PMID- 35959717
OWN - NLM
STAT- MEDLINE
DCOM- 20220907
LR  - 20221015
IS  - 1744-313X (Electronic)
IS  - 1744-3121 (Print)
IS  - 1744-3121 (Linking)
VI  - 49
IP  - 5
DP  - 2022 Oct
TI  - High-resolution HLA class II sequencing of Swedish multiple sclerosis patients.
PG  - 333-339
LID - 10.1111/iji.12594 [doi]
AB  - Multiple sclerosis (MS) is a chronic neurological disease believed to be caused 
      by autoimmune pathogenesis. The aetiology is likely explained by a complex 
      interplay between inherited and environmental factors. Genetic investigations 
      into MS have been conducted for over 50 years, yielding >100 associations to 
      date. Globally, the strongest linkage is with the human leukocyte antigen (HLA) 
      HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01 haplotype. Here, 
      high-resolution sequencing of HLA was used to determine the alleles of DRB3, 
      DRB4, DRB5, DRB1, DQA1, DQB1, DPA1 and DPB1 as well as their extended haplotypes 
      and genotypes in 100 Swedish MS patients. Results were compared to 636 population 
      controls. The heterogeneity in HLA associations with MS was demonstrated; among 
      100 patients, 69 extended HLA-DR-DQ genotypes were found. Three extended 
      HLA-DR-DQ genotypes were found to be correlated to MS; 
      HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01 haplotype together 
      with (A) 
      HLA-DRB4*01:01:01//DRB4*01:01:01:01-DRB1*07:01:01-DQA1*02:01//02:01:01-DQB1*02:02:01, 
      (B) HLA-DRBX*null-DRB1*08:01:01-DQA1*04:01:01-DQB1*04:02:01, and (C) 
      HLA-DRB3*01:01:02-DRB1*03:01:01-DQA1*05:01:01-DQB1*02:01:01. At the allelic 
      level, HLA-DRB3*01:01:02 was considered protective against MS. However, when 
      combined with HLA-DRB3*01:01:02-DRB1*03:01:01-DQA1*05:01:01-DQB1*02:01:01, this 
      extended haplotype was considered a predisposing risk factor. This highlights the 
      limitations as included with investigations of single alleles relative to those 
      of extended haplotypes/genotypes. In conclusion, with 69 genotypes presented 
      among 100 patients, high-resolution sequencing was conducted to underscore the 
      wide polymorphisms present among MS patients. Additional studies in larger 
      cohorts will be of importance to define MS among the patient group not associated 
      with HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01.
CI  - (c) 2022 The Authors. International Journal of Immunogenetics published by John 
      Wiley & Sons Ltd.
FAU - Akel, Omar
AU  - Akel O
AD  - Department of Clinical Sciences Malmo, Clinical Research Centre, Lund University, 
      Skane University Hospital SUS, Malmo, Sweden.
FAU - Zhao, Lue Ping
AU  - Zhao LP
AD  - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 
      United States.
FAU - Geraghty, Daniel E
AU  - Geraghty DE
AD  - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 
      United States.
FAU - Lind, Alexander
AU  - Lind A
AD  - Department of Clinical Sciences Malmo, Clinical Research Centre, Lund University, 
      Skane University Hospital SUS, Malmo, Sweden.
LA  - eng
PT  - Journal Article
DEP - 20220812
PL  - England
TA  - Int J Immunogenet
JT  - International journal of immunogenetics
JID - 101232337
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-DQ alpha-Chains)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB3 Chains)
RN  - 0 (HLA-DRB5 Chains)
SB  - IM
MH  - HLA Antigens
MH  - HLA-DQ alpha-Chains/genetics
MH  - HLA-DQ beta-Chains/genetics
MH  - HLA-DRB1 Chains/genetics
MH  - HLA-DRB3 Chains/genetics
MH  - HLA-DRB5 Chains/genetics
MH  - Haplotypes
MH  - Humans
MH  - *Multiple Sclerosis/genetics
MH  - Sweden
PMC - PMC9545082
OTO - NOTNLM
OT  - autoimmunity
OT  - high-resolution sequencing
OT  - human leukocyte antigen
OT  - multiple sclerosis
COIS- There are no conflicts of interest.
EDAT- 2022/08/13 06:00
MHDA- 2022/09/08 06:00
PMCR- 2022/10/07
CRDT- 2022/08/12 05:42
PHST- 2022/07/20 00:00 [revised]
PHST- 2022/04/26 00:00 [received]
PHST- 2022/07/29 00:00 [accepted]
PHST- 2022/08/13 06:00 [pubmed]
PHST- 2022/09/08 06:00 [medline]
PHST- 2022/08/12 05:42 [entrez]
PHST- 2022/10/07 00:00 [pmc-release]
AID - IJI12594 [pii]
AID - 10.1111/iji.12594 [doi]
PST - ppublish
SO  - Int J Immunogenet. 2022 Oct;49(5):333-339. doi: 10.1111/iji.12594. Epub 2022 Aug 
      12.