Immune-mediated neuropathies Research Group
Our group is dedicated to elucidate the pathogenesis of immune-mediated neuropathies, improve diagnostics and predict responses to immunomodulatory treatment.
Immune responses may precipitate a spectrum of severe neuromuscular diseases. Within this spectrum is the Guillain-Barré syndrome (GBS), a post-infectious, life-threatening neuropathy and the most frequent cause of acute neuromuscular paralysis. Chronic forms of immune-mediated neuropathies are multifocal motor neuropathy (MMN) and chronic demyelinating inflammatory polyneuropathy (CIDP). Immune responses are critical in the pathogenesis of all these neuropathies and provide an opportunity for diagnosis and treatment. Through coordination of cohort studies and trials we collected a unique biobank (N>2000; including children) to be used for neuroimmunology research. Moreover we have initiated and coordinate the world-wide International GBS Outcome study (IGOS). Our research is conducted in close collaboration with the departments of Neurology, Medical Microbiology, Virology, Pediatrics, Public Health and Pharmacy.
Antibodies to glycolipids
We identified molecular mimicry and the induction of cross-reactive antibodies to glycolipids as critical events in the pathogenesis of GBS (see Figure). Our group investigates the role of these antibodies in the (normal) immune response to infections and the use as biomarkers for disease activity and prediction of clinical course and outcome. For this purpose we are implementing the novel glycoarray technique in which antibodies to multiple glycolipids can be assessed simultaneously. The Erasmus MC also serves as national reference center for antibody diagnostics in neuroimmunological diseases.
Host-pathogen interactions and B-cell biology
GBS is a typical post-infectious disease, yet it remains unknown why an infection only induces GBS in a small minority of persons. Our goal is to unravel pathogen and host factor interactions that trigger the development of disease. In the case of Campylobacter jejuni, we previously demonstrated that a strong innate response to C. jejuni is associated with GBS. The role of immune responses to viruses is currently explored. In addition, using multicolor flow cytometry we investigate B-cell subsets that are involved in the production of anti-glycolipid antibodies in GBS and anti-(para)nodal antigen antibodies in CIDP.
Figure: Immunopathogenesis of Campylobacter-related GBS (van den Berg et al. Nat Rev Neurol 2014).
Pharmacokinetics of intravenous immunoglobulins
The Erasmus MC research group, in collaboration with the Dutch GBS Study Group, was the first to demonstrate the effectiveness of intravenous immunoglobulins (IVIg) in GBS. At present the first choice treatment for GBS is IVIg. More recently, our group has demonstrated that IgG levels are highly variable in patients with GBS and CIDP and correlate with clinical outcome. Current studies are aimed at modelling IgG levels to optimize treatment of individual patients.
- Preceding infections and other triggers of GBS in children and adults.
- Genetic polymorphisms influencing disease susceptibility, severity and response to treatment.
- Molecular mimicry and immune responses to microbial antigens.
- Biomarkers for disease diagnosis and monitoring, including leukocytes and antibodies to nerve glycolipids.
- Pharmacokinetics and mechanisms of action of intravenous immunoglobulin treatment.
- Bart C. Jacobs, MD, PhD, neurologist-immunologist, Workgroup leader
- Ruth Huizinga, PhD, immunologist and Co-workgroup leader
- Willem Jan Fokkink, PhD student (not on the picture)
- Anne Tio-Gillen, Research Assistant
- Wouter van Rijs, Research Assistant
- Danique Laport, student (not on the picture)
(Check for all publications: Jacobs BC and/or Huizinga R in Pubmed)
Bunschoten C, Jacobs BC, Van den Bergh PYK, Cornblath DR, van Doorn PA.
Progress in diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy.
Brem MD, Jacobs BC, van Rijs W, Fokkink WJR, Tio-Gillen AP, Walgaard C, van Doorn PA, IJspeert H, van der Burg M, Huizinga R.
IVIg-induced plasmablasts in patients with Guillain-Barré syndrome.
