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

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  • Published:
Journal of Inherited Metabolic Disease

Abstract

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.

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Authors and Affiliations

  1. The Transplant Centre, UHSM, University of Manchester, Manchester, England, UK

    Louise D. Archer & James E. Fildes

  2. Stem Cell & Neurotherapies Laboratory, University of Manchester, Manchester, England, UK

    Kia J. Langford-Smith & Brian W. Bigger

  3. The Manchester Collaborative Centre for Inflammation Research (MCCIR), University of South Manchester, Manchester, M13 9PL, England, UK

    James E. Fildes

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  1. Louise D. Archer
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  2. Kia J. Langford-Smith
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  3. Brian W. Bigger
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  4. James E. Fildes
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Correspondence to James E. Fildes.

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Communicated by: Douglas A. Brooks

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Archer, L.D., Langford-Smith, K.J., Bigger, B.W. et al. Mucopolysaccharide diseases: A complex interplay between neuroinflammation, microglial activation and adaptive immunity. J Inherit Metab Dis 37, 1–12 (2014). https://doi.org/10.1007/s10545-013-9613-3

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