PMID- 32152690
OWN - NLM
STAT- MEDLINE
DCOM- 20210412
LR  - 20210619
IS  - 1432-1459 (Electronic)
IS  - 0340-5354 (Linking)
VI  - 267
IP  - 7
DP  - 2020 Jul
TI  - Primary DQ effect in the association between HLA and neurological syndromes with 
      anti-GAD65 antibodies.
PG  - 1906-1911
LID - 10.1007/s00415-020-09782-8 [doi]
AB  - The primary cause of neurological syndromes with antibodies against glutamic acid 
      decarboxylase 65 (GAD65-Ab) is unknown, but genetic predisposition may exist as 
      it is suggested by the co-occurrence in patients and their relatives of other 
      organ-specific autoimmune diseases, notably type 1 diabetes mellitus (T1DM), and 
      by the reports of a few familial cases. We analyzed the human leukocyte antigen 
      (HLA) in 32 unrelated patients and compared them to an ethnically matched sample 
      of 137 healthy controls. Four-digit resolution HLA alleles were imputed from 
      available Genome Wide Association data, and full HLA next-generation 
      sequencing-based typing was also performed. HLA DQA1*05:01-DQB1*02:01-DRB1*03:01 
      was the most frequent class II haplotype in patients (13/32, 41%). DQB1*02:01 was 
      the only allele found to be significantly more common in patients than in 
      controls (20/137, 15%, corrected p = 0.03, OR 3.96, 95% CI [1.54-10.09]). There 
      was also a trend towards more frequent DQA1*05:01 among patients compared to 
      controls (22/137, 16%; corrected p = 0.05, OR 3.54, 95% CI [1.40-8.91]) and 
      towards a protective effect of DQB1*03:01 (2/32, 6% in patients vs. 42/137, 31% 
      in control group; corrected p = 0.05, OR 0.15, 95% CI [0.02-0.65]). There was no 
      significant demographic or clinical difference between DQ2 and non-DQ2 carriers 
      (p > 0.05). Taken together, these findings suggest a primary DQ effect on 
      GAD65-Ab neurological diseases, partially shared with other systemic 
      organ-specific autoimmune diseases such as T1DM. However, it is likely that other 
      non-HLA loci are involved in the genetic predisposition of GAD65-Ab neurological 
      syndromes.
FAU - Muniz-Castrillo, Sergio
AU  - Muniz-Castrillo S
AUID- ORCID: 0000-0001-5958-3288
AD  - French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune 
      Encephalitis, Hospices Civils de Lyon, Hopital Neurologique, 59 Boulevard Pinel, 
      69677, Bron Cedex, France.
AD  - SynatAc Team, Institute NeuroMyoGene, INSERM U1217/CNRS UMR 5310, Universite de 
      Lyon, Universite Claude Bernard Lyon 1, Lyon, France.
FAU - Ambati, Aditya
AU  - Ambati A
AD  - Center for Sleep Sciences and Medicine, Stanford University, Palo Alto, CA, USA.
FAU - Dubois, Valerie
AU  - Dubois V
AD  - HLA Laboratory, French Blood Service, EFS Auvergne-Rhone-Alpes, Lyon, France.
FAU - Vogrig, Alberto
AU  - Vogrig A
AD  - French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune 
      Encephalitis, Hospices Civils de Lyon, Hopital Neurologique, 59 Boulevard Pinel, 
      69677, Bron Cedex, France.
AD  - SynatAc Team, Institute NeuroMyoGene, INSERM U1217/CNRS UMR 5310, Universite de 
      Lyon, Universite Claude Bernard Lyon 1, Lyon, France.
FAU - Joubert, Bastien
AU  - Joubert B
AD  - French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune 
      Encephalitis, Hospices Civils de Lyon, Hopital Neurologique, 59 Boulevard Pinel, 
      69677, Bron Cedex, France.
AD  - SynatAc Team, Institute NeuroMyoGene, INSERM U1217/CNRS UMR 5310, Universite de 
      Lyon, Universite Claude Bernard Lyon 1, Lyon, France.