Ann Clin Transl Neurol. 2018 Nov 27;6(1):129-143. doi: 10.1002/acn3.687.
Doets AY, Verboon C, van den Berg B, Harbo T, Cornblath DR, Willison HJ, Islam Z, Attarian S, Barroso FA, Bateman K, Benedetti L, van den Bergh P, Casasnovas C, Cavaletti G, Chavada G, Claeys KG, Dardiotis E, Davidson A, van Doorn PA, Feasby TE, Galassi G, Gorson KC, Hartung HP, Hsieh ST, Hughes RAC, Illa I, Islam B, Kusunoki S, Kuwabara S, Lehmann HC, Miller JAL, Mohammad QD, Monges S, Nobile Orazio E, Pardo J, Pereon Y, Rinaldi S, Querol L, Reddel SW, Reisin RC, Shahrizaila N, Sindrup SH, Waqar W, Jacobs BC; IGOS Consortium.
Regional variation of Guillain-Barré syndrome.
Fokkink WR, Walgaard C, Kuitwaard K, Tio-Gillen AP, van Doorn PA, Jacobs BC.
Association of Albumin Levels With Outcome in Intravenous Immunoglobulin-Treated Guillain-Barré Syndrome.
JAMA Neuroldoi: 10.1001/jamaneurol.2016.4480
See also the Editorial comment
Meyer Sauteur PM, Huizinga R, Tio-Gillen AP, Roodbol J, Hoogenboezem T, Jacobs E, van Rijn M, van der Eijk AA, Vink C, de Wit MC, van Rossum AM, Jacobs BC.
Mycoplasma pneumoniae triggering the Guillain-Barré syndrome: A case-control study.
Ann Neurol. doi: 10.1002/ana.24755.
Willison HJ, Jacobs BC and van Doorn PA. Guillain-Barré syndrome.
Lancet 2016 388:717-27.
Huizinga R, van den Berg B, van Rijs W, Tio-Gillen AP, Fokkink WJR, Bakker-Jonges LE, Geleijns K, Samsom JN, van Doorn PA, Laman JD, Jacobs BC.
Innate immunity to Campylobacter jejuni in Guillain-Barré syndrome.
Fokkink WJ, Selman MH, Dortland JR, Durmuş B, Kuitwaard K, Huizinga R, van Rijs W, Tio-Gillen AP, van Doorn PA, Deelder AM, Wuhrer M, Jacobs BC.
IgG Fc N-glycosylation in Guillain-Barré syndrome treated with immunoglobulins.
J Proteome Res. 2014;13:1722-30.
van den Berg B, van der Eijk AA, Pas SD, Hunter JG, Madden RG, Tio-Gillen AP, Dalton HR, Jacobs BC.
Guillain-Barré syndrome associated with preceding hepatitis E virus infection.
Fokke C, van den Berg B, Drenthen J, Walgaard C, van Doorn PA, Jacobs BC.
Diagnosis of Guillain-Barré syndrome and validation of Brighton criteria.
Huizinga R, van Rijs W, Bajramovic JJ, Kuijf ML, Laman JD, Samsom JN, Jacobs BC.
Sialylation of Campylobacter jejuni endotoxin promotes dendritic cell-mediated B cell responses through CD14-dependent production of IFN-β and TNF-α.
J Immunol. 2013;191:5636-45.
Kuijf ML, Samsom JN, van Rijs W, Bax M, Huizinga R, Heikema AP, van Doorn PA, van Belkum A, van Kooyk Y, Burgers PC, Luider TM, Endtz HP, Nieuwenhuis EE, Jacobs BC.
TLR4-mediated sensing of Campylobacter jejuni by dendritic cells is determined by sialylation.
J Immunol. 2010;185:748-55.
Kuitwaard K, de Gelder J, Tio-Gillen AP, Hop WC, van Gelder T, van Toorenenbergen AW, van Doorn PA, Jacobs BC.
Pharmacokinetics of intravenous immunoglobulin and outcome in Guillain-Barré syndrome.
Ann Neurol. 2009;66:597-603.