Water-clogging antibodies
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《实验药学杂志》
Antibodies from patients with neuromyelitis optica bind to the water channel aquaporin-4 (yellow) in brain tissue.
Autoantibodies produced during a severe variant of multiple sclerosis (MS) latch on to water channels in the brain, according to Lennon and colleagues on page 473.
Optic–spinal MS (or neuromyelitis optica, NMO) is a severe demyelinating disease that affects the spinal cord and optic nerves and is often misdiagnosed as classical MS, despite the absence of typical MS-like brain lesions. This group recently described an antibody that was present in the serum of up to 70% of patients with NMO, but was never found in patients with classical MS. The antibody bound to an unidentified antigen prominent at the blood–brain barrier.
Lennon and her colleagues now identify the target of the antibody as the water channel aquaporin-4 (AQP4). AQP4 is the most abundant water channel in the brain and is concentrated in the astrocyte membranes that border the blood–brain barrier. The expression of this protein is increased in patients with epilepsy and certain brain tumors, probably accounting for the associated brain edema that can limit blood flow and deprive the brain of oxygen.
Lennon suspects that the consequences of the antibody's binding to AQP4 in the brain are twofold. The binding might directly alter the function of the water channel, triggering swelling. The antibodies might also trigger complement activation, which could then initiate the robust inflammatory reaction that is characteristic of early NMO.
Aquaporins are also abundant in the kidney, where they are required for normal water retention and urine concentration. Indeed, the anti-AQP4 antibodies from the NMO patients reacted with kidney tissue. It remains a mystery why these patients do not develop renal abnormalities.
The authors now plan to test whether AQP4-specific antibodies can trigger an NMO-like disease in mice. In the meantime, they have shown that these antibodies provide a useful diagnostic tool to distinguish NMO patients from those with conventional MS, as the diseases call for distinct treatment strategies.(Heather L. Van Epps)
Autoantibodies produced during a severe variant of multiple sclerosis (MS) latch on to water channels in the brain, according to Lennon and colleagues on page 473.
Optic–spinal MS (or neuromyelitis optica, NMO) is a severe demyelinating disease that affects the spinal cord and optic nerves and is often misdiagnosed as classical MS, despite the absence of typical MS-like brain lesions. This group recently described an antibody that was present in the serum of up to 70% of patients with NMO, but was never found in patients with classical MS. The antibody bound to an unidentified antigen prominent at the blood–brain barrier.
Lennon and her colleagues now identify the target of the antibody as the water channel aquaporin-4 (AQP4). AQP4 is the most abundant water channel in the brain and is concentrated in the astrocyte membranes that border the blood–brain barrier. The expression of this protein is increased in patients with epilepsy and certain brain tumors, probably accounting for the associated brain edema that can limit blood flow and deprive the brain of oxygen.
Lennon suspects that the consequences of the antibody's binding to AQP4 in the brain are twofold. The binding might directly alter the function of the water channel, triggering swelling. The antibodies might also trigger complement activation, which could then initiate the robust inflammatory reaction that is characteristic of early NMO.
Aquaporins are also abundant in the kidney, where they are required for normal water retention and urine concentration. Indeed, the anti-AQP4 antibodies from the NMO patients reacted with kidney tissue. It remains a mystery why these patients do not develop renal abnormalities.
The authors now plan to test whether AQP4-specific antibodies can trigger an NMO-like disease in mice. In the meantime, they have shown that these antibodies provide a useful diagnostic tool to distinguish NMO patients from those with conventional MS, as the diseases call for distinct treatment strategies.(Heather L. Van Epps)