PMID- 31577807
OWN - NLM
STAT- MEDLINE
DCOM- 20200310
LR  - 20200310
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 14
IP  - 10
DP  - 2019
TI  - HLA high-resolution typing by next-generation sequencing in Pandemrix-induced 
      narcolepsy.
PG  - e0222882
LID - 10.1371/journal.pone.0222882 [doi]
LID - e0222882
AB  - The incidence of narcolepsy type 1 (NT1) increased in Sweden following the 
      2009-2010 mass-vaccination with the influenza Pandemrix-vaccine. NT1 has been 
      associated with Human leukocyte antigen (HLA) DQB1*06:02 but full high-resolution 
      HLA-typing of all loci in vaccine-induced NT1 remains to be done. Therefore, here 
      we performed HLA typing by sequencing HLA-DRB3, DRB4, DRB5, DRB1, DQA1, DQB1, 
      DPA1 and DPB1 in 31 vaccine-associated NT1 patients and 66 of their first-degree 
      relatives (FDR), and compared these data to 636 Swedish general population 
      controls (GP). Previously reported disease-related alleles in the 
      HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02:01-DQB1*06:02:01 extended haplotype 
      were increased in NT1 patients (34/62 haplotypes, 54.8%) compared to GP (194/1272 
      haplotypes, 15.3%, p = 6.17E-16). Indeed, this extended haplotype was found in 
      30/31 patients (96.8%) and 178/636 GP (28.0%). In total, 15 alleles, four 
      extended haplotypes, and six genotypes were found to be increased or decreased in 
      frequency among NT1 patients compared to GP. Among subjects with the 
      HLA-DRB5*01:01:01-DRB1*15:01:01-DQA1*01:02-DQB1*06:02 haplotype, a second 
      DRB4*01:03:01-DRB1*04:01:01-DQA1*03:02//*03:03:01-DQB1*03:01:01 haplotype (p = 
      2.02E-2), but not homozygosity for DRB1*15:01:01-DQB1*06:02:01 (p = 7.49E-1) 
      conferred association to NT1. Alleles with increased frequency in DQA1*01:02:01 
      (p = 1.07E-2) and DQA1*03:02//*03:03:01 (p = 3.26E-2), as well as with decreased 
      frequency in DRB3*01:01:02 (p = 8.09E-3), DRB1*03:01:01 (p = 1.40E-2), and 
      DQB1*02:01:01 (p = 1.40E-2) were found among patients compared to their FDR. 
      High-resolution HLA sequencing in Pandemrix-associated NT1 confirmed the strong 
      association with the DQB1*06:02:01-containing haplotype but also revealed an 
      increased association to the not previously reported extended 
      HLA-DRB4*01:03:01-DRB1*04:01:01-DQA1*03:02//*03:03:01-DQB1*03:01:01 haplotype. 
      High-resolution HLA typing should prove useful in dissecting the immunological 
      mechanisms of vaccination-associated NT1.
FAU - Lind, Alexander
AU  - Lind A
AUID- ORCID: 0000-0002-1473-5468
AD  - Department of Clinical Sciences Malmo, Lund University/CRC, Skane University 
      Hospital SUS, Malmo, Sweden.
FAU - Akel, Omar
AU  - Akel O
AD  - Department of Clinical Sciences Malmo, Lund University/CRC, Skane University 
      Hospital SUS, Malmo, Sweden.
FAU - Wallenius, Madeleine
AU  - Wallenius M
AD  - Department of Clinical Sciences Malmo, Lund University/CRC, Skane University 
      Hospital SUS, Malmo, Sweden.
FAU - Ramelius, Anita
AU  - Ramelius A
AD  - Department of Clinical Sciences Malmo, Lund University/CRC, Skane University 
      Hospital SUS, Malmo, Sweden.
FAU - Maziarz, Marlena
AU  - Maziarz M
AUID- ORCID: 0000-0003-1417-6050
AD  - Department of Clinical Sciences Malmo, Lund University/CRC, Skane University 
      Hospital SUS, Malmo, Sweden.
FAU - Zhao, Lue Ping
AU  - Zhao LP
AD  - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, 
      Washington, United States of America.
FAU - Geraghty, Daniel E
AU  - Geraghty DE
AD  - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, 
      Washington, United States of America.
FAU - Palm, Lars
AU  - Palm L
AD  - Section for Paediatric Neurology, Department of Paediatrics, Skane University 
      Hospital SUS, Malmo, Sweden.
FAU - Lernmark, Ake
AU  - Lernmark A
AD  - Department of Clinical Sciences Malmo, Lund University/CRC, Skane University 
      Hospital SUS, Malmo, Sweden.
FAU - Larsson, Helena Elding
AU  - Larsson HE
AD  - Department of Clinical Sciences Malmo, Lund University/CRC, Skane University 
      Hospital SUS, Malmo, Sweden.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191002
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (HLA Antigens)
RN  - 0 (Influenza Vaccines)
RN  - 0 (pandemrix)
SB  - IM
MH  - Alleles
MH  - Genetic Predisposition to Disease
MH  - HLA Antigens/genetics
MH  - Haplotypes/genetics
MH  - *High-Throughput Nucleotide Sequencing
MH  - Histocompatibility Testing/*methods
MH  - Humans
MH  - Influenza Vaccines/*adverse effects
MH  - Narcolepsy/*chemically induced/*genetics
PMC - PMC6774514
COIS- The authors have declared that no competing interests exist.
EDAT- 2019/10/03 06:00
MHDA- 2020/03/11 06:00
PMCR- 2019/10/02
CRDT- 2019/10/03 06:00
PHST- 2019/03/26 00:00 [received]
PHST- 2019/09/09 00:00 [accepted]
PHST- 2019/10/03 06:00 [entrez]
PHST- 2019/10/03 06:00 [pubmed]
PHST- 2020/03/11 06:00 [medline]
PHST- 2019/10/02 00:00 [pmc-release]
AID - PONE-D-19-08679 [pii]
AID - 10.1371/journal.pone.0222882 [doi]
PST - epublish
SO  - PLoS One. 2019 Oct 2;14(10):e0222882. doi: 10.1371/journal.pone.0222882. 
      eCollection 2019.