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January 20, 2021 article Open access Aachen paper

High-resolution mapping identifies HLA class II associations with multifocal motor neuropathy

Neurobiology of Aging, vol. 101, pp. 79–84

DOI: 10.1016/j.neurobiolaging.2021.01.014 Full text (OA) OpenAlex

Abstract

OBJECTIVE: To gain further insight in the immunopathology underlying multifocal motor neuropathy (MMN) by exploring the association between MMN and the human leukocyte antigen (HLA) class II DRB1, DQB1, and DQA loci in depth and by correlating associated haplotypes to detailed clinical and anti-ganglioside antibody data. METHODS: We performed high-resolution HLA-class II typing for the DRB1, DQB1, and DQA1 loci in 126 well-characterized MMN patients and assessed disease associations with haplotypes. We used a cohort of 1305 random individuals as a reference for haplotype distribution in the Dutch population. RESULTS: The DRB1*15:01-DQB1*06:02 haplotype (OR 1.6 [95% CI 1.1-2.2], p < 0.05) and the DRB1*12:01-DQB1*03:01 haplotype (OR 2.7 [95% CI 1.2-5.5], p < 0.05) were more frequent in patients with MMN than in controls. These haplotypes were not associated with disease course, response to treatment or anti-ganglioside antibodies. CONCLUSIONS: MMN is associated with the DRB1*15:01-DQB1*06:02 and DRB1*12:01-DQB1*03:01 haplotypes. These HLA molecules or gene variants in their immediate vicinity may promote the specific inflammatory processes underlying MMN.

Authors 9

  1. Jeroen W. Bos

    University Medical Center Utrecht

    Affiliation as printed

    UMC Utrecht Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, Utrecht, the Netherlands

  2. Henny G. Otten

    University Medical Center Utrecht

    Affiliation as printed

    Department of Immunology, University Medical Center Utrecht, Utrecht, the Netherlands

  3. Ingrid J.T. Herraets

    University Medical Center Utrecht

    Affiliation as printed

    UMC Utrecht Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, Utrecht, the Netherlands

  4. Hendrik Stephan Goedee

    University Medical Center Utrecht

    Affiliation as printed

    UMC Utrecht Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, Utrecht, the Netherlands

  5. Elisabeth A. Cats

    University Medical Center Utrecht

    Affiliation as printed

    UMC Utrecht Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, Utrecht, the Netherlands

  6. Talitha de Hoop

    University Medical Center Utrecht

    Affiliation as printed

    Department of Immunology, University Medical Center Utrecht, Utrecht, the Netherlands

  7. Willem Verduijn Aachen Department of Immunohematology and Blood Transfusion

    Leiden University · Leiden University Medical Center

    Affiliation as printed

    Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, the Netherlands

  8. W. Ludo van der Pol

    University Medical Center Utrecht

    Affiliation as printed

    UMC Utrecht Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, Utrecht, the Netherlands

  9. Leonard H. van den Berg corresponding

    University Medical Center Utrecht

    Affiliation as printed

    UMC Utrecht Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, Utrecht, the Netherlands. Electronic address: l.h.vandenberg@umcutrecht.nl

    UMC Utrecht Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, Utrecht, the Netherlands

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References 28