PMID- 36520371
OWN - NLM
STAT- MEDLINE
DCOM- 20230228
LR  - 20230313
IS  - 1878-7649 (Print)
IS  - 1878-7649 (Linking)
VI  - 14
IP  - 1
DP  - 2023 Feb
TI  - 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.
PG  - 99-112
LID - 10.1007/s41999-022-00729-y [doi]
AB  - 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(1) (NR(1)) and GLU(2) 
      (NR(2)), 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.
CI  - (c) 2022. The Author(s), under exclusive licence to European Geriatric Medicine 
      Society.
FAU - Maes, Michael
AU  - Maes M
AUID- ORCID: 0000-0002-2012-871X
AD  - Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, 
      Thailand. dr.michaelmaes@hotmail.com.
AD  - Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria. 
      dr.michaelmaes@hotmail.com.
AD  - IMPACT Strategic Research Center, Deakin University, Geelong, Australia. 
      dr.michaelmaes@hotmail.com.
FAU - Thisayakorn, Paul
AU  - Thisayakorn P
AD  - Department of Psychiatry, Hip Fracture Research Unit, Faculty of Medicine, 
      Chulalongkorn University, Bangkok, Thailand. paul.thi@chula.ac.th.
FAU - Thipakorn, Yanin
AU  - Thipakorn Y
AD  - Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, 
      Thailand.
FAU - Tantavisut, Saran
AU  - Tantavisut S
AD  - Department of Orthopedics, Hip Fracture Research Unit, Faculty of Medicine, 
      Chulalongkorn University, Bangkok, Thailand.
FAU - Sirivichayakul, Sunee
AU  - Sirivichayakul S
AD  - Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, 
      Thailand.
FAU - Vojdani, Aristo
AU  - Vojdani A
AD  - Immunosciences Lab. Inc, Los Angeles, CA, USA.
AD  - Cyrex Labs LLC, Phoeniz, AZ, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221215
PL  - Switzerland
TA  - Eur Geriatr Med
JT  - European geriatric medicine
JID - 101533694
RN  - 0 (Aquaporin 4)
RN  - 0 (Chaperonin 60)
RN  - 0 (Epitopes)
RN  - 0 (Immunoglobulin A)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Myelin-Oligodendrocyte Glycoprotein)
RN  - 0 (Neurofilament Proteins)
RN  - 0 (HSPD1 protein, human)
RN  - 0 (AQP4 protein, human)
SB  - IM
MH  - Humans
MH  - *Aquaporin 4/metabolism
MH  - Chaperonin 60/metabolism
MH  - *Delirium/etiology
MH  - Epitopes
MH  - Immunoglobulin A/metabolism
MH  - Immunoglobulin G/metabolism
MH  - Myelin-Oligodendrocyte Glycoprotein/metabolism
MH  - Neurofilament Proteins/metabolism
OTO - NOTNLM
OT  - Biomarkers
OT  - Delirium
OT  - Inflammation
OT  - Neuro-immune
OT  - Polyreactive antibodies
OT  - Psychiatry
EDAT- 2022/12/16 06:00
MHDA- 2023/02/09 06:00
CRDT- 2022/12/15 11:20
PHST- 2022/08/28 00:00 [received]
PHST- 2022/12/04 00:00 [accepted]
PHST- 2022/12/16 06:00 [pubmed]
PHST- 2023/02/09 06:00 [medline]
PHST- 2022/12/15 11:20 [entrez]
AID - 10.1007/s41999-022-00729-y [pii]
AID - 10.1007/s41999-022-00729-y [doi]
PST - ppublish
SO  - Eur Geriatr Med. 2023 Feb;14(1):99-112. doi: 10.1007/s41999-022-00729-y. Epub 
      2022 Dec 15.