Antibodies against small heat-shock proteins in Alzheimer’s disease as a part of natural human immune repertoire or activation of humoral response?

Abstract

Characterization of autoantibodies specific for some disease-related proteins, would allow to better assess their role as diagnostic and prognostic markers. In the light of increasing evidence for both humoral and cellular adaptive immune responses in the pathophysiology of Alzheimer’s disease (AD), and data on the increased small heat-shock proteins (sHSP) expression in this disease, it seemed justified to assess humoral response against sHSP in AD patients. The aim of the study was to check whether AD has the ability to elicit immune response against small HSP, which could also serve as disease biomarkers. IgG and IgM autoantibodies against alpha B-crystallin and anti-HSP 60 IgG autoantibodies were assessed in 59 AD patients and 59 healthy subjects. Both IgM and IgG autoantibodies against alpha B-crystallin in AD patients were significantly higher compared to healthy controls (p < 0.05). No statistically significant differences were found between AD patients and healthy subjects were found in anti-HSP60 IgG autoantibody titers (p = 0.29). Anti-HSP60 antibodies present in AD patients may indeed belong to natural human immune repertoire, and chronic neurodegenerative process does not have significant inducing effect on the systemic immunoreactivity against HSP60. Increased titers of IgM and IgG autoantibodies against alpha B-crystallin in AD patients may reflect activation of humoral immune response in the course of this chronic disease, probably secondary to its increased expression. Further prospective studies, on larger group of AD patients and measuring a change in antibodies titers with disease progression are necessary to assess the exact role of these antibodies in AD.

Small Heat Shock Proteins, Big Impact on Protein Aggregation in Neurodegenerative Disease

“…Elevated HspB1 protein levels in serum have been detected in multiple sclerosis (Ce et al, 2011) and in both plasma and cerebrospinal fluid during ischemia (Hecker and McGarvey, 2011). The presence of HspB5 autoantibodies in the serum of AD and PD patients provides additional evidence for the presence of extracellular sHsps in neurodegenerative disease (Papuć et al, 2015; Papuć et al, 2016). sHsp secretion appears to be regulated by post-translational modifications.…”

The Functional Roles and Applications of Immunoglobulins in Neurodegenerative Disease

“…The levels of autoantibodies targeting ATP synthase, angiotensin II type 1, and 5-hydroxytryptamine also are altered in AD [ 44 ]. The concentration of IgM and IgG autoantibodies targeting alpha B-crystallin is increased in AD patients [ 45 ]. These data suggest that some types of Ig have functional roles related to AD pathogenesis.…”

Review: Impact of Helicobacter pylori on Alzheimer's disease: What do we know so far?

“…There is an increasing evidence of both humoral and cellular adaptive immune responses involved in the pathophysiology of AD . In AD, molecular and cellular alterations involving TLs and immune mediators occur not only in the brain, but also in the blood and the cerebrospinal fluid (CSF); peripheral TLs can cross the mentioned disrupted BBB and the blood‐CSF barrier and access the brain, thereby supporting the proinflammatory role of TLs infiltrating the AD brain .…”