Reactivity to neural tissue epitopes, aquaporin 4 and heat shock protein 60 is associated with activated immune-inflammatory pathways and the onset of delirium following hip fracture surgery

Objectives Activation of the immune-inflammatory response system (IRS) and a deficiency in the compensatory immunoregulatory system (CIRS), neuronal injuries, and alterations in the glutamate receptor (GlutaR), aquaporin-4 (AQP4) and heat shock protein 60 (HSP60) are involved in delirium. Increased serum levels of neurofilament protein (NFP), glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) are biomarkers of neuronal injury. This investigation delineates whether elevated IgA/IgG reactivity against those self-antigens is associated with delirium severity and IRS activation. Methods We measured peak Delirium Rating Scale (DRS) scores on days 2 and 3 following surgery in 59 hip fractured older adults, and IgA and IgG antibody levels against MBP, NFP, GFAP and myelin oligodendrocyte glycoprotein (MOG), metabotropic glutamate receptors mGluRs 1 and 5, N-Methyl-D-Aspartate receptor (NMDAR) GLU T (NR1) and GLU(2) (NR2), APQ4 and HSP60. Results The IgA antibody levels against those self-antigens, especially GFAP, MBP and HSP60, strongly predict peak DRS scores on days 2 and 3 post-surgery. IgA reactivity against NMDAR and baseline DRS scores explained 40.6% of the variance in peak DRS scores, while IgA against NMDAR, IgG against MBP and age explained 29.1% of the variance in the IRS/CIRS ratio. There was no correlation between DRS scores and IgG directed against other self-antigens. Conclusions Increased IgA levels against neuronal self-antigens, AQP4 and HSP60 are risk factors for delirium. Polyreactive antibody-associated breakdown of immune tolerance, IRS activation and injuries in the neuronal cytoskeleton, oligodendrocytes, astrocytes, glial cells, and myelin sheath are involved in the pathophysiology of delirium.

Automated summary

This study found that elevated IgA levels against neuronal self-antigens, AQP4, and HSP60 are risk factors for delirium. The breakdown of immune tolerance, activation of the immune-inflammatory response system, and injuries in neuronal and glial cells are involved in the pathophysiology of delirium.