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. 2019 Feb 5:19:100455.
doi: 10.1016/j.ymgmr.2019.100455. eCollection 2019 Jun.

Biomarkers in patients with mucopolysaccharidosis type II and IV

Honoka Fujitsuka  1   2 , Kazuki Sawamoto  1 , Hira Peracha  1   3 , Robert W Mason  1   3 , William Mackenzie  1 , Hironori Kobayashi  4 , Seiji Yamaguchi  4 , Yasuyuki Suzuki  2 , Kenji Orii  5 , Tadao Orii  5 , Toshiyuki Fukao  5 , Shunji Tomatsu  1   4   5   6
Affiliations

Biomarkers in patients with mucopolysaccharidosis type II and IV

Honoka Fujitsuka et al. Mol Genet Metab Rep. .

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.

Keywords: Cytokines; Glycosaminoglycans; Hunter syndrome; Inflammation; Morquio syndrome.

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Figures

Fig. 1
Fig. 1
Blood levels of pro-inflammatory factors and collagen type II in patients with MPS and normal control. (a) EGF, (c) IL-1β, (e) IL-6, (g) TNF-α, (i) MIP-1α, (k) MMP-1, (m) MMP-2, (o) MMP-9 and (q) Collagen type II levels in patients with MPS II. (b) EGF, (d) IL-1β, (f) IL-6, (h) TNF-α, (j) MIP-1α, (l) MMP-1, (n) MMP-2, (p) MMP-9 and (r) Collagen type II levels in patients with MPS IV. *p < .05 vs normal control group. #p < .05 vs MPS IVA untreated patients.
Fig. 1
Fig. 1
Blood levels of pro-inflammatory factors and collagen type II in patients with MPS and normal control. (a) EGF, (c) IL-1β, (e) IL-6, (g) TNF-α, (i) MIP-1α, (k) MMP-1, (m) MMP-2, (o) MMP-9 and (q) Collagen type II levels in patients with MPS II. (b) EGF, (d) IL-1β, (f) IL-6, (h) TNF-α, (j) MIP-1α, (l) MMP-1, (n) MMP-2, (p) MMP-9 and (r) Collagen type II levels in patients with MPS IV. *p < .05 vs normal control group. #p < .05 vs MPS IVA untreated patients.
Fig. 1
Fig. 1
Blood levels of pro-inflammatory factors and collagen type II in patients with MPS and normal control. (a) EGF, (c) IL-1β, (e) IL-6, (g) TNF-α, (i) MIP-1α, (k) MMP-1, (m) MMP-2, (o) MMP-9 and (q) Collagen type II levels in patients with MPS II. (b) EGF, (d) IL-1β, (f) IL-6, (h) TNF-α, (j) MIP-1α, (l) MMP-1, (n) MMP-2, (p) MMP-9 and (r) Collagen type II levels in patients with MPS IV. *p < .05 vs normal control group. #p < .05 vs MPS IVA untreated patients.
Fig. 2
Fig. 2
Blood GAGs levels in patients with MPS and normal control. (a) HS0S, HSNS, and DS levels in patients with MPS II, (b) HS0S, HSNS, and DS levels in patients with MPS IV, (c) KS levels in patients with MPS II, (d) KS levels in patients with MPS IV. *p < .05 vs normal control group. #p < .05 vs MPS II untreated patients.
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