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The <jats:italic>FCGR2\/3<\/jats:italic> locus, which encodes low-to-medium-affinity Fc\u03b3Rs, contains extensive genetic variation. We hypothesized that genetic variation in the <jats:italic>FCGR2\/3<\/jats:italic> locus influences GBS susceptibility, muscle weakness, outcomes, and the pharmacokinetics of intravenous immunoglobulin (IVIg).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Copy number variation and single nucleotide polymorphisms in the <jats:italic>FCGR2\/3<\/jats:italic> 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\u2009&lt;\u200940 at nadir. The increase in serum IgG one or two weeks after start of IVIg treatment was determined.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>No significant associations were found between genetic variation in the <jats:italic>FCGR2\/3<\/jats:italic> locus and susceptibility to GBS. However, in patients with an antecedent <jats:italic>Campylobacter jejuni<\/jats:italic> infection, a higher frequency of three or more <jats:italic>FCGR3A<\/jats:italic> copies was observed compared to healthy controls (p\u2009=\u20090.023). <jats:italic>FCGR3A<\/jats:italic> copy numbers were also associated with more severe disease (OR\u2009=\u20092.02; 95% CI\u2009=\u20091.00\u20134.12), even after correcting for age and positive <jats:italic>C. jejuni<\/jats:italic> serology. No association was found between <jats:italic>FCGR2\/3<\/jats:italic> 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 <jats:italic>FCGR2\/3<\/jats:italic> locus.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Overall, <jats:italic>FCGR2\/3<\/jats:italic> 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 <jats:italic>C. jejuni<\/jats:italic> infection who more frequently carry a duplication in <jats:italic>FCGR3A<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00415-025-13216-8","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T15:22:02Z","timestamp":1751383322000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic variation of low-to-medium-affinity Fc-gamma receptors in Guillain-Barr\u00e9 syndrome"],"prefix":"10.1007","volume":"272","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3983-9797","authenticated-orcid":false,"given":"Sander J.","family":"van Tilburg","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Selin","family":"Ko\u00e7er","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judy","family":"Geissler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wouter","family":"van Rijs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne P.","family":"Tio-Gillen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael W. 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Selin Ko\u00e7er: Nothing to disclose. Judy Geissler: Nothing to disclose. Wouter van Rijs: Nothing to disclose. Anne Tio-Gillen: Nothing to disclose. Michael Tanck: Nothing to disclose. Willem-Jan Fokkink: Nothing to disclose. Pieter van Doorn: Received research grants from Prinses Beatrix Spierfonds, The Netherlands Organisation for Health Research and Development (ZonMW), Sanquin Blood Supply, Takeda, and Grifols. All grants and fees were paid to his institution. Bart Jacobs: Received research grants for work outside the current study from Baxalta, Grifols, CSL-Behring, Annexon, Hansa Biopharma, Roche, Prinses Beatrix Spierfonds, GBS-CIDP Foundation International, and Horizon 2020 and consultancy fees from Roche for activities outside the current study. All grants and fees were paid to his institution. He is the chair of the Steering Committee of the International GBS Outcome Study (IGOS). Sietse Nagelkerke: Nothing to disclose. Ruth Huizinga: Reports grants from the GBS\/CIDP Foundation International, NIH and the PANDIA collaboration project co-funded by B\u00dcHLMANN Laboratories AG and the PPP Allowance made available by Health\u2009~\u2009Holland, Top Sector Life Sciences & Health, to Prinses Beatrix Spierfonds to stimulate public\u2013private partnerships under project number LSHM23017-SGF.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}],"article-number":"487"}}