allografted for Myeloid Malignancies","volume":"35","author":"Radujkovic","year":"2017","journal-title":"J Clin Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.08.034","article-title":"Monocyte-Derived Cells Express CYP27A1 and Convert Vitamin D3 Into its Active Metabolite","volume":"349","author":"Gottfried","year":"2006","journal-title":"Biochem Biophys Res Commun"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.4.1300.1300","article-title":"1,25-Dihydroxyvitamin D3 Production and Vitamin D3 Receptor Expression Are Developmentally Regulated During Differentiation of Human Monocytes Into Macrophages","volume":"82","author":"Kreutz","year":"1993","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-11-3521","article-title":"Regulation of 25-Hydroxyvitamin D3-1 Alpha-Hydroxylase and Production of 1 Alpha,25-Dihydroxyvitamin D3 by Human Dendritic Cells","volume":"102","author":"Fritsche","year":"2003","journal-title":"Blood"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2011.03482.x","article-title":"Vitamin D3: A Helpful Immuno-Modulator","volume":"134","author":"Di Rosa","year":"2011","journal-title":"Immunology"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-020-01031-w","article-title":"1,25-Dihydroxyvitamin-D3 But Not the Clinically Applied Marker 25-Hydroxyvitamin-D3 Predicts Survival After Stem Cell Transplantation","volume":"56","author":"Peter","year":"2021","journal-title":"Bone Marrow Transplant"},{"key":"B11","article-title":"Adoptive Transfer of Tumor Cytotoxic Macrophages Generated In Vitro From Circulating Blood Monocytes: A New Approach to Cancer Immunotherapy","volume":"50","author":"Andreesen","year":"1990","journal-title":"Cancer Res"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.D058511","article-title":"Accurate and Reliable Quantification of 25-Hydroxy-Vitamin D Species by Liquid Chromatography High-Resolution Tandem Mass Spectrometry","volume":"56","author":"Liebisch","year":"2015","journal-title":"J Lipid Res"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.22143","article-title":"High Incidence of Vitamin D Deficiency in Patients Undergoing Allogeneic Stem Cell Transplantation","volume":"86","author":"Joseph","year":"2011","journal-title":"Am J Hematol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2015.123","article-title":"Increased Incidence of Chronic GvHD and CMV Disease in Patients With Vitamin D Deficiency Before Allogeneic Stem Cell Transplantation","volume":"50","author":"von Bahr","year":"2015","journal-title":"Bone Marrow Transplant"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1042\/cs0860627","article-title":"Cyclosporin A and Vitamin D Metabolism: Studies in Patients With Psoriasis and in Rats","volume":"86","author":"Shaw","year":"1994","journal-title":"Clin Sci (Lond)"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m111.244061","article-title":"Dexamethasone Enhances 1alpha,25-Dihydroxyvitamin D3 Effects by Increasing Vitamin D Receptor Transcription","volume":"286","author":"Hidalgo","year":"2011","journal-title":"J Biol Chem"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1021\/pr200724e","article-title":"Differential Protein Pathways in 1,25-Dihydroxyvitamin D3 and Dexamethasone Modulated Tolerogenic Human Dendritic Cells","volume":"11","author":"Ferreira","year":"2012","journal-title":"J Proteome Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.12.4659.bloodjournal88124659","article-title":"Myeloma Cell Growth Arrest, Apoptosis, and Interleukin-6 Receptor Modulation Induced by EB1089, Vitamin D3 Derivative, Alone or in Association With Dexamethasone","volume":"88","author":"Puthier","year":"1996","journal-title":"Blood"},{"key":"B19","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1159\/000350328","article-title":"Tolerogenic Dendritic Cells: Key Regulators of Peripheral Tolerance in Health and Disease","volume":"161","author":"Saei","year":"2013","journal-title":"Int Arch Allergy Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1189\/jlb.0613336","article-title":"Tolerogenic Dendritic Cells: Molecular and Cellular Mechanisms in Transplantation","volume":"95","author":"Svajger","year":"2014","journal-title":"J Leukocyte Biol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2018.11.011","article-title":"Vitamin D Controls the Capacity of Human Dendritic Cells to Induce Functional Regulatory T Cells by Regulation of Glucose Metabolism","volume":"187","author":"Vanherwegen","year":"2019","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17122081","article-title":"Antithymocyte Globulin Induces a Tolerogenic Phenotype in Human Dendritic