Increased IgA-mediated responses to the gut paracellular pathway and blood–brain barrier proteins predict delirium due to hip fracture in older adults

Abstract

IntroductionDelirium is accompanied by immune response system activation, which may, in theory, cause a breakdown of the gut barrier and blood–brain barrier (BBB). Some results suggest that the BBB is compromised in delirium, but there is no data regarding the gut barrier. This study investigates whether delirium is associated with impaired BBB and gut barriers in elderly adults undergoing hip fracture surgery.MethodsWe recruited 59 older adults and measured peak Delirium Rating Scale (DRS) scores 2–3 days after surgery, and assessed plasma IgG/IgA levels (using ELISA techniques) for zonulin, occludin, claudin-6, β-catenin, actin (indicating damage to the gut paracellular pathway), claudin-5 and S100B (reflecting BBB damage), bacterial cytolethal distending toxin (CDT), LPS-binding protein (LBP), lipopolysaccharides (LPS), Porphyromonas gingivalis, and Helicobacter pylori.ResultsResults from univariate analyses showed that delirium is linked to increased IgA responses to all the self-epitopes and antigens listed above, except for LPS. Part of the variance (between 45–48.3%) in the peak DRS score measured 2–3 days post-surgery was explained by independent effects of IgA directed to LPS and LBP (or bacterial CDT), baseline DRS scores, and previous mild stroke. Increased IgA reactivity to the paracellular pathway and BBB proteins and bacterial antigens is significantly associated with the activation of M1 macrophage, T helper-1, and 17 cytokine profiles.ConclusionHeightened bacterial translocation, disruption of the tight and adherens junctions of the gut and BBB barriers, elevated CDT and LPS load in the bloodstream, and aberrations in cell–cell interactions may be risk factors for delirium.

From HHV-6 reactivation to autoimmune reactivity against tight junctions and neuronal antigens, to inflammation, depression, and chronic fatigue syndrome due to Long COVID

“…Especially, the translocation into the blood of gut microbes with components that have structural relatedness with the tissues or cells of the human host are involved in this process, labeled molecular mimicry [24, 31, 63]. The factors that can lead to the production of cross-reactive antibodies include various components such as LPS from Gram-negative enterobacteria, bacterial cytolethal distending toxin (CDT), Gram-positive bacteria, and various viruses [64–67]. There are distinct mechanisms by which pathogens can trigger the development of autoimmune processes.…”

“…Gram-positive bacteria, and various viruses [64][65][66][67]. There are distinct mechanisms by which pathogens can trigger the development of autoimmune processes.…”