90 research outputs found
HLA-identical umbilical cord blood transplantation from a sibling donor in juvenile myelomonocytic leukemia.
No full textThe Wiskott-Aldrich syndrome protein is required for iNKT cell maturation and function
No full textThe Wiskott-Aldrich syndrome (WAS) protein (WASp) is a regulator of actin cytoskeleton in hematopoietic cells. Mutations of the WASp gene cause WAS. Although WASp is involved in various immune cell functions, its role in invariant natural killer T (iNKT) cells has never been investigated. Defects of iNKT cells could indeed contribute to several WAS features, such as recurrent infections and high tumor incidence. We found a profound reduction of circulating iNKT cells in WAS patients, directly correlating with the severity of clinical phenotype. To better characterize iNKT cell defect in the absence of WASp, we analyzed was(-/-) mice. iNKT cell numbers were significantly reduced in the thymus and periphery of was(-/-) mice as compared with wild-type controls. Moreover analysis of was(-/-) iNKT cell maturation revealed a complete arrest at the CD44(+) NK1.1(-) intermediate stage. Notably, generation of BM chimeras demonstrated a was(-/-) iNKT cell-autonomous developmental defect. was(-/-) iNKT cells were also functionally impaired, as suggested by the reduced secretion of interleukin 4 and interferon gamma upon in vivo activation. Altogether, these results demonstrate the relevance of WASp in integrating signals critical for development and functional differentiation of iNKT cells and suggest that defects in these cells may play a role in WAS pathology
Outcome of Non-hematological Autoimmunity After Hematopoietic Cell Transplantation in Children with Primary Immunodeficiency
No full textPurpose: Knowledge of post-hematopoietic cell transplantation (HCT) non-hematological autoimmune disease (AD) is far from satisfactory.
Method: This multicenter retrospective study focuses on incidence, risk factors, and outcomes of post-HCT AD in 596 children with primary immunodeficiency (PID) who were transplanted from 2009 to 2018.
Results: The indications of HCT were severe combined immunodeficiency (SCID, n = 158, 27%) and non-SCID PID (n = 438, 73%). The median age at HCT was 2.3 years (range, 0.04 to 18.3 years). The 5-year overall survival for the entire cohort was 79% (95% cumulative incidence (CIN), 74-83%). The median follow-up of surviving patients was 4.3 years (0.08 to 14.7 years). The CIN of post-HCT AD was 3% (2-5%) at 1 year post-HCT, 7% (5-11%) at 5 years post-HCT, and 11% (7-17%) at 8 years post-HCT. The median onset of post-HCT AD was 2.2 years (0.12 to 9.6 years). Autoimmune thyroid disorder (n = 19, 62%) was the most common post-HCT AD, followed by neuromuscular disorders (n = 7, 22%) and rheumatological manifestations (n = 5, 16%). All patients but one required treatment for post-HCT AD. After multivariate analysis, age at transplant (p = 0.01) and T cell-depleted graft (p < 0.001) were significant predictors of post-HCT AD. None of the T cell-depleted graft recipients developed post-HCT AD. Patients with a lower CD3+ count at 6 months post-HCT had a significant higher incidence of post-HCT AD compared to disease controls. Graft-versus-host disease, viral infection, and donor chimerism had no association with post-HCT AD.
Conclusion: Post-HCT AD occurred in 11% at 8 years post-HCT and its occurrence was associated with older age at HCT and unmanipulated graft
HLA-identical umbilical cord blood transplantation from a sibling donor in juvenile myelomonocytic leukemia
No full textN/
Pharmacokinetics of rituximab in a pediatric patient with therapy-resistant nephrotic syndrome
No full textDeterminants of the relationship between cytokine production in pregnant women and their infants.