FAU - Rogemond, Veronique
AU  - Rogemond V
AD  - French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune 
      Encephalitis, Hospices Civils de Lyon, Hopital Neurologique, 59 Boulevard Pinel, 
      69677, Bron Cedex, France.
AD  - SynatAc Team, Institute NeuroMyoGene, INSERM U1217/CNRS UMR 5310, Universite de 
      Lyon, Universite Claude Bernard Lyon 1, Lyon, France.
FAU - Picard, Geraldine
AU  - Picard G
AD  - French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune 
      Encephalitis, Hospices Civils de Lyon, Hopital Neurologique, 59 Boulevard Pinel, 
      69677, Bron Cedex, France.
AD  - SynatAc Team, Institute NeuroMyoGene, INSERM U1217/CNRS UMR 5310, Universite de 
      Lyon, Universite Claude Bernard Lyon 1, Lyon, France.
FAU - Lin, Ling
AU  - Lin L
AD  - Center for Sleep Sciences and Medicine, Stanford University, Palo Alto, CA, USA.
FAU - Fabien, Nicole
AU  - Fabien N
AD  - Department of Immunology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, 
      Lyon, France.
FAU - Mignot, Emmanuel
AU  - Mignot E
AD  - Center for Sleep Sciences and Medicine, Stanford University, Palo Alto, CA, USA.
FAU - Honnorat, Jerome
AU  - Honnorat J
AD  - French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune 
      Encephalitis, Hospices Civils de Lyon, Hopital Neurologique, 59 Boulevard Pinel, 
      69677, Bron Cedex, France. jerome.honnorat@chu-lyon.fr.
AD  - SynatAc Team, Institute NeuroMyoGene, INSERM U1217/CNRS UMR 5310, Universite de 
      Lyon, Universite Claude Bernard Lyon 1, Lyon, France. 
      jerome.honnorat@chu-lyon.fr.
LA  - eng
GR  - ANR-14-CE15-0001-MECANO/ANR France/
GR  - ANR-18-RHUS-0012-BETPSY/ANR France/
GR  - DQ20170336751/Fondation pour la Recherche Medicale/
PT  - Journal Article
DEP - 20200309
PL  - Germany
TA  - J Neurol
JT  - Journal of neurology
JID - 0423161
RN  - 0 (Autoantibodies)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ alpha-Chains)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQA1 antigen)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (HLA-DRB1 Chains)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
RN  - EC 4.1.1.15 (glutamate decarboxylase 2)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - *Autoantibodies/blood/cerebrospinal fluid
MH  - *Cerebellar Ataxia/genetics/immunology/metabolism
MH  - Comorbidity
MH  - *Diabetes Mellitus, Type 1/genetics/immunology/metabolism
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Glutamate Decarboxylase/*immunology
MH  - HLA-DQ Antigens/*genetics
MH  - HLA-DQ alpha-Chains/genetics
MH  - HLA-DQ beta-Chains/genetics
MH  - HLA-DRB1 Chains/genetics
MH  - Haplotypes
MH  - Humans
MH  - *Limbic Encephalitis/genetics/immunology/metabolism
MH  - Male
MH  - Middle Aged
MH  - *Stiff-Person Syndrome/genetics/immunology/metabolism
MH  - Young Adult
OTO - NOTNLM
OT  - Cerebellar ataxia
OT  - Glutamic acid decarboxylase
OT  - HLA
OT  - Limbic encephalitis
OT  - Stiff person syndrome
EDAT- 2020/03/11 06:00
MHDA- 2021/04/13 06:00
CRDT- 2020/03/11 06:00
PHST- 2019/11/28 00:00 [received]
PHST- 2020/03/04 00:00 [accepted]
PHST- 2020/03/02 00:00 [revised]
PHST- 2020/03/11 06:00 [pubmed]
PHST- 2021/04/13 06:00 [medline]
PHST- 2020/03/11 06:00 [entrez]
AID - 10.1007/s00415-020-09782-8 [pii]
AID - 10.1007/s00415-020-09782-8 [doi]
PST - ppublish
SO  - J Neurol. 2020 Jul;267(7):1906-1911. doi: 10.1007/s00415-020-09782-8. Epub 2020 
      Mar 9.