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Here, we performed integrated proteomic and phosphoproteomic profiling of peripheral blood mononuclear cells (PBMCs) from a self\u2010established cohort of 130 SLE patients across disease stages and 90 healthy controls, with individual samples pooled into 36 samples for LC\u2010MS\/MS analysis, complemented by publicly available transcriptomic data from 1461 SLE patients. Focusing on membrane\u2010associated proteins, we identified alterations in protein abundance and phosphorylation involving cytoskeletal organization, cell adhesion, and membrane trafficking, with the RHO GTPase cycle consistently enriched in both omic layers. Dynamic multisite phosphorylation of FLNA and increased abundance of FLNB and FNBP1 were observed. Clustering revealed distinct disease\u2010stage\u2010associated patterns involving integrin proteins in SLE in remission (SLE_R) and cytoskeletal and mechanotransduction components in active SLE (SLE_A). OAS3 and IFIT5 showed concordant transcript\u2013protein changes, while interferon\u2010 and NF\u2010\u03baB\u2010related transcriptional programs were implicated. Computational kinase analysis identified disease\u2010stage\u2010associated predicted activity patterns involving PKC, MAPKs, CDKs, and CaM\u2010Ks. Together, these findings provide a multiomics view of membrane\u2010associated molecular alterations associated with disease activity in SLE.<\/jats:p>","DOI":"10.1002\/pmic.70197","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T11:48:27Z","timestamp":1792151307000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Multiomics Profiling Reveals Membrane\u2010Associated Signaling Alterations Associated With Disease Activity in Systemic Lupus Erythematosus"],"prefix":"10.1002","author":[{"given":"Qinxin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Peking University Shenzhen Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Peking University Shenzhen Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Dai","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital School of Medicine Anhui University of Science and Technology  Huainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Peking University Shenzhen Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.2315"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010025\u201002168\u20100"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard\u20102022\u2010223035"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296\u2010022\u201005183\u20104"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1100359"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.7326\/AITC202006020"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.04.018"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2208058119"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.03.038"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01078"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2022.100434"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102018\u2010214502"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.873787"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201009234\u20106"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M111.012625"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200300771"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gpb.2019.09.006"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.2.520"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074\u20107613(00)00077\u20107"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2006.05.006"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00045.2020"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.041019"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1086\/512981"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI170706"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2024.05.006"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.67"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/419029"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2009.12.005"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000014"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021\u20109258(18)71675\u2010X"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02852"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102014\u201001\u2010551820"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010022\u201001259\u20106"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2009.12.001"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103477"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00393\u2010015\u20101619\u20109"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.04.006"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201010102\u20106"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010022\u201000508\u20104"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010cellbio\u2010111315\u2010125341"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01148"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2018.08.002"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2847"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/jxb\/erh012"}],"container-title":["PROTEOMICS"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pmic.70197","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pmic.70197","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pmic.70197","content-type":"unspecified","content-version":"vor","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