Antibody against α-gliadin 33-mer peptide: Is the key initiating factor for development of multiple sclerosis during gluten sensitivity?
Message:
Abstract:
Despite great advances in clarifying the pathogenesis of multiple sclerosis (MS), the exact underlying mechanism has not been definitely established. However, the responsibility of cross-reactive antibodies as the initiating factor in MS pathogenesis is a novel idea. Recently, an antibody against-α-gliadin 33-mer peptide which is found in most patients with gluten sensitivity have shown to cross-react significantly with various neural antigens including asialoganglioside, synapsin, and myelin basic protein (MBP). Furthermore, evidence indicates that IL-17, circulating immune complexes and even antibodies produced during gluten sensitivity can contribute to blood–brain barrier (BBB) permeability. Accordingly, extravasation of these anti-α-gliadin antibodies (AGA; especially IgG isotype) through the impaired BBB thought to target asialoganglioside, synapsin, and MBP in neurons. This opsonization may trigger a series of cascade pathways including complement activation, antibody-dependent microglial cytotoxicity against neurons, secretion of inflammatory mediators, myelin sheath damage, chemokine expression, CNS inflammation, BBB disruption and then leukocyte infiltration. The present hypothesis introduces a new antibody-dependent alternative pathway which may lead to multiple sclerosis (MS) during gluten sensitivity.
Language:
English
Published:
Journal of Medical Hypotheses and Ideas, Volume:9 Issue:1, 2015
Pages:
38 - 44
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