{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:40:59Z","timestamp":1793047259507,"version":"4.5.0"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"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>Hematologic immune dysregulation (H-ID) \u2013 including autoimmune cytopenia (AIC), lymphoproliferation (LPD), and hemophagocytic lymphohistiocytosis (HLH) \u2013 is a potentially life-threatening manifestation of inborn errors of immunity (IEI). Despite the availability of targeted therapies, its management remains challenging, with no standardized treatment strategies established.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the efficacy and safety of the available treatments for H-ID, with a specific focus on the treatment indications and outcome differences between targeted versus non-targeted therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicentric retrospective study included 116 patients with IEI and H-ID across Italian tertiary care centers. Data included treatment indications, response rate, and incidence of adverse events (AEs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We included patients with autoimmune lymphoproliferative immunodeficiencies (ALPID, 37.1%), humoral immunodeficiencies (31%), syndromic IEI (8.6%), and combined immunodeficiencies (8.6%). H-ID consisted of AIC (67.2%), LPD (71.6%), and HLH (9.5%). 85.3% of patients received treatment, including on-demand therapies (37.9%), long-term treatments (LTT, 84.8%), and hematopoietic stem-cell transplantation (HSCT; 9.1%). LTT included sirolimus (42.9%), mycophenolate mofetil (34.5%), rituximab (29.8%), and targeted therapies (17.9%). Sirolimus showed a higher complete response (CR) rate (61.1%), especially in ALPID patients and those with lymphoproliferation (72%). CR rate was significantly higher in patients receiving targeted therapies (80% vs 43.4%,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.05). AEs were reported in 13.3% of cases, leading to drug withdrawal in 3.6%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The indications for LTT and HSCT in H-ID are still heterogeneous. Response rates are variable and influenced by the underlying diagnosis. Targeted therapies are associated with an improved response, the suboptimal molecular diagnosis rate currently limits their use.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1854044","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T04:24:55Z","timestamp":1785126295000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Treating hematologic immune dysregulation in inborn errors of immunity: a real-life multicenter study"],"prefix":"10.3389","volume":"17","author":[{"given":"Giorgio","family":"Costagliola","sequence":"first","affiliation":[{"name":"Section of Pediatric Hematology and Oncology, Azienda Ospedaliero-Universitaria Pisana","place":["Pisa, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Consonni","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio,\u201d University of Florence","place":["Florence, Italy"]},{"name":"Department of Clinical and Experimental Sciences, University of Brescia","place":["Brescia, Italy"]},{"name":"Pediatric Immunology Unit, Pediatrics Clinic, ASST Spedali Civili di Brescia","place":["Brescia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Castagnoli","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia","place":["Pavia, Italy"]},{"name":"Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo","place":["Pavia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayla","family":"Sgrulletti","sequence":"additional","affiliation":[{"name":"Pediatric Immunopathology and Allergology Unit, Policlinico Tor Vergata, University of Rome Tor Vergata","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Gambineri","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology\/Hematology, Meyer Children\u2019s Hospital IRCCS","place":["Florence, Italy"]},{"name":"Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence","place":["Florence, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuliana","family":"Giardino","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Pediatric Section, University of Naples Federico II","place":["Naples, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Cavone","sequence":"additional","affiliation":[{"name":"Section of Pediatric Hematology and Oncology, Azienda Ospedaliero-Universitaria Pisana","place":["Pisa, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Montin","sequence":"additional","affiliation":[{"name":"Division of Pediatric Immunology and Rheumatology, Department of Public Health and Pediatrics Sciences, Regina Margherita Children\u2019s Hospital, University of Turin","place":["Turin, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Conti","sequence":"additional","affiliation":[{"name":"Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna","place":["Bologna, Italy"]},{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna","place":["Bologna, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baldassarre","family":"Martire","sequence":"additional","affiliation":[{"name":"Pediatrics and Neonatology Unit, Maternal-Infant Department, \u201cMonsignor A. 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