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A hierarchy is apparent with early classical pathway components, particularly C1q, exerting the greatest influence. Understanding the mechanisms underlying the protective function(s) of complement remains an important challenge for the future and has implications for the use of complement therapy in SLE. We review recent advances in the field and give a new perspective on the complement conundrum in SLE.<\/jats:p>","DOI":"10.1002\/eji.202350918","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T04:17:06Z","timestamp":1713327426000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Canonical and noncanonical functions of complement in systemic lupus erythematosus"],"prefix":"10.1002","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1153-0192","authenticated-orcid":false,"given":"Matthew C","family":"Pickering","sequence":"first","affiliation":[{"name":"Department of Immunology and Inflammation Centre for Inflammatory Disease Imperial College London  London United Kingdom of Great Britain and Northern Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1458-3791","authenticated-orcid":false,"given":"Marina","family":"Botto","sequence":"additional","affiliation":[{"name":"Department of Immunology and Inflammation Centre for Inflammatory Disease Imperial College London  London United Kingdom of Great Britain and Northern Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(01)76021-X"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2012.08.004"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.22.012703.104549"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2015.05.001"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2003.10.009"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00052"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.138.4.1150"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.12.7496"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0598-56"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.3.359"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.4.1317"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-010-0530-8"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.12.2313"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/75963"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2015.12.017"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0212099"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3206"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200425497"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00402"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2019.10.008"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/1753425909339815"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.3A0614-278R"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24852"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001731"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102797"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2017.05.025"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2310666120"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.158.10.4525"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao4555"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.6.815"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20745"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22654"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22312-y"},{"key":"e_1_2_9_35_1","unstructured":"National Institute for Health and Care Excellence Belimumab for treating active autoantibody\u2010positive systemic lupus erythematosus \u2010 Technology appraisal guidance [TA752]\u2010https:\/\/www.nice.org.uk\/guidance\/ta7522021."},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.5.2734"},{"key":"e_1_2_9_37_1","article-title":"2021 DORIS definition of remission in SLE: final recommendations from an international task force","volume":"8","author":"Vollenhoven R. 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