PMID- 37306550
OWN - NLM
STAT- MEDLINE
DCOM- 20230808
LR  - 20230809
IS  - 1468-1331 (Electronic)
IS  - 1351-5101 (Linking)
VI  - 30
IP  - 9
DP  - 2023 Sep
TI  - Risk of a first clinical diagnosis of central nervous system demyelination in 
      relation to human herpesviruses in the context of Epstein-Barr virus.
PG  - 2752-2760
LID - 10.1111/ene.15919 [doi]
AB  - BACKGROUND AND PURPOSE: Epstein-Barr virus (EBV) is implicated in multiple 
      sclerosis (MS) risk; evidence for other herpesviruses is inconsistent. Here, we 
      test blood markers of infection with human herpesvirus 6 (HHV-6), varicella 
      zoster virus (VZV), and cytomegalovirus (CMV) as risk factors for a first 
      clinical diagnosis of central nervous system demyelination (FCD) in the context 
      of markers of EBV infection. METHODS: In the Ausimmune case-control study, cases 
      had an FCD, and population controls were matched on age, sex, and study region. 
      We quantified HHV-6- and VZV-DNA load in whole blood and HHV-6, VZV, and CMV 
      antibodies in serum. Conditional logistic regression tested associations with FCD 
      risk, adjusting for Epstein-Barr nuclear antigen (EBNA) IgG, EBV-DNA load, and 
      other covariates. RESULTS: In 204 FCD cases and 215 matched controls, only 
      HHV-6-DNA load (positive vs. negative) was associated with FCD risk (adjusted 
      odds ratio = 2.20, 95% confidence interval = 1.08-4.46, p = 0.03). Only EBNA IgG 
      and HHV-6-DNA positivity were retained in a predictive model of FCD risk; the 
      combination had a stronger association than either alone. CMV-specific IgG 
      concentration modified the association between an MS risk-related human leucocyte 
      antigen gene and FCD risk. Six cases and one control had very high HHV-6-DNA load 
      (>1.0 x 10(6) copies/mL). CONCLUSIONS: HHV-6-DNA positivity and high load 
      (possibly due to inherited HHV-6 chromosomal integration) were associated with 
      increased FCD risk, particularly in association with markers of EBV infection. 
      With growing interest in prevention/management of MS through EBV-related 
      pathways, there should be additional consideration of the role of HHV-6 
      infection.
CI  - (c) 2023 The Authors. European Journal of Neurology published by John Wiley & Sons 
      Ltd on behalf of European Academy of Neurology.
FAU - Lucas, Robyn M
AU  - Lucas RM
AUID- ORCID: 0000-0003-2736-3541
AD  - National Centre for Epidemiology and Population Health, Australian National 
      University, Canberra, Australian Capital Territory, Australia.
FAU - Lay, Meav-Lang J
AU  - Lay MJ
AD  - Clinical Virology Department, Centre for Infectious Diseases & Microbiology 
      Laboratory Services, Institute of Clinical Pathology & Medical Research, Westmead 
      Hospital, Westmead, New South Wales, Australia.
FAU - Grant, James
AU  - Grant J
AD  - ANU Medical School, Australian National University, Canberra, Australian Capital 
      Territory, Australia.
FAU - Cherbuin, Nicolas
AU  - Cherbuin N
AUID- ORCID: 0000-0001-6481-0748
AD  - National Centre for Epidemiology and Population Health, Australian National 
      University, Canberra, Australian Capital Territory, Australia.
FAU - Toi, Cheryl S
AU  - Toi CS
AD  - Clinical Virology Department, Centre for Infectious Diseases & Microbiology 
      Laboratory Services, Institute of Clinical Pathology & Medical Research, Westmead 
      Hospital, Westmead, New South Wales, Australia.
FAU - Dear, Keith
AU  - Dear K
AD  - University of Adelaide, Adelaide, South Australia, Australia.
FAU - Taylor, Bruce V
AU  - Taylor BV
AD  - Menzies Research Institute Tasmania, Hobart, Tasmania, Australia.
FAU - Dwyer, Dominic E
AU  - Dwyer DE
AD  - Clinical Virology Department, Centre for Infectious Diseases & Microbiology 
      Laboratory Services, Institute of Clinical Pathology & Medical Research, Westmead 
      Hospital, Westmead, New South Wales, Australia.
CN  - Ausimmune Investigator Group
FAU - Ponsonby, Anne-Louise
AU  - Ponsonby AL
AD  - Howard Florey Institute, Melbourne, Victoria, Australia.
LA  - eng
GR  - MSS_/Multiple Sclerosis Society/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230623
PL  - England
TA  - Eur J Neurol
JT  - European journal of neurology
JID - 9506311
RN  - 0 (Immunoglobulin G)
SB  - IM
MH  - Humans
MH  - Herpesvirus 4, Human
MH  - *Epstein-Barr Virus Infections/complications
MH  - Case-Control Studies
MH  - *Herpesvirus 6, Human/genetics
MH  - *Multiple Sclerosis
MH  - Herpesvirus 3, Human/genetics
MH  - *Cytomegalovirus Infections
MH  - Immunoglobulin G
MH  - Central Nervous System
OTO - NOTNLM
OT  - case-control
OT  - human herpesviruses
OT  - multiple sclerosis
OT  - viral infections
FIR - Chapman, Caron
IR  - Chapman C
FIR - Coulthard, Alan
IR  - Coulthard A
FIR - Dear, Keith
IR  - Dear K
FIR - Dwyer, Terry
IR  - Dwyer T
FIR - Kilpatrick, Trevor
IR  - Kilpatrick T
FIR - Lucas, Robyn
IR  - Lucas R
FIR - McMichael, Tony
IR  - McMichael T
FIR - Ponsonby, Anne-Louise
IR  - Ponsonby AL
FIR - Taylor, Bruce
IR  - Taylor B
FIR - Valery, Patricia
IR  - Valery P
FIR - van der Mei, Ingrid
IR  - van der Mei I
FIR - Williams, David
IR  - Williams D
EDAT- 2023/06/12 13:06
MHDA- 2023/08/08 06:42
CRDT- 2023/06/12 09:44
PHST- 2023/04/26 00:00 [revised]
PHST- 2023/02/26 00:00 [received]
PHST- 2023/06/07 00:00 [accepted]
PHST- 2023/08/08 06:42 [medline]
PHST- 2023/06/12 13:06 [pubmed]
PHST- 2023/06/12 09:44 [entrez]
AID - 10.1111/ene.15919 [doi]
PST - ppublish
SO  - Eur J Neurol. 2023 Sep;30(9):2752-2760. doi: 10.1111/ene.15919. Epub 2023 Jun 23.