Journal of Inherited Metabolic Disease

, Volume 37, Issue 1, pp 1–12 | Cite as

Mucopolysaccharide diseases: A complex interplay between neuroinflammation, microglial activation and adaptive immunity

  • Louise D. Archer
  • Kia J. Langford-Smith
  • Brian W. Bigger
  • James E. Fildes


Mucopolysaccharide (MPS) diseases are lysosomal storage disorders (LSDs) caused by deficiencies in enzymes required for glycosaminoglycan (GAG) catabolism. Mucopolysaccharidosis I (MPS I), MPS IIIA, MPS IIIB and MPS VII are deficient in the enzymes α–L-Iduronidase, Heparan-N-Sulphatase, N-Acetylglucosaminidase and Beta-Glucuronidase, respectively. Enzyme deficiency leads to the progressive multi-systemic build-up of heparan sulphate (HS) and dermatan sulphate (DS) within cellular lysosomes, followed by cell, tissue and organ damage and in particular neurodegeneration. Clinical manifestations of MPS are well established; however as lysosomes represent vital components of immune cells, it follows that lysosomal accumulation of GAGs could affect diverse immune functions and therefore influence disease pathogenesis. Theoretically, MPS neurodegeneration and GAGs could be substantiating a threat of danger and damage to alert the immune system for cellular clearance, which due to the progressive nature of MPS storage would propagate disease pathogenesis. Innate immunity appears to have a key role in MPS; however the extent of adaptive immune involvement remains to be elucidated. The current literature suggests a complex interplay between neuroinflammation, microglial activation and adaptive immunity in MPS disease.


Dendritic Cell Heparan Sulphate Microglial Activation Migration Inhibitory Factor iNKT Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Conflict of interest



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Copyright information

© SSIEM and Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Louise D. Archer
    • 1
  • Kia J. Langford-Smith
    • 2
  • Brian W. Bigger
    • 2
  • James E. Fildes
    • 1
    • 3
  1. 1.The Transplant Centre, UHSMUniversity of ManchesterManchesterUK
  2. 2.Stem Cell & Neurotherapies LaboratoryUniversity of ManchesterManchesterUK
  3. 3.The Manchester Collaborative Centre for Inflammation Research (MCCIR)University of South ManchesterManchesterUK

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