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Absence of aquaporin-4 expression in lesions of neuromyelitis optica but increased expression in multiple sclerosis lesions and normal-appearing white matter

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Abstract

Aquaporin-4 (AQP4) has recently been implicated in the pathogenesis of neuromyelitis optica (NMO) where it has been identified as the first defined autoantigen pertinent to an inflammatory demyelinating disorder of the human CNS. Furthermore, a recent case report has shown a lack of AQP4 expression in the spinal cord lesions of NMO. However, the pattern of AQP4 expression in multiple sclerosis (MS) tissues has not been well-defined. In the present investigation we have confirmed a lack of expression of AQP4 in optic and spinal cord lesions in NMO which contrasted sharply with the increased levels of AQP4 expression seen in MS lesions. Furthermore a detailed immunohistochemical and semi-quantitative analysis is used to describe the expression pattern of AQP4 on well-characterized tissue microarray samples of MS and control white matter. Anatomically AQP4 was more highly expressed in all categories of MS tissue compared to normal control tissues with the most abundant expression in active lesions. Within active lesions AQP4 expression was significantly correlated with expression of the pro-inflammatory cytokine osteopontin. At the cellular level dual-labeling immunofluoresence demonstrated that increased expression of AQP4 was most pronounced at the astrocytic endfeet but was also associated with the cell bodies of astrocytes in the tissue parenchyma. The finding of increased AQP4 expression in MS lesions in contrast to the lack of expression in NMO lesions may suggest different mechanisms of initiation and progression between the two disease states.

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Acknowledgements

The authors wish to thank MS Ireland for grant funding. We thank Mr. Gordon McGregor for his excellent technical assistance. We also are indebted to Dr Raeburn Forbes and Dr Rory Convery for neurological diagnosis of the NMO case.

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Authors and Affiliations

  1. Neuropathology Laboratory, Institute of Pathology, Royal Group of Hospitals Trust, Grosvenor Road, Belfast, N. Ireland, BT12 6BL, UK

    Colin Sinclair, Brian Herron & Stephen McQuaid

  2. Multiple Sclerosis and Inflammation Research Groups, School of Medicine and Dentistry, Institute of Pathology, Grosvenor Road, Belfast, N. Ireland, BT12 6BL, UK

    John Kirk

  3. National University of Ireland, Galway, Ireland, UK

    Una Fitzgerald

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  1. Colin Sinclair
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  2. John Kirk
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  5. Stephen McQuaid
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Correspondence to Stephen McQuaid.

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Sinclair, C., Kirk, J., Herron, B. et al. Absence of aquaporin-4 expression in lesions of neuromyelitis optica but increased expression in multiple sclerosis lesions and normal-appearing white matter. Acta Neuropathol 113, 187–194 (2007). https://doi.org/10.1007/s00401-006-0169-2

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  • DOI: https://doi.org/10.1007/s00401-006-0169-2

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