TY - JOUR
T1 - Long-Term effect of hematopoietic cell transplantation on systemic inflammation in patients with mucopolysaccharidoses
AU - Van Den Broek, Brigitte T.A.
AU - Lindemans, Caroline A.
AU - Boelens, Jaap Jan
AU - Delemarre, Eveline M.
AU - Drylewicz, Julia
AU - Verhoeven-Duif, Nanda
AU - Van Hasselt, Peter M.
AU - Nierkens, Stefan
N1 - Publisher Copyright:
© 2021 American Society of Hematology. All rights reserved.
PY - 2021/8/24
Y1 - 2021/8/24
N2 - 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 5 66) of patients with MPS (n 5 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 5 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 follow-up, only 5 markers (receptor activator of nuclear factor kappa-B 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.
AB - 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 5 66) of patients with MPS (n 5 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 5 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 follow-up, only 5 markers (receptor activator of nuclear factor kappa-B 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.
UR - http://www.scopus.com/inward/record.url?scp=85113931110&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2020003824
DO - 10.1182/bloodadvances.2020003824
M3 - Article
AN - SCOPUS:85113931110
SN - 2473-9529
VL - 5
SP - 3092
EP - 3101
JO - Blood Advances
JF - Blood Advances
IS - 16
ER -