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Higher frequencies of HLA DQB1*05:01 and anti-glycosphingolipid antibodies in a cluster of severe Guillain–Barré syndrome

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Abstract

Few regional and seasonal Guillain–Barré syndrome (GBS) clusters have been reported so far. It is unknown whether patients suffering from sporadic GBS differ from GBS clusters with respect to clinical and paraclinical parameters, HLA association and antibody response to glycosphingolipids and Campylobacter jejuni (Cj). We examined 40 consecutive patients with GBS from the greater Munich area in Germany with 14 of those admitted within a period of 3 months in fall 2010 defining a cluster of GBS. Sequencing-based HLA typing of the HLA genes DRB1, DQB1, and DPB1 was performed, and ELISA for anti-glycosphingolipid antibodies was carried out. Clinical and paraclinical findings (Cj seroreactivity, cerebrospinal fluid parameters, and electrophysiology) were obtained and analyzed. GBS cluster patients were characterized by a more severe clinical phenotype with more patients requiring mechanical ventilation and higher frequencies of autoantibodies against sulfatide, GalC and certain ganglioside epitopes (54 %) as compared to sporadic GBS cases (13 %, p = 0.017). Cj seropositivity tended to be higher within GBS cluster patients (69 %) as compared to sporadic cases (46 %, p = 0.155). We noted higher frequencies of HLA class II allele DQB1*05:01 in the cluster cohort (23 %) as compared to sporadic GBS patients (3 %, p = 0.019). Cluster of severe GBS was defined by higher frequencies of autoantibodies against glycosphingolipids. HLA class II allele DQB1*05:01 might contribute to clinical worsening in the cluster patients.

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Acknowledgments

We thank Nadine Miksch and Heike Mating for excellent technical assistance.

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Authors and Affiliations

  1. Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

    L. Schirmer, V. Loleit, V. Grummel, A. Berthele & Bernhard Hemmer

  2. MRC Centre for Neuromuscular Diseases and Neuroimmunology and CSF Laboratory, National Hospital for Neurology, London, UK

    V. Worthington, N. Lakdawala, D. Grant & M. P. Lunn

  3. DKMS German Bone Marrow Center, Tübingen, Germany

    U. Solloch, A. H. Schmidt & J. Sauter

  4. DKMS Life Science Lab, Dresden, Germany

    R. Wassmuth & A. H. Schmidt

  5. Department of Quality Management, University Hospital Düsseldorf, Düsseldorf, Germany

    R. Wassmuth

  6. Institute for Medical Microbiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

    F. Gebhardt

  7. Max Planck Institute of Psychiatry, Munich, Germany

    T. F. M. Andlauer

  8. Munich Cluster for Systems Neurology (SyNergy), Munich, Germany

    T. F. M. Andlauer & Bernhard Hemmer

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  1. L. Schirmer
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Correspondence to Bernhard Hemmer.

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Financial disclosure

LS was supported by intramural funding of the medical faculty of the Technische Universität München. BH was supported by grants from the German Research Foundation (SFB-TR128) and the German Ministry for Education and Research (German Competence Network Multiple Sclerosis, Control-MS, 01GI0917).

Conflicts of interest

LS has received travel support from Genzyme Corporation. VW, US, VL, VG, NL, DG, RW, AHS, FG, TFMA, JS and MPL report no disclosures relevant to the manuscript. AB has received travel support and personal compensations from Biogen, Bayer Healthcare, Teva, Sanofi, Merck Serono and Novartis and research support from Bayer Healthcare. BH has served on scientific advisory boards for F. Hoffmann-La Roche Ltd., Novartis, Bayer Healthcare, Merck Serono, Biogen, Chugai Pharmaceuticals, and Genentech; serves on the international advisory board of JAMA Neurology, Multiple Sclerosis Journal, and Experimental Neurology; has received speaker honoraria from Bayer Healthcare, Novartis, Biogen, Merck Serono, and F. Hoffmann-La Roche Ltd.; has received research support from Five Prime, Chugai Pharmaceuticals and F. Hoffmann-La Roche Ltd. LS and BH have filed a patent for the detection of antibodies against KIR4.1 in a subpopulation of patients with MS. BH has filed a patent for genetic determinants of neutralizing antibodies to interferon-beta.

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The study was approved by the ethics commission of the Klinikum rechts der Isar, Technical University of Munich.

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Schirmer, L., Worthington, V., Solloch, U. et al. Higher frequencies of HLA DQB1*05:01 and anti-glycosphingolipid antibodies in a cluster of severe Guillain–Barré syndrome. J Neurol 263, 2105–2113 (2016). https://doi.org/10.1007/s00415-016-8237-6

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