No full textExposure to environmental factors during fetal life and infancy is thought to play an important role in the early development of innate and adaptive immunity. The immunological relationship between mother and infant and the effect that environmental exposures have during pregnancy and early childhood have not been studied extensively. Here the production of cytokines was measured in 146 pairs of mothers and their 2- month-old infants. The effect of place of residence, socio-economic variables, parasitic infections as well as maternal and child characteristics on measured cytokine production was determined. Mothers producing high levels of IL-10, IFN-gamma and IL-5 were more likely to have infants who also produced high levels of these cytokines either spontaneously (OR 2.6(95%CI 1.2-5.4), OR 2.9(CI 1.3-6.6), OR 11.2(CI 4.6-27.2), respectively) or in response to PHA (IL-10: OR 3.0(CI 1.4-6.6), IFN-gamma: OR 2.0(CI 1.0-4.2), respectively) even after adjustment for potential confounding variables. This was not the case for TNF-alpha. In response to LPS, place of residence was a strong determinant of infant IL-10 (OR 0.2(CI 0.1-0.9)) and TNF-alpha (OR 0.3(CI 0.1-0.9)) production. Maternal protozoan infections was independently associated with reduced infant IL10 in response to PHA and to LPS as well as reduced TNF-alpha and IFN-gamma in response to PHA. These results indicate strong relationship between maternal and infant's cellular immune responses even after taking into account many environmental influences that could affect infant's response directly or indirectly through uterine microenvironment. However, place of residence and intestinal infections may still directly affect the immune responses of the infant. Taken together, the study provides evidence for imprinted cytokine responses of an infant which may have implications for their reaction to incoming antigens, warranting further investigation into the role that genetics or epigenetics play in shaping the cytokine response by an infant to self or external antigens
First Successful Allogeneic Hematopoietic Stem Cell Transplantation for MKL1 Deficiency
No full textTransplantation and immunomodulatio
Characteristics of the BMT recipients and donors.
No full text<p>Abbreviations: ALL = acute lymphoblastic leukemia; AML = acute myeloid leukemia; CR = complete remission; F = female; JMML = juvenile myelo-monocytic leukemia; M = male; NHL = non- Hodgkin lymphoma.</p>a<p>According to the treatment protocols of the Dutch Childhood Leukemia Study Group.</p><p>Characteristics of the BMT recipients and donors.</p
Child and parental adaptation to pediatric stem cell transplantation
No full textAllogeneic pediatric stem cell transplantation (SCT) is a very intensive treatment with a high mortality and morbidity. The objectives of this study were to assess the (1) self- and proxy-reported health-related quality of life (HRQoL) compared to a norm group, (2) levels of parenting stress compared to a norm group, (3) differences in HRQoL and parenting stress pre- and post-SCT, and (4) effect of child age and parenting stress on self- and proxy-reported HRQoL pre- and post-SCT. Pre- and on average 10 months post-SCT, 21 children and adolescents and their parent(s) completed questionnaires on HRQoL and the mothers completed a measure of parenting stress. Post-SCT, home functioning, physical functioning, and total HRQoL scores were lower than the norm group. We found stable HRQoL scores over time with the exception of the domain home functioning, which was rated lower post-SCT than pre-SCT. Parents reported lower HRQoL scores than the children pre- and post-SCT and younger children experienced better HRQoL than older children. Parenting stress was higher post-SCT than pre-SCT and high levels of parenting stress were predictive of poor parental ratings of child HRQoL post-SCT. Ongoing psychosocial assessment post-SCT is necessary to target children with a lowered HRQoL and parents who experience elevated parenting stress who may be in greater need of more supportive car
Overview of 15-year severe combined immunodeficiency in the Netherlands: towards newborn blood spot screening
No full textSevere combined immune deficiency (SCID) is a fatal primary immunodeficiency usually presenting in the first months of life with (opportunistic) infections, diarrhea, and failure to thrive. Hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are curative treatment options. The objective of the study was to assess the morbidity, mortality, and diagnostic and therapeutic delay in children with SCID in the Netherlands in the last 15 years. These data may help to judge whether SCID should be considered to be included in our national neonatal screening program. In the period 1998-2013, 43 SCID patients were diagnosed in the Netherlands, 11 of whom were atypical SCID (presentation beyond the first year). The median interval between the first symptom and diagnosis was 2 months (range 0-1173 months). The total mortality was 42 %. In total, 32 patients were treated with HSCT of whom 8 were deceased. Nine patients died due to severe infectious complications before curative treatment could be initiated. Conclusion: Because of a high mortality of patients with SCID before HSCT could be initiated, only a national newborn screening program and pre-emptive HSCT or GT will be able to improve survival of these patients
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