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Next-Generation Seq...
Next-Generation Sequencing Identifies Extended HLA Class I and II Haplotypes Associated With Early-Onset and Late-Onset Myasthenia Gravis in Italian, Norwegian, and Swedish Populations
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- Creary, Lisa E. (author)
- Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA; Stanford Blood Ctr, Histocompatibil Immunogenet & Dis Profiling Lab, Palo Alto, CA 94025 USA
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- Gangavarapu, Sridevi (author)
- Stanford Blood Ctr, Histocompatibil Immunogenet & Dis Profiling Lab, Palo Alto, CA 94025 USA
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- Caillier, Stacy J. (author)
- Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA USA
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- Cavalcante, Paola (author)
- Fdn IRCCS Ist Neurol Carlo Besta INCB, Neurol Unit Neuroimmunol & Neuromuscular Dis 4, Milan, Italy
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- Frangiamore, Rita (author)
- Fdn IRCCS Ist Neurol Carlo Besta INCB, Neurol Unit Neuroimmunol & Neuromuscular Dis 4, Milan, Italy
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- Lie, Benedicte A. (author)
- Oslo Univ Hosp, Dept Immunol & Transfus Med, Oslo, Norway; Univ Oslo, Inst Clin Med, Oslo, Norway; Univ Oslo, Dept Med Genet, Oslo, Norway; Oslo Univ Hosp, Dept Med Genet, Oslo, Norway
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- Bengtsson, Mats (author)
- Uppsala universitet,Klinisk immunologi
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- Harbo, Hanne Flinstad (author)
- Oslo Univ Hosp, Dept Neurol, Oslo, Norway; Univ Oslo, Oslo, Norway
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- Brauner, Susanna (author)
- Karolinska Institutet
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- Hollenbach, Jill A. (author)
- Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA USA
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- Oksenberg, Jorge R. (author)
- Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA USA
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- Bernasconi, Pia (author)
- Fdn IRCCS Ist Neurol Carlo Besta INCB, Neurol Unit Neuroimmunol & Neuromuscular Dis 4, Milan, Italy
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- Hatlø Maniaol, Angelina (author)
- Oslo Univ Hosp, Dept Neurol, Oslo, Norway
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- Hammarström, Lennart (author)
- Karolinska Institutet
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- Mantegazza, Renato (author)
- Fdn IRCCS Ist Neurol Carlo Besta INCB, Neurol Unit Neuroimmunol & Neuromuscular Dis 4, Milan, Italy; Fdn IRCCS Ist Neurol Carlo Besta INCB, Dept Clin Res & Innovat, Milan, Italy
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- Fernández-Viña, Marcelo A. (author)
- Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA; Stanford Blood Ctr, Histocompatibil Immunogenet & Dis Profiling Lab, Palo Alto, CA 94025 USA
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(creator_code:org_t)
- 2021-06-07
- 2021
- English.
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In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 12
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Abstract
Subject headings
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- Genetic susceptibility to myasthenia gravis (MG) associates with specific HLA alleles and haplotypes at the class I and II regions in various populations. Previous studies have only examined alleles at a limited number of HLA loci that defined only broad serotypes or alleles defined at the protein sequence level. Consequently, genetic variants in noncoding and untranslated HLA gene segments have not been fully explored but could also be important determinants for MG. To gain further insight into the role of HLA in MG, we applied next-generation sequencing to analyze sequence variation at eleven HLA genes in early-onset (EO) and late-onset (LO) non-thymomatous MG patients positive for the acetylcholine receptor (AChR) antibodies and ethnically matched controls from Italy, Norway, and Sweden. For all three populations, alleles and haplotype blocks present on the ancestral haplotype AH8.1 were associated with risk in AChR-EOMG patients. HLA-B*08:01:01:01 was the dominant risk allele in Italians (OR = 3.28, P = 1.83E−05), Norwegians (OR = 3.52, P = 4.41E−16), and in Swedes HLA-B*08:01 was the primary risk allele (OR = 4.24, P <2.2E-16). Protective alleles and haplotype blocks were identified on the HLA-DRB7, and HLA-DRB13.1 class II haplotypes in Italians and Norwegians, whereas in Swedes HLA-DRB7 exhibited the main protective effect. For AChR-LOMG patients, the HLA-DRB15.1 haplotype and associated alleles were significantly associated with susceptibility in all groups. The HLA-DR13–HLA-DR–HLA-DQ haplotype was associated with protection in all AChR-LOMG groups. This study has confirmed and extended previous findings that the immunogenetic predisposition profiles for EOMG and LOMG are distinct. In addition, the results are consistent with a role for non-coding HLA genetic variants in the pathogenesis of MG.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- myasthenia gravis
- human leukocyte antigen
- next-generation sequencing
- European
- susceptibility
- protection
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Creary, Lisa E.
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Gangavarapu, Sri ...
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Caillier, Stacy ...
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Cavalcante, Paol ...
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Frangiamore, Rit ...
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Lie, Benedicte A ...
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Bengtsson, Mats
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Harbo, Hanne Fli ...
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Brauner, Susanna
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Hollenbach, Jill ...
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Oksenberg, Jorge ...
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Bernasconi, Pia
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Hatlø Maniaol, A ...
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Hammarström, Len ...
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Mantegazza, Rena ...
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Fernández-Viña, ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Frontiers in Imm ...
- By the university
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Uppsala University
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Karolinska Institutet