Invited critical reviewAquaporins, anti-aquaporin-4 autoantibodies and neuromyelitis optica
Highlights
► Aquaporins are protein channels that allow the movement of water and other molecules. ► Aquaporin-4 is the target of an autoimmune response in neuromyelitis optica. ► Anti-AQP4 autoantibodies have diagnostic usefulness with reasonable sensitivity and high specificity. ► Anti-AQP4 can be measured, although there is no standard method.
Introduction
The diffusion of water across biological membranes has long been known. It occurs across all lipid bilayers and is a slow and low-capacity bidirectional process. However, many physiological processes require rapid movement of water. More than 30 years ago, it was considered that in certain specialized epithelia (renal tubules, red cells, secretory glands) there should be an additional system for the rapid movement of large masses of water. This system would possess high capacity for water and be specific, not allowing the passage of other substances, such as hydronium ions (H3O+). Water would move according to the saline osmotic gradient and the system could be modified or inhibited by various substances. The evidence pointed to the notion that it might be a membrane channel for water.
Section snippets
Membrane channels for water
In 1988, in studies addressing Rh cell antigens, a 28 kDa protein shared by red cells from different species that participated in the movement of water across biological membranes was found unexpectedly [1]. Later, coding DNA was isolated and a membrane polypeptide with several transmembrane domains with repeated amino acid sequences in the amino and carboxyl ends were identified. Its structure suggested that it might be part of a channel and that it could correspond to a component of water
The aquaporin family of proteins
Aquaporin-1 (AQP1) was the first aquaporin described in humans. Currently, for aquaporins at least 13 physiological sequences have been described (Table 1), which can be divided into two broad groups. On one hand, there are the channels that transport water exclusively, and on the other there are the aquaglyceroporins, which transport water and glycerol. A third group of aquaporins called super-AQP, with less homology with the above, has been proposed.
Clinical applications of aquaporin measurements
The current and potential usefulness of aquaporin measurements can be divided into two major diagnostic and therapeutic areas.
Neuromyelitis optica
Neuromyelitis optica (NMO), also known as Devic's disease, is a severe immune-mediated demyelinating and necrotizing disease that predominantly affects the optic nerves and spinal cord. It has been considered a form of multiple sclerosis in which inflammatory lesions are restricted to the optic nerve and spinal cord, but currently it is considered a distinct clinical entity. NMO causes acute eye pain with loss of function and myelitis with symmetric paraplegia, sensory loss, and sphincter
Anti-AQP4 antibodies
In 2004, Lennon et al. found anti-AQP4 antibodies in the serum of individuals with NMO and related disorders, but not in the serum of subjects with multiple sclerosis and normal individuals. Therefore, these antibodies are also called anti-NMO [120]. Anti-AQP4 antibodies are directed against epitopes located in extracellular loops of AQP4 (Fig. 2) [121]. Specifically, anti-AQP4 antibodies recognize an epitope located in the E outer loop of AQP4, which is considered the major epitope of
Anti-AQP4 assays
At least 15 methods for assaying anti-AQP4 antibodies have been reported. The sensitivity varies widely between 33 and 91% (median 63%), while the overall specificity remains high (85% to 100% with a median of 99%) [119]. Methods depending on the substrate can be divided into indirect immunofluorescence or immunohistochemistry using tissue sections as substrate. Sensitivity is variable (38–87%); the methods are semiquantitative (titres) and depend on the observer's experience. These methods can
Conclusion
AQPs are a family of protein channels that allow the movement of water, gas, glycerol and other molecules. AQP4 is the one that has gained the greatest clinical relevance; it is abundantly expressed in the brain, where it regulates the movement of water into and out of it, and it is the target of an autoimmune response in NMO and other related syndromes. NMO is a rare disease that is difficult to diagnose and has atypical partially clinical forms. Differential diagnostic problems with multiple
References (155)
- et al.
Identification, purification, and partial characterization of a novel Mr 28,000 integral membrane protein from erythrocytes and renal tubules
J Biol Chem
(1988) - et al.
Erythrocyte Mr 28,000 transmembrane protein exists as a multisubunit oligomer similar to channel proteins
J Biol Chem
(1991) - et al.
Aquaporin tetramer composition modifies the function of tobacco aquaporins
J Biol Chem
(2010) - et al.
Aquaporins in tumor growth and angiogenesis
Cancer Lett
(2010) Regulation of brain aquaporins
Neurochem Int
(2010)- et al.
Expression of aquaporin water channels in mouse spinal cord
Neuroscience
(2004) - et al.
Aquaporin-4 contributes to the resolution of peritumoral brain oedema in human glioblastoma multiforme after combined chemotherapy and radiotherapy
Eur J Cancer
(2009) - et al.
Aquaporin-4 expression is increased in edematous meningiomas
J Clin Neurosci
(2009) - et al.
Functions of aquaporins in the eye
Prog Retin Eye Res
(2008) - et al.
