Amyloids in Site-Specific Autoimmune Reactions and Inflammatory Responses

Abstract

Amyloid deposition is a histological hallmark of common human disorders including Alzheimer's disease (AD) and type 2 diabetes. Although some reports highlight that amyloid fibrils might activate the innate immunity system via pattern recognition receptors, here, we provide multiple lines of evidence for the protection by site-specific amyloid protein analogs and fibrils against autoimmune attacks: (1) strategies targeting clearance of the AD-related brain amyloid plaque induce high risk of deadly autoimmune destructions in subjects with cognitive dysfunction; (2) administration of amyloidogenic peptides with either full length or core hexapeptide structure consistently ameliorates signs of experimental autoimmune encephalomyelitis; (3) experimental autoimmune encephalomyelitis is exacerbated following genetic deletion of amyloid precursor proteins; (4) absence of islet amyloid coexists with T-cell-mediated insulitis in autoimmune diabetes and autoimmune polyendocrine syndrome; (5) use of islet amyloid polypeptide agonists rather than antagonists improves diabetes care; and (6) common suppressive signaling pathways by regulatory T cells are activated in both local and systemic amyloidosis. These findings indicate dual modulation activity mediated by amyloid protein monomers, oligomers, and fibrils to maintain immune homeostasis. The protection from autoimmune destruction by amyloid proteins offers a novel therapeutic approach to regenerative medicine for common degenerative diseases.

Amyloidosis: What does pathology offer? The evolving field of tissue biopsy

“…Although incidence of myocardial inflammation in cardiac amyloidosis is unknown, in our referral center, which handles many endomyocardial biopsies (EMBs) and numerous whole transplanted hearts of patients with amyloidosis, we had the opportunity to study myocardial inflammatory infiltrates associated to amyloid deposits, varying from simply lymphocytic or macrophagic-lymphocytic to giant cell granulomatous inflammation (Figure 5). Data are still scanty, but literature documented that amyloid may play a role in immune/autoimmune response (38). The issue of amyloidosis and inflammation is yet based on isolated and preliminary observations and research is needed to expand knowledge on pathogenetic mechanisms, possible role of inflammatory infiltrates on deposits, interactions with specific amyloidosis type and impact on disease progression and survival or on future therapeutic implication (39)(40)(41).…”

AGE/Non-AGE Glycation: An Important Event in Rheumatoid Arthritis Pathophysiology

“…It has also been reported that oxidative stress causes increased Aβ deposition and formation of aggregates in neuronal cells, which is recognized as a hallmark of AD. The differential analysis of Aβ peptides and amyloids proteins in RA will be an effective method that offers protection from an autoimmune response and cartilage destruction to inflammation [88].…”