Aquaporin 4 molecular mimicry and implications for neuromyelitis optica

Abstract

Neuromyelitis Optica (NMO) is associated with antibodies to aquaporin 4 (AQP4). We hypothesized that antibodies to AQP4 can be triggered by exposure to environmental proteins. We compared human AQP4 to plant and bacterial proteins to investigate the occurrence of significantly similar structures and sequences. High similarity to a known epitope for NMO-IgG, AQP4(207-232), was observed for corn ZmTIP4-1. NMO and non-NMO serum was assessed for reactivity to AQP4(207-232) and the corn peptide. NMO patient serum showed reactivity to both peptides as well as to plant tissue. These findings warrant further investigation into the role of the environment in NMO etiology.

Detection of antibodies against human and plant aquaporins in patients with multiple sclerosis

“…This peptide was not used in either the Vaishnav et al study [28] or this present study. Using antibody bound to live M1 and M23 cells, Iorio's group found that while NMO serum bound to 100% of the AQP4 in live cell membranes, only 47% of the NMO sera reacted with peptides originating from loops A, C, and E using ELISA and Western Blot, with the detected loop C antibody being highly specific to NMO.…”

“…In an earlier study [28], it was shown that several proteins in nature have a significant similarity in sequence and structure to human AQP4. The researchers found that IgG from the sera of patients with NMO cross-reacted with a sequence found in plant aquaporins and that this reactivity was much higher in NMO patients than in controls.…”

“…The researchers found that IgG from the sera of patients with NMO cross-reacted with a sequence found in plant aquaporins and that this reactivity was much higher in NMO patients than in controls. However, only 9 patients and 9 controls were involved in this study [28], and no IgM or IgA antibody measurements were done. For this reason, we wanted to examine whether or not this immunoreactivity to aquaporins is unique to NMO or could also be detected in patients with RRMS.…”

Glyphosate pathways to modern diseases VI: Prions, amyloidoses and autoimmune neurological diseases

“…Thus, aquaporins are implicated in brain oedema [180]. Plants produce aquaporins as well, and mimicry between plant and human aquaporins has been proposed as a mechanism for the development of an autoimmune sensitivity to this protein [181]. Plants considered to show aquaporin mimicry notably include corn and soy as well as tomato, tobacco and spinach [182].…”

Acute Myelopathy or Cauda Equina Syndrome in HIV-Positive Adults in a Tuberculosis Endemic Setting: MRI, Clinical, and Pathologic Findings

“…Explained by molecular mimicry, inflammation and damage to the spinal cord occur secondary to a shared antigenic profile between an invading virus, bacterium or plant protein, and spinal cord tissue. 27 Aquaporin 4 antibody levels were not done routinely at the time of our study. Long segment cord signal abnormality is also described with B 12 deficiency, though no documented cases of pernicious anemia were encountered in our group.…”