{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T07:14:45Z","timestamp":1771312485075,"version":"3.50.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"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>Introduction<\/jats:title>\n                    <jats:p>New biomarkers are needed for better stratification and personalized treatment of Systemic Lupus Erythematosus (SLE). Phosphoinositide 3-kinase \u03b4 (PI3K\u03b4) has been implicated in SLE pathogenesis. Here, we investigated whether a subset of SLE patients has increased PI3K\u03b4 activity after T cell activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>T cells were isolated from frozen PBMCs of 108 SLE patients, 19 healthy controls, and one patient with Activated PI3K Delta syndrome (APDS), which provided a benchmark of increased PI3K\u03b4 activity. After 90-minute anti-CD3\/CD28 stimulation, phosphatidylinositol 3,4,5-trisphosphate (PIP3) and phosphatidylinositol 4,5-bisphosphate (PIP2) were measured using high-performance liquid chromatography-mass spectrometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Higher levels of PIP3 (measured as the ratio of PIP3\/PIP2) in stimulated T cells distinguished APDS patient from other subjects providing a useful biomarker of increased PI3K\u03b4 activity. We observed no significant difference in T-cell PIP3 levels between SLE patients and healthy controls. However, a subset of SLE patients (n = 4) exhibited strong upregulation of PIP3 following T-cell stimulation, comparable to that observed in the APDS patient. PIP3 levels in stimulated T cells positively correlated with the frequency of CD4+ T cells and negatively correlated with the frequencies of CD8+, EMRA CD4+, and EMRA CD8+ T cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We describe the range of variation of PI3K\u03b4 activity in T cells from a large cohort of patients with SLE and from healthy subjects. Our findings suggest that increased PI3K\u03b4 activity is not associated with SLE in general, although some SLE patients exhibit a particularly strong upregulation of PIP3 levels after T-cell stimulation. This subgroup of SLE patients warrants further investigation given the promising effect of PI3K\u03b4 inhibitors in restoring normal immune regulation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1745692","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T06:34:05Z","timestamp":1771310045000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Phosphoinositide 3-kinase \u03b4 activity in patients with systemic lupus erythematosus"],"prefix":"10.3389","volume":"17","author":[{"given":"Elham Sadat","family":"Mirfazeli","sequence":"first","affiliation":[{"name":"Molecular Cell Biology and Immunology, Amsterdam UMC Location Vrije Universiteit Amsterdam","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Institute for Immunology and Infectious Diseases","place":["Amsterdam, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shalmalee","family":"Kharkar","sequence":"additional","affiliation":[{"name":"Molecular Cell Biology and Immunology, Amsterdam UMC Location Vrije Universiteit Amsterdam","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Institute for Immunology and Infectious Diseases","place":["Amsterdam, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel W. P.","family":"Tsang-A-Sjoe","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology Amsterdam UMC","place":["Amsterdam, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier","family":"Papapietro","sequence":"additional","affiliation":[{"name":"Molecular Cell Biology and Immunology, Amsterdam UMC Location Vrije Universiteit Amsterdam","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Institute for Immunology and Infectious Diseases","place":["Amsterdam, Netherlands"]},{"name":"Department of Medicine, University of Cambridge","place":["Cambridge, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izabella","family":"Niewczas","sequence":"additional","affiliation":[{"name":"Babraham Institute","place":["Cambridge, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agner R.","family":"Parra Sanchez","sequence":"additional","affiliation":[{"name":"Amsterdam Institute for Immunology and Infectious Diseases","place":["Amsterdam, Netherlands"]},{"name":"Department of Rheumatology and Clinical Immunology Amsterdam UMC","place":["Amsterdam, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Chandra","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge","place":["Cambridge, United Kingdom"]},{"name":"Department of Clinical Immunology, Cambridge University Hospitals NHS Foundation Trust","place":["Cambridge, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Okkenhaug","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Cambridge","place":["Cambridge, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene E. 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