{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:25:11Z","timestamp":1792650311401,"version":"4.5.0"},"reference-count":90,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T00:00:00Z","timestamp":1782518400000},"content-version":"vor","delay-in-days":26,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The V158F polymorphism found in the human Fc receptor CD16a (also known as Fc\u03b3RIIIa) is thought to influence autoimmune disorders and responses to IgG-based therapies. V158F is known to influence the IgG affinity, and thereby triggering of the CD16a receptor expressed on various immune cells. In contrast to CD16 triggering by opsonized IgG, the mechanistic details of its interaction with soluble circulating IgG immune complexes (ICs) remain poorly understood. In this study we aimed to clarify the functional impact of the CD16a-V158F polymorphism in the context of IC-mediated diseases. We generated BW5147 reporter cells for both human CD16a V158F polymorphic variants. Using synthetic and disease-associated soluble IgG ICs, we assessed their respective functional responses, which were further validated using primary human NK cells. While both reporter cell variants bound ICs, the CD16aV but not the CD16aF reporter cells exhibited functional response to soluble ICs. This functional dichotomy was further confirmed in primary CD16+ human NK cells. We provide evidence for an intrinsic difference between V158F polymorphic variants of human CD16a in their responsiveness to soluble ICs, extending beyond the previously reported distinctions of low- and high-affinity binding. Future studies investigating genotype-dependent clinical-immunological differences could enhance our understanding of the pathophysiology in IC-mediated diseases and pave the way for potential individualized treatment strategies.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag160","type":"journal-article","created":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T01:22:21Z","timestamp":1782523341000},"source":"Crossref","is-referenced-by-count":1,"title":["The V158F polymorphism in human Fc\u03b3RIIIa\/CD16a defines opposing receptor responses when interacting with soluble immune complexes"],"prefix":"10.1093","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2116-5973","authenticated-orcid":false,"given":"Nicolas Manuel","family":"Eckert","sequence":"first","affiliation":[{"name":"Institute of Virology, Medical Center\u2014University of Freiburg , Freiburg,","place":["Germany"]},{"name":"Faculty of Medicine, University of Freiburg , Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Kolb","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical Center\u2014University of Freiburg , Freiburg,","place":["Germany"]},{"name":"Faculty of Medicine, University of Freiburg , Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Lerch","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical Center\u2014University of Freiburg , Freiburg,","place":["Germany"]},{"name":"Faculty of Medicine, University of Freiburg , Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard Edmund","family":"Voll","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Freiburg , Freiburg,","place":["Germany"]},{"name":"Department of Rheumatology and Clinical Immunology, Medical Center\u2014University of Freiburg , Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maike","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Freiburg , Freiburg,","place":["Germany"]},{"name":"Department of Medicine II, Medical Center\u2014University of Freiburg , Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Puchhammer-St\u00f6ckl","sequence":"additional","affiliation":[{"name":"Center for Virology, Medical University of Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannes","family":"Vietzen","sequence":"additional","affiliation":[{"name":"Center for Virology, Medical University of Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Falcone","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical 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