{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T20:11:36Z","timestamp":1772741496702,"version":"3.50.1"},"reference-count":37,"publisher":"American Society of Hematology","issue":"16","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,8,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Mucopolysaccharidoses (MPS) are devastating inherited diseases treated with hematopoietic cell transplantation (HCT). However, disease progression, especially skeletal, still occurs in all patients. Secondary inflammation has been hypothesized to be a cause. To investigate whether systemic inflammation is present in untreated patients and to evaluate the effect of HCT on systemic inflammation, dried blood spots (n = 66) of patients with MPS (n = 33) treated with HCT between 2003 and 2019 were included. Time points consisted of pre-HCT and, for patients with MPS type I (MPS I), also at 1, 3, and 10 years of follow-up. Ninety-two markers of the OLINK inflammation panel were measured and compared with those of age-matched control subjects (n = 31) by using principal component analysis and Wilcoxon rank sum tests with correction. Median age at transplantation was 1.3 years (range, 0.2-4.8 years), and median time of pre-HCT sample to transplantation was 0.1 year. Normal leukocyte enzyme activity levels were achieved in 93% of patients post-HCT. Pretransplant samples showed clear separation of patients and control subjects. Markers that differentiated pre-HCT between control subjects and patients were mainly pro-inflammatory (50%) or related to bone homeostasis and extracellular matrix degradation (33%). After 10 years\u2019 follow-up, only 5 markers (receptor activator of nuclear factor kappa-\u0392 ligand, osteoprotegerin, axis inhibition protein 1 [AXIN1], stem cell factor, and Fms-related tyrosine kinase 3 ligand) remained significantly increased, with a large fold change difference between patients with MPS I and control subjects. In conclusion, systemic inflammation is present in untreated MPS patients and is reduced upon treatment with HCT. Markers related to bone homeostasis remain elevated up to 10 years after HCT and possibly reflect the ongoing skeletal disease, making them potential biomarkers for the evaluation of new therapies.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020003824","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T15:48:47Z","timestamp":1629215327000},"page":"3092-3101","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":8,"title":["Long-term effect of hematopoietic cell transplantation on systemic inflammation in patients with mucopolysaccharidoses"],"prefix":"10.1182","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3208-0685","authenticated-orcid":false,"given":"Brigitte T.A.","family":"van den Broek","sequence":"first","affiliation":[{"name":"Sylvia Toth Center for Multidisciplinary Follow up after Hematopoietic Cell Transplantation,"},{"name":"Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline A.","family":"Lindemans","sequence":"additional","affiliation":[{"name":"Princess Maxima Center and University Medical Center Utrecht, The Netherlands;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2232-6952","authenticated-orcid":false,"given":"Jaap Jan","family":"Boelens","sequence":"additional","affiliation":[{"name":"Stem Cell Transplantation and Cellular Therapies, MSK Kids, Memorial Sloan-Kettering Cancer Center, New York, NY;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eveline M.","family":"Delemarre","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Drylewicz","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nanda","family":"Verhoeven-Duif","sequence":"additional","affiliation":[{"name":"Section Metabolic Diagnostics, Department of Genetics, University Medical Centre Utrecht, Utrecht University, The Netherlands; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter M.","family":"van Hasselt","sequence":"additional","affiliation":[{"name":"Sylvia Toth Center for Multidisciplinary Follow up after Hematopoietic Cell Transplantation,"},{"name":"Section of Metabolic Diseases, Department of Child Health, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3406-817X","authenticated-orcid":false,"given":"Stefan","family":"Nierkens","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;"},{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","published-online":{"date-parts":[[2021,8,17]]},"reference":[{"key":"2021081715341785100_B1","doi-asserted-by":"crossref","first-page":"v4","DOI":"10.1093\/rheumatology\/ker394","article-title":"Overview of the mucopolysaccharidoses","volume":"50","author":"Muenzer","year":"2011","journal-title":"Rheumatology (Oxford)."},{"issue":"6","key":"2021081715341785100_B2","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/j.bbmt.2015.02.011","article-title":"Hematopoietic cell transplantation for mucopolysaccharidosis patients is safe and effective: results after implementation of international guidelines","volume":"21","author":"Aldenhoven","year":"2015","journal-title":"Biol Blood Marrow Transplant."},{"issue":"19","key":"2021081715341785100_B3","doi-asserted-by":"crossref","first-page":"3981","DOI":"10.1182\/blood-2012-09-455238","article-title":"Outcomes of transplantation using various hematopoietic cell sources in children with Hurler syndrome after myeloablative conditioning","volume":"121","author":"Boelens","year":"2013","journal-title":"Blood."},{"issue":"13","key":"2021081715341785100_B4","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.1182\/blood-2014-11-608075","article-title":"Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study","volume":"125","author":"Aldenhoven","year":"2015","journal-title":"Blood."},{"issue":"5","key":"2021081715341785100_B5","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.bbmt.2019.11.025","article-title":"Longitudinal analysis of ocular disease in children with mucopolysaccharidosis I after hematopoietic cell transplantation","volume":"26","author":"van den Broek","year":"2020","journal-title":"Biol Blood Marrow Transplant."},{"issue":"5","key":"2021081715341785100_B6","doi-asserted-by":"crossref","first-page":"386","DOI":"10.2106\/JBJS.O.00601","article-title":"Progression of hip dysplasia in mucopolysaccharidosis type I Hurler after successful hematopoietic stem cell transplantation","volume":"98","author":"Langereis","year":"2016","journal-title":"J Bone Joint Surg Am."},{"issue":"5","key":"2021081715341785100_B7","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1111\/aos.13627","article-title":"The effect of haemopoietic stem cell transplantation on the ocular phenotype in mucopolysaccharidosis type I (Hurler)","volume":"96","author":"Javed","year":"2018","journal-title":"Acta Ophthalmol."},{"issue":"9","key":"2021081715341785100_B8","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1038\/labinvest.3780345","article-title":"Articular chondrocytes from animals with a dermatan sulfate storage disease undergo a high rate of apoptosis and release nitric oxide and inflammatory cytokines: a possible mechanism underlying degenerative joint disease in the mucopolysaccharidoses","volume":"81","author":"Simonaro","year":"2001","journal-title":"Lab Invest."},{"issue":"3","key":"2021081715341785100_B9","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1002\/jnr.21134","article-title":"Cytokines, neurotrophins, and oxidative stress in brain disease from mucopolysaccharidosis IIIB","volume":"85","author":"Villani","year":"2007","journal-title":"J Neurosci Res."},{"issue":"12","key":"2021081715341785100_B10","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1016\/j.joca.2013.08.001","article-title":"Osteoimmunology in mucopolysaccharidoses type I, II, VI and VII. 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