Involvement of aquaporin-1 in gastric epithelial cell migration during wound repair
Biochem Biophys Res Commun
(2009)
Defective secretion of saliva in transgenic mice lacking aquaporin-5 water channels
J Biol Chem
Abnormal distribution of aquaporin-5 water channel protein in salivary glands from Sjögren's syndrome patients
Lab Invest
Defective cellular trafficking of lacrimal gland aquaporin-5 in Sjögren's syndrome
Lancet
Specific aquaporins facilitate the diffusion of hydrogen peroxide across membranes
J Biol Chem
Intact AQP0 performs cell-to-cell adhesion
Biochem Biophys Res Commun
The common modification in α-crystallin in the lens, N101D, is associated with increased opacity in a mouse mode
J Biol Chem
Impaired stratum corneum hydration in mice lacking epidermal water channel aquaporin-3
J Biol Chem
Fast and selective ammonia transport by aquaporin-8
J Biol Chem
Functional characterization of a human aquaporin 0 mutation that leads to a congenital dominant lens cataract
Exp Eye Res
Gene expression of paired abdominal adipose AQP7 and liver AQP9 in patients with morbid obesity: relationship with glucose abnormalities
Metabolism
Role of aquaporins in cell migration and edema formation in human brain tumors
Exp Cell Res
Cerebrospinal fluid findings in aquaporin-4 antibody positive neuromyelitis óptica: results from 211 lumbar punctures
J Neurol Sci
Association of anti-aquaporin-4 antibody positive neuromyelitis optica with myasthenia gravis
J Neurol Sci
Prominent brainstem symptoms/signs in patients with neuromyelitis optica in a Taiwanese population
J Clin Neurosci
HLA-DPB1 0501 is associated with susceptibility to anti-aquaporin-4 antibodies positive neuromyelitis optica in southern Han Chinese
J Neuroimmunol
Isolation of the cDNA for erythrocyte integral membrane protein of 28 kilodaltons: member of an ancient channel family
Proc Natl Acad Sci U S A
Aquaporin CHIP: the archetypal molecular water channel
Am J Physiol
Aquaporin-1 water channels in short and long loop descending thin limbs and in descending vasa recta in rat kidney
Am J Physiol
Decreased pulmonary vascular permeability in aquaporin-1-null humans
Proc Natl Acad Sci U S A
Reduced cerebrospinal fluid production and intracranial pressure in mice lacking choroid plexus water channel Aquaporin-1
FASEB J
The human gene for water channel aquaporin 1 (AQP1) is localized on chromosome 7p15–>p14
Cytogenet Cell Genet
Defective urinary-concentrating ability due to a complete deficiency of aquaporin-1
N Engl J Med
Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance
Proc Natl Acad Sci U S A
Aquaporin water channels: atomic structure molecular dynamics meet clinical medicine
J Clin Invest
Aquaporins as gas channels
Pflugers Arch
Acid–base transport by the renal proximal tubule
J Nephrol
Role of aquaporin 1 (AQP1) as a CO2 channel in chronic metabolic acidosis
FASEB J
Aquaporin-1 transports NO across cell membranes
Hypertension
Novel role of AQP-1 in NO dependent vasorelaxation
Am J Physiol Renal Physiol
Cellular and subcellular immunolocalization of vasopressin-regulated water channel in rat kidney
Proc Natl Acad Sci U S A
Cloning and expression of apical membrane water channel of rat kidney collecting tubule
Nature
Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke
Nat Med
Aquaporins: translating bench research to human disease
J Exp Biol
Aquaporins at a glance
J Cell Sci
Role of aquaporin-4 in cerebral edema and stroke
Handb Exp Pharmacol
Protective role of aquaporin-4 water channels after contusion spinal cord injury
Ann Neurol
Aquaporin-4 expression is increased in oedematous human brain tumours
J Neurol Neurosurg Psychiatry
Expression pattern of the water channel aquaporin-4 in human gliomas is associated with blood–brain barrier disturbance but not with patiens survival
J Neurosci Res
Impaired olfaction in mice lacking aquaporin-4 water channels
FASEB J
Skeletal muscle function and water permeability in aquaporin-4 deficient mice
Am J Physiol Cell Physiol
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Optic neuritis with radiological longitudinal spinal cord involvement and seronegative anti-aquaporin antibody: Evidence from a case study
2017, Multiple Sclerosis and Related DisordersCitation Excerpt :The discovery of the anti-aquaporin antibody shed light on the diseases known hereinafter as neuromyelitis optica spectrum disease (NMOSD) (González et al., 2013).
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2015, Journal of the Neurological SciencesCitation Excerpt :Kitazawa et al. reported a case of elderly-onset NMO, which developed after the diagnosis of prostate adenocarcinoma and relapsed after a 23-valent pneumococcal polysaccharide vaccination [102], suggesting that activation of the immune system by complement activation induced by vaccination could be involved in the onset and relapses of NMO [75]. AQP4-IgG binds with greater affinity to M23-AQP4 than to M1-AQP4, contributing to the bivalent binding of IgG [75]. Hinson and co-workers proposed that M1-AQP4 is rapidly internalized by astrocytes upon AQP4-IgG exposure, resulting in increased OAP size and enhanced CDC, whereas M23-AQP4 resists internalization [103].
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