Small intestinal enteropathy with epithelial IgG and complement deposition in children with regressive autism

Abstract

We have reported lymphocytic colitis in children with regressive autism, with epithelial damage prominent. We now compare duodenal biopsies in 25 children with regressive autism to 11 with coeliac disease, five with cerebral palsy and mental retardation and 18 histologically normal controls. Immunohistochemistry was performed for lymphocyte and epithelial lineage and functional markers. We determined the density of intraepithelial and lamina propria lymphocyte populations, and studied mucosal immunoglobulin and complement C1q localisation. Standard histopathology showed increased enterocyte and Paneth cell numbers in the autistic children. Immunohistochemistry demonstrated increased lymphocyte infiltration in both epithelium and lamina propria with upregulated crypt cell proliferation, compared to normal and cerebral palsy controls. Intraepithelial lymphocytes and lamina propria plasma cells were lower than in coeliac disease, but lamina propria T cell populations were higher and crypt proliferation similar. Most strikingly, IgG deposition was seen on the basolateral epithelial surface in 23/25 autistic children, co-localising with complement C1q. This was not seen in the other conditions. These findings demonstrate a novel form of enteropathy in autistic children, in which increases in mucosal lymphocyte density and crypt cell proliferation occur with epithelial IgG deposition. The features are suggestive of an autoimmune lesion.

Immune Dysfunction in Autism: A Pathway to Treatment

“…Notably, antibodies directed at gut epithelium have also been described in ASD children; 75 however, no link between gut and brain antibodies has yet been established.…”

Immune dysfunction and neuroinflammation in autism spectrum disorder

“…Also, postmortem temporal cortex samples from ASD and general population controls were assessed for transcriptome differences and it was observed that samples from ASD individuals showed increases in expression of immune-related genes (Garbett et al 2008). It was also previously revealed that individuals diagnosed with ASD in comparison to controls have an inflammatory response presenting as an increased lymphocytes and proinflammatory cytokines, including TNF-α and IFN-γ and less of the anti-inflammatory cytokine IL-10 (Torrente et al 2002, Ashwood et al 2004, Nakagawa and Chiba 2016. As a result, among individuals diagnosed with ASD, inflammation can become chronic.…”

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

“…He and several colleagues later published additional papers elaborating the hypothesis that dysbiosis in the gut, combined with impaired protein hydrolysis, leads to autoimmune lesions in the duodenum that are associated with extensive colonic lymphoid hyperplasia. The release of undigested peptides into the vasculature across a leaky gut barrier and, ultimately, from the vasculature across a leaky blood-brain barrier, could induce encephalopathy [165][166][167].…”