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Introduction <p>Fc-gamma receptors (FcγRs) are important for the effector functions of immunoglobulin G (IgG) and are therefore expected to play a role in the pathophysiology of Guillain-Barré syndrome (GBS). The <i>FCGR2/3</i> locus, which encodes low-to-medium-affinity FcγRs, contains extensive genetic variation. We hypothesized that genetic variation in the <i>FCGR2/3</i> locus influences GBS susceptibility, muscle weakness, outcomes, and the pharmacokinetics of intravenous immunoglobulin (IVIg).</p> Methods <p>Copy number variation and single nucleotide polymorphisms in the <i>FCGR2/3</i> locus were studied using multiplex ligation-dependent probe amplification (MLPA). The study cohort consisted of 467 GBS patients and 919 healthy controls of European descent. Severe weakness was defined as an MRC sum score &lt; 40 at nadir. The increase in serum IgG one or two weeks after start of IVIg treatment was determined.</p> Results <p>No significant associations were found between genetic variation in the <i>FCGR2/3</i> locus and susceptibility to GBS. However, in patients with an antecedent <i>Campylobacter jejuni</i> infection, a higher frequency of three or more <i>FCGR3A</i> copies was observed compared to healthy controls (p = 0.023). <i>FCGR3A</i> copy numbers were also associated with more severe disease (OR = 2.02; 95% CI = 1.00–4.12), even after correcting for age and positive <i>C. jejuni</i> serology. No association was found between <i>FCGR2/3</i> variants and the ability to walk unaided in time-to-event analyses. In addition, the pharmacokinetics of IVIg were not affected by genetic variation in the <i>FCGR2/3</i> locus.</p> Conclusion <p>Overall, <i>FCGR2/3</i> polymorphisms are not associated with susceptibility to GBS or response to IVIg treatment. However, associations may exist in specific subgroups, as demonstrated in patients with a preceding <i>C. jejuni</i> infection who more frequently carry a duplication in <i>FCGR3A</i>.</p>

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Genetic variation of low-to-medium-affinity Fc-gamma receptors in Guillain-Barré syndrome

  • 期刊论文

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  • 发表日期：

    2025年7月1日

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  • Sander J. van Tilburg,
  • Selin Koçer,
  • Judy Geissler,
  • Wouter van Rijs,
  • Anne P. Tio-Gillen,
  • Michael W. T. Tanck,
  • Willem-Jan R. Fokkink,
  • Pieter A. van Doorn,
  • Bart C. Jacobs,
  • Sietse Q. Nagelkerke,
  • Ruth Huizinga

摘要

Introduction

Fc-gamma receptors (FcγRs) are important for the effector functions of immunoglobulin G (IgG) and are therefore expected to play a role in the pathophysiology of Guillain-Barré syndrome (GBS). The FCGR2/3 locus, which encodes low-to-medium-affinity FcγRs, contains extensive genetic variation. We hypothesized that genetic variation in the FCGR2/3 locus influences GBS susceptibility, muscle weakness, outcomes, and the pharmacokinetics of intravenous immunoglobulin (IVIg).

Methods

Copy number variation and single nucleotide polymorphisms in the FCGR2/3 locus were studied using multiplex ligation-dependent probe amplification (MLPA). The study cohort consisted of 467 GBS patients and 919 healthy controls of European descent. Severe weakness was defined as an MRC sum score < 40 at nadir. The increase in serum IgG one or two weeks after start of IVIg treatment was determined.

Results

No significant associations were found between genetic variation in the FCGR2/3 locus and susceptibility to GBS. However, in patients with an antecedent Campylobacter jejuni infection, a higher frequency of three or more FCGR3A copies was observed compared to healthy controls (p = 0.023). FCGR3A copy numbers were also associated with more severe disease (OR = 2.02; 95% CI = 1.00–4.12), even after correcting for age and positive C. jejuni serology. No association was found between FCGR2/3 variants and the ability to walk unaided in time-to-event analyses. In addition, the pharmacokinetics of IVIg were not affected by genetic variation in the FCGR2/3 locus.

Conclusion

Overall, FCGR2/3 polymorphisms are not associated with susceptibility to GBS or response to IVIg treatment. However, associations may exist in specific subgroups, as demonstrated in patients with a preceding C. jejuni infection who more frequently carry a duplication in FCGR3A.