title: Long-Term Stable Mixed Chimerism after Hematopoietic Stem Cell Transplantation in Patients with Non-Malignant Disease, Shall We Be Tolerant?
abstract: Long-term stable mixed chimerism is a rare and poorly understood phenomenon post hematopoietic stem cell transplantation. This study aims to shed light on whether the two hematopoietic systems in patients with mixed chimerism remain functional. Additionally, we investigate possible immunologic differences in these individuals compared to patients with only donor derived immune cells. Patients with donor and mixed chimerism, at median 10 (5-16) years post-HSCT for non-malignant diseases, were assessed regarding clinical situation and immune system (phenotypical and functional). No difference in long-term outcome was seen in terms of general wellbeing, central phenotypic immune system features (e.g., differentiation status, CD4/CD8 ratio, B and NK-cell frequency) and antibody responses to immunizations. At a median of 10 years post transplantation, patients with mixed chimerism had significantly higher IgG3 and platelet levels. Additionally, these patients had higher NKT-cell levels (CD94+CD8+ and CD56+CD8+) than patients with donor chimerism. In depth phenotypic analysis of patients with mixed chimerism demonstrated recipient-derived fractions in most immune cell lineages (e.g., T-cell, B-cell and NK-cell subsets). Recipient cells were also capable of responding to mitogenic stimulation with production of several cytokines. In conclusion, long-term mixed chimerism did not negatively affect patient wellbeing and long-term outcome. Moreover, recipient-derived immunity may still be functional in these patients, suggesting an active state of tolerance and immunologic dependence on both hematopoietic systems.
authors.affiliation: Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.|Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Arwen
authors.initials: A
authors.lastname: Stikvoort
authors.affiliation: Division of Paediatrics, Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden.|Hematology/Immunology/HSCT Section, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Sundin
authors.affiliation: Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Uzunel
authors.affiliation: Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Gertow
authors.affiliation: Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.|Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Berit
authors.initials: B
authors.lastname: Sundberg
authors.affiliation: Department of clinical immunology and transfusion medicine, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Schaffer
authors.affiliation: Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.|Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Mattsson
authors.affiliation: Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.|Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, Sweden.|Department of clinical immunology and transfusion medicine, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Uhlin
mesh_terms: D046528:Chimerism; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans