{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:49:08Z","timestamp":1780318148304,"version":"3.54.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Anti-\u03b22glycoprotein I (\u03b22GPI) antibodies are the hallmark of the antiphospholipid syndrome (APS). \u03b22GPI consists of five domains, DI-DV. While DI is the primary target, the clinical relevance of antibodies against other domains remains uncertain. We analyzed two large anti-\u03b22GPI IgG positive cohorts, to investigate whether different domain binding affects anti-\u03b22GPI IgG assay testing and APS diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The presence of anti-DI and anti-DIV\/DV antibodies (by chemiluminescence (CLIA) and in-house ELISA, respectively) was searched in an APS ACTION (n.191) and Italian validation (n.105) cohorts. In the latter, we detected anti-\u03b22GPI IgG reactivity by four assays (in-house and commercial ELISA, CLIA, and fluorescence enzyme immunoassay), and used a modified anti-\u03b22GPI IgG in-house ELISA with recombinant single-domain-lacking \u03b22GPI variants to evaluate domain-dependent reactivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We confirmed anti-DI, anti-DIV\/DV \u03b22GPI IgG direct reactivity in classified and non-classifiable APS in the two cohorts, and found anti-DI\/anti-DIV\/DV double negative (38\/191, 29\/105) and anti-DIV\/DV single-positive (6\/191, 9\/105) samples. Anti-\u03b22GPI IgG discordant samples by the four methods had the highest presence of anti-DIV\/DV single-positives and anti-DI\/anti-DIV\/DV double-negatives, compared to four-method concordant samples: 16% vs 2% and 45% vs 11% (p &amp;lt;0.0001), respectively. The single-domain molecule-based assay showed that the APS serum samples depended mainly on DI, DV, and DII, slightly on DIV, and not at all on DIII.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Serum IgG from both classified and non-classifiable APS may react with other \u03b22GPI domains than DI and DIV-V. Anti-\u03b22GPI domain selectivity can explain discordant results among diagnostic assays.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1809192","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T05:35:38Z","timestamp":1777613738000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti-\u03b22GPI IgG display a broad reactivity against different \u03b22GPI domains beyond domain 1: results from the APS ACTION and multi-center Italian cohorts"],"prefix":"10.3389","volume":"17","author":[{"given":"Claudia","family":"Grossi","sequence":"first","affiliation":[{"name":"Laboratory of Immuno-Rheumatology, IRCCS Istituto Auxologico Italiano","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Bodio","sequence":"additional","affiliation":[{"name":"Laboratory of Immuno-Rheumatology, IRCCS Istituto Auxologico Italiano","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Edward A. 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