What are Aquaporins?
Aquaporins, also known as ‘water channels,’ are integral membrane proteins that conduct water molecules in and out of cells in the human body. Aquaporins from food sources are highly stable in food preparation and therefore may reach the gastrointestinal as intact proteins or peptides. In cases of breakdown in immunological tolerance, aquaporins from foods may become antigenic, and the immune reaction against them could result in antibody production. Aquaporins from food sources show similarity to human aquaporin, and thus they have high potential for triggering autoimmunity to nervous system tissues.
List of Aquaporins:
Amino acid sequence similarities occur between human aquaporin and plant aquaporins from soy, corn, spinach and tomato, which explains the cross-reactive antibodies produced in some patients.
Aquaporin also cross-reacts with legume serine proteinase inhibitors (serpins) found in beans, lentils, peas, peanuts, lupin, alfalfa, and clover. This may cause immune reactivity and the formation of cross-reactive antibodies. If these antibodies cross the blood-brain barrier (BBB) in susceptible individuals, it can result in neuromyelitis optica (NMO), a form of MS. These are severe neuroautoimmune disorders that affect the gray and white matter in the brain and spinal cord, causing demyelination, axonal damage and necrosis, ultimately resulting in paralysis and sensory loss. Seventy-five percent of NMO cases are associated with IgG1 antibody development that binds selectively to aquaporin-4 (AQP4), which is expressed in the astrocytic foot processes around the BBB. This can be of clinical importance for adjusting the diet in people with demyelinating disorders such as MS and NMO and/or those with a family history of such disorders.
Lambert, J., Mejia, S. & Vojdani, A. Plant and human aquaporins: pathogenesis from gut to brain. Immunol Res 67, 12–20 (2019). https://doi.org/10.1007/s12026-018-9046-z
Antibodies against plant aquaporins can trigger a cascade of immune reactivity that can lead to neuropyelitis optica.
Corn, soybean, spinach leaf, and tomato aquaporins have been shown to share homology with human aquaporin-4, which is abundantly expressed by brain astrocytic endfeet. Thus, antibodies formed against the dietary aquaporins may potentially cross-react with brain aquaporin, leading to blood-brain barrier permeability and setting the stage for neuroautoimmunity and neurodegeneration.
Of the four food aquaporins, spinach is the most common reactive. People with antibody reactivity to dietary aquaporins may consider abstaining from the aquaporin-containing food in order to prevent neurological tissue damage.
Follow up with blood brain barrier permeability and neurological tissue autoimmune reactivity testing.
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