PMID- 33348629
OWN - NLM
STAT- MEDLINE
DCOM- 20210621
LR  - 20210621
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 9
IP  - 12
DP  - 2020 Dec 17
TI  - HLA Class II Genotype Does Not Affect the Myelin Responsiveness of Multiple 
      Sclerosis Patients.
LID - 10.3390/cells9122703 [doi]
LID - 2703
AB  - BACKGROUND: When aiming to restore myelin tolerance using antigen-specific 
      treatment approaches in MS, the wide variety of myelin-derived antigens towards 
      which immune responses are targeted in multiple sclerosis (MS) patients needs to 
      be taken into account. Uncertainty remains as to whether the myelin reactivity 
      pattern of a specific MS patient can be predicted based upon the human leukocyte 
      antigen (HLA) class II haplotype of the patient. METHODS: In this study, we 
      analyzed the reactivity towards myelin oligodendrocyte glycoprotein (MOG), myelin 
      basic protein (MBP) and proteolipid protein (PLP) peptides using direct 
      interferon (IFN)-gamma enzyme-linked immune absorbent spot (ELISPOT). Next, the HLA 
      class II haplotype profile was determined by next-generation sequencing. In doing 
      so, we aimed to evaluate the possible association between the precursor frequency 
      of myelin-reactive T cells and the HLA haplotype. RESULTS: Reactivity towards any 
      of the analyzed peptides could be demonstrated in 65.0% (13/20) of MS patients 
      and in 60.0% (6/10) of healthy controls. At least one of the MS risk alleles 
      HLA-DRB1*15:01, HLA-DQA1*01:02 and HLA-DQB1*06:02 was found in 70.0% (14/20) of 
      patients and in 20.0% (2/10) of healthy controls. No difference in the presence 
      of a myelin-specific response, nor in the frequency of myelin peptide-reactive 
      precursor cells could be detected among carriers and non-carriers of these risk 
      alleles. CONCLUSION: No association between HLA haplotype and myelin reactivity 
      profile was present in our study population. This complicates the development of 
      antigen-specific treatment approaches and implies the need for multi-epitope 
      targeting in an HLA-unrestricted manner to fully address the wide variation in 
      myelin responses and HLA profiles in a heterogeneous group of MS patients.
FAU - Derdelinckx, Judith
AU  - Derdelinckx J
AUID- ORCID: 0000-0003-0898-1432
AD  - Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute 
      (VaxInfectio), Faculty of Medicine and Health Sciences, University of Antwerp, 
      2610 Antwerp, Belgium.
AD  - Division of Neurology, Antwerp University Hospital, 2650 Edegem, Belgium.
FAU - Nkansah, Irene
AU  - Nkansah I
AD  - Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute 
      (VaxInfectio), Faculty of Medicine and Health Sciences, University of Antwerp, 
      2610 Antwerp, Belgium.
FAU - Ooms, Naomi
AU  - Ooms N
AD  - Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute 
      (VaxInfectio), Faculty of Medicine and Health Sciences, University of Antwerp, 
      2610 Antwerp, Belgium.
FAU - Van Bruggen, Laura
AU  - Van Bruggen L
AD  - Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute 
      (VaxInfectio), Faculty of Medicine and Health Sciences, University of Antwerp, 
      2610 Antwerp, Belgium.
FAU - Emonds, Marie-Paule
AU  - Emonds MP
AUID- ORCID: 0000-0002-2653-8656
AD  - Histocompatibility and Immunogenetics Laboratory, Red Cross-Flanders, 2650 
      Mechelen, Belgium.
FAU - Daniels, Liesbeth
AU  - Daniels L
AD  - Histocompatibility and Immunogenetics Laboratory, Red Cross-Flanders, 2650 
      Mechelen, Belgium.
FAU - Reynders, Tatjana
AU  - Reynders T
AUID- ORCID: 0000-0002-9263-0012
AD  - Division of Neurology, Antwerp University Hospital, 2650 Edegem, Belgium.
FAU - Willekens, Barbara
AU  - Willekens B
AUID- ORCID: 0000-0002-5212-8837
AD  - Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute 
      (VaxInfectio), Faculty of Medicine and Health Sciences, University of Antwerp, 
      2610 Antwerp, Belgium.
AD  - Division of Neurology, Antwerp University Hospital, 2650 Edegem, Belgium.
FAU - Cras, Patrick
AU  - Cras P
AD  - Division of Neurology, Antwerp University Hospital, 2650 Edegem, Belgium.
AD  - Born Bunge Institute, Translational Neurosciences, Faculty of Medicine and Health 
      Sciences, University of Antwerp, 2610 Antwerp, Belgium.
FAU - Berneman, Zwi N
AU  - Berneman ZN
AD  - Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute 
      (VaxInfectio), Faculty of Medicine and Health Sciences, University of Antwerp, 
      2610 Antwerp, Belgium.
AD  - Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, 
      2650 Edegem, Belgium.
FAU - Cools, Nathalie
AU  - Cools N
AD  - Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute 
      (VaxInfectio), Faculty of Medicine and Health Sciences, University of Antwerp, 
      2610 Antwerp, Belgium.
AD  - Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, 
      2650 Edegem, Belgium.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201217
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (HLA 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 (MBP protein, human)
RN  - 0 (Myelin Basic Protein)
RN  - 0 (Myelin Proteolipid Protein)
RN  - 0 (Myelin-Oligodendrocyte Glycoprotein)
RN  - 0 (Peptides)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Alleles
MH  - Case-Control Studies
MH  - Female
MH  - Genotype
MH  - HLA Antigens/*genetics
MH  - HLA-DQ alpha-Chains/genetics
MH  - HLA-DQ beta-Chains/genetics
MH  - Haplotypes
MH  - Humans
MH  - Leukocytes, Mononuclear/cytology/drug effects/metabolism
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis, Relapsing-Remitting/genetics/*pathology
MH  - Myelin Basic Protein/chemistry/*metabolism
MH  - Myelin Proteolipid Protein/chemistry/metabolism
MH  - Myelin-Oligodendrocyte Glycoprotein/chemistry/metabolism
MH  - Peptides/pharmacology
MH  - Young Adult
PMC - PMC7766454
OTO - NOTNLM
OT  - HLA class II genotype
OT  - antigen-specific treatment
OT  - multiple sclerosis
OT  - myelin responsiveness
COIS- The authors declare no conflict of interest.
EDAT- 2020/12/23 06:00
MHDA- 2021/06/22 06:00
PMCR- 2020/12/17
CRDT- 2020/12/22 01:03
PHST- 2020/11/14 00:00 [received]
PHST- 2020/12/07 00:00 [revised]
PHST- 2020/12/16 00:00 [accepted]
PHST- 2020/12/22 01:03 [entrez]
PHST- 2020/12/23 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/12/17 00:00 [pmc-release]
AID - cells9122703 [pii]
AID - cells-09-02703 [pii]
AID - 10.3390/cells9122703 [doi]
PST - epublish
SO  - Cells. 2020 Dec 17;9(12):2703. doi: 10.3390/cells9122703.