[HTML][HTML] Biomarkers in patients with mucopolysaccharidosis type II and IV

H Fujitsuka, K Sawamoto, H Peracha… - Molecular genetics and …, 2019 - Elsevier
H Fujitsuka, K Sawamoto, H Peracha, RW Mason, W Mackenzie, H Kobayashi, S Yamaguchi…
Molecular genetics and metabolism reports, 2019Elsevier
Abstract Glycosaminoglycans (GAGs), dermatan sulfate (DS), heparan sulfate (HS), and
keratan sulfate (KS), are the primary biomarkers in patients with mucopolysaccharidoses
(MPS); however, little is known about other biomarkers. To explore potential biomarkers and
their correlation with GAGs, blood samples were collected from 46 MPS II patients, 34 MPS
IVA patients, and 5 MPS IVB patients. We evaluated the levels of 8 pro-inflammatory factors
(EGF, IL-1β, IL-6, MIP-1α, TNF-α, MMP-1, MMP-2, and MMP-9), collagen type II, and DS, HS …
Abstract
Glycosaminoglycans (GAGs), dermatan sulfate (DS), heparan sulfate (HS), and keratan sulfate (KS), are the primary biomarkers in patients with mucopolysaccharidoses (MPS); however, little is known about other biomarkers. To explore potential biomarkers and their correlation with GAGs, blood samples were collected from 46 MPS II patients, 34 MPS IVA patients, and 5 MPS IVB patients. We evaluated the levels of 8 pro-inflammatory factors (EGF, IL-1β, IL-6, MIP-1α, TNF-α, MMP-1, MMP-2, and MMP-9), collagen type II, and DS, HS (HS0S, HSNS), and KS (mono-sulfated, di-sulfated) in blood.
Eight biomarkers measured were significantly elevated in untreated MPS II patients, compared with those in normal controls: EGF, IL-1β, IL-6, HS0S, HSNS, DS, mono-sulfated KS, and di-sulfated KS. The same eight biomarkers remained elevated in ERT-treated patients. However, only three biomarkers remained elevated in post-HSCT MPS II patients: EGF, mono-sulfated KS, and di-sulfated KS. Post-HSCT patients with MPS II showed that IL-1β and IL-6 were normalized as HS and DS levels decreased. Eight biomarkers were significantly elevated in untreated MPS IVA patients: EGF, IL-1β, IL-6, MIP-1α, MMP-9, HSNS, mono-sulfated KS, and di-sulfated KS, and four biomarkers were elevated in MPS IVA patients under ERT: IL-6, TNF-α, mono-sulfated KS, and di-sulfated KS. There was no reduction of KS in the ERT-treated MPS IVA patient, compared with untreated patients. Two biomarkers were significantly elevated in untreated MPS IVB patients: IL-6 and TNF-α.
Reversely, collagen type II level was significantly decreased in untreated and ERT-treated MPS II patients and untreated MPS IVA patients.
In conclusion, selected pro-inflammatory factors can be potential biomarkers in patients with MPS II and IV as well as GAGs levels.
Elsevier