Cells","volume":"17","author":"Roider","year":"2016","journal-title":"Int J Mol Sci"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.11.5382","article-title":"Differential Regulation of Vitamin D Receptor and its Ligand in Human Monocyte-Derived Dendritic Cells","volume":"170","author":"Hewison","year":"2003","journal-title":"J Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/s1567-5769(02)00049-8","article-title":"Immunomodulatory Effects of Vitamin D Receptor Ligands in Autoimmune Diseases","volume":"2","author":"Adorini","year":"2002","journal-title":"Int Immunopharmacol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-011-9599-2","article-title":"Anti-T Lymphocyte Globulin (ATG) Induces Generation of Regulatory T Cells, at Least Part of Them Express Activated CD44","volume":"32","author":"Shimony","year":"2012","journal-title":"J Clin Immunol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1159\/000328874","article-title":"Effects of Cyclosporine, Tacrolimus and Rapamycin on Renal Calcium Transport and Vitamin D Metabolism","volume":"34","author":"Lee","year":"2011","journal-title":"Am J Nephrol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/BF03259279","article-title":"Corticosteroids in Rheumatoid Arthritis","volume":"3","author":"Bijlsma","year":"1995","journal-title":"Clin Immunotherapeutics"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21579","article-title":"Dexamethasone Suppresses Allergic Rhinitis and Amplifies CD4(+) Foxp3(+) Regulatory T Cells In Vitro","volume":"5","author":"Wang","year":"2015","journal-title":"Int Forum Allergy Rhinol"},{"key":"B29","first-page":"4164","article-title":"Combination of 1\u03b1,25-Dihydroxyvitamin D&lt;sub<3&lt;\/sub< With Dexamethasone Enhances Cell Cycle Arrest and Apoptosis","volume":"7","author":"Bernardi","year":"2001","journal-title":"Clin Cancer Res"},{"volume-title":"Dexamethasone","year":"2020","author":"Johnson","key":"B30"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2018.7036","article-title":"Stimulation of Tolerogenic Dendritic Cells Using Dexamethasone and 1,25-Dihydroxyvitamin D3 Represses Autologous T Cell Activation and Chondrocyte Inflammation","volume":"17","author":"Wang","year":"2019","journal-title":"Exp Ther Med"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1640339","article-title":"Regulation of Vitamin D-1alpha-Hydroxylase and -24-Hydroxylase Expression by Dexamethasone in Mouse Kidney","volume":"164","author":"Akeno","year":"2000","journal-title":"J Endocrinol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70225-6","article-title":"Standard Graft-Versus-Host Disease Prophylaxis With or Without Anti-T-Cell Globulin in Haematopoietic Cell Transplantation From Matched Unrelated Donors: A Randomised, Open-Label, Multicentre Phase 3 Trial","volume":"10","author":"Finke","year":"2009","journal-title":"Lancet Oncol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1056\/NEJMoa1506002","article-title":"Antilymphocyte Globulin for Prevention of Chronic Graft-Versus-Host Disease","volume":"374","author":"Kr\u00f6ger","year":"2016","journal-title":"N Engl J Med"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(17)30029-7","article-title":"Association Between Anti-Thymocyte Globulin Exposure and Survival Outcomes in Adult Unrelated Haemopoietic Cell Transplantation: A Multicentre, Retrospective, Pharmacodynamic Cohort Analysis","volume":"4","author":"Admiraal","year":"2017","journal-title":"Lancet Haematol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00315","article-title":"Differential Elimination of Anti-Thymocyte Globulin of Fresenius and Genzyme Impacts T-Cell Reconstitution After Hematopoietic Stem Cell Transplantation","volume":"10","author":"Oostenbrink","year":"2019","journal-title":"Front Immunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.148510","article-title":"Anti-Thymocyte Globulin as Graft-Versus-Host Disease Prevention in the Setting of Allogeneic Peripheral Blood Stem Cell Transplantation: A Review From the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation","volume":"102","author":"Baron","year":"2017","journal-title":"haematol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.803726\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T06:06:54Z","timestamp":1641276414000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.803726\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,4]]},"references-count":37,"alternative-id":["10.3389\/fimmu.2021.803726"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.803726","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2022,1,4]]},"article-number":"803726"}}