{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T21:10:12Z","timestamp":1789161012106,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T00:00:00Z","timestamp":1772841600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T00:00:00Z","timestamp":1772841600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["ZCLQN25H1002"],"award-info":[{"award-number":["ZCLQN25H1002"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100022963","name":"Key Research and Development Program of Zhejiang Province","doi-asserted-by":"publisher","award":["2023C03032"],"award-info":[{"award-number":["2023C03032"]}],"id":[{"id":"10.13039\/100022963","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp;amp; Rheumatology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      This study aimed to investigate the mechanisms of immune dysregulation in a pediatric patient with monogenic lupus driven by\n                      <jats:italic>IKZF1<\/jats:italic>\n                      haploinsufficiency.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Peripheral immune cells from a patient with\n                      <jats:italic>IKZF1<\/jats:italic>\n                      haploinsufficiency, patients with lupus with no currently known genetic mutations, and healthy controls were analyzed using single\u2010cell RNA sequencing. Bioinformatic analyses, including pseudotime trajectory and network reconstruction, were performed. Activation of the type I interferon (IFN) pathway was evaluated by measuring serum cytokine levels, IFN signatures, and the phosphorylation status of JAK and STAT.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The patient with\n                      <jats:italic>IKZF1<\/jats:italic>\n                      haploinsufficiency exhibited notable B cell and T cell dysregulation, with nearly total absence of Breg cells and an increased percentage of naive CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells. Pseudotime analysis in this patient suggested simplified B cell differentiation trajectories with arrested maturation and naive\u2010like cell resurgence. Weighted gene coexpression network analysis identified a lupus\u2010linked gene module (\n                      <jats:italic>IKZF1<\/jats:italic>\n                      ,\n                      <jats:italic>DUSP1<\/jats:italic>\n                      ,\n                      <jats:italic>JUN<\/jats:italic>\n                      ,\n                      <jats:italic>FOS<\/jats:italic>\n                      ), with inferred networks suggesting compensatory stress circuits (\n                      <jats:italic>DUSP1<\/jats:italic>\n                      ,\n                      <jats:italic>DDX17<\/jats:italic>\n                      ). Overactivation of the IFN\/JAK\/STAT signaling pathway was observed in the patient with\n                      <jats:italic>IKZF1<\/jats:italic>\n                      haploinsufficiency. Given persistent thrombocytopenia, baricitinib combined with mycophenolate mofetil was administered based on these findings. Her platelet count returned to normal in a month after combination therapy with baricitinib.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>IKZF1<\/jats:italic>\n                      haploinsufficiency disrupted lymphocyte homeostasis, especially of Breg cells and naive CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells, highlighting these as key\n                      <jats:italic>IKZF1<\/jats:italic>\n                      functional targets. A phenotype\u2010 and single cell\u2013based approach may offer a pathway toward more precise diagnosis and personalized treatment strategies for monogenic lupus.\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art70017-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70017","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T08:00:50Z","timestamp":1765785650000},"page":"1231-1244","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Single\u2010Cell\n                    <scp>RNA<\/scp>\n                    Sequencing Informs Precision Targeting of Monogenic Lupus Associated With\n                    <scp>\n                      <i>IKZF1<\/i>\n                    <\/scp>\n                    Haploinsufficiency"],"prefix":"10.1002","volume":"78","author":[{"given":"Qi","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Immunology, and Allergy, Children's Hospital Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents' Health and Diseases  Hangzhou 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