{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T23:31:09Z","timestamp":1780097469132,"version":"3.54.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Gusu Health Talent Plan of Suzhou","award":["2022194"],"award-info":[{"award-number":["2022194"]}]},{"name":"Gusu Health Talent Plan of Suzhou","award":["GSWS2022043"],"award-info":[{"award-number":["GSWS2022043"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aimed to explore the association of low complement items with the performance of the systemic lupus erythematosus (SLE) classification criteria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study included 352 patients with SLE and 385 individuals with positive antinuclear antibodies with other diseases. The performance of the Systemic Lupus International Collaborating Clinics (SLICC)-2012, European League Against Rheumatism and American College of Rheumatology (EULAR\/ACR)-2019, and SLE Risk Probability Index (SLERPI) were compared before and after excluding the low complement item.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The exclusion of the low complement item decreased the sensitivity and increased the specificity of SLICC-2012 and EULAR\/ACR-2019, whereas SLERPI demonstrated stable classification performance in classifying patients with and without SLE. SLICC-2012 exhibited the highest sensitivity in identifying patients with SLE with hypocomplementemia (99.0%; 95% confidence interval [CI]: 97.2\u201399.8%), followed by SLERPI (98.4%; 95% CI: 96.3\u201399.5%) and EULAR\/ACR-2019 (97.7%; 95% CI: 95.4\u201399.1%). After excluding the low complement item, the sensitivities decreased to 93.0% (89.5\u201395.5%) for SLICC-2012, 97.5% (86.8\u201399.9%) for SLERPI, and 93.3% (90.0\u201395.8%) for EULAR\/ACR-2019. SLICC-2012, EULAR\/ACR-2019, and SLERPI identified 16, 17, and 21 patients with SLE with hypocomplementemia before clinical diagnosis, decreasing to 10, 16, and 20 cases after excluding the low complement item. Further, patients with SLE with both low C3 and C4 levels demonstrated shorter disease duration, higher acute cutaneous lupus prevalence, nonscarring alopecia, and increased positivity rates for anti-DNA antibodies, antiphospholipid antibodies, and direct Coombs\u2019 tests compared with those with low C3 or C4 levels. The SLE group with low C3 and C4 levels demonstrated significantly higher total scores than the SLE group with low C3 or C4 levels in all three classification criteria, and this significance persisted even after excluding the low complement item.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The low complement item strongly improved the sensitivity and early classification capacity of SLICC-2012 while minimally influencing SLERPI. Furthermore, higher weights assigned to combined low C3 and C4 levels in EULAR\/ACR-2019 appear clinically justified.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2025.1695383","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T06:34:30Z","timestamp":1765521270000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Low complement items play different roles on the classification performance of SLICC-2012, EULAR\/ACR-2019, and SLERPI"],"prefix":"10.3389","volume":"12","author":[{"given":"Shanshan","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxue","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leixi","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1016\/S0140-6736(24)02380-8","article-title":"Therapies for systemic lupus erythematosus","volume":"404","author":"de Fremont","year":"2024","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1146\/annurev.immunol.22.012703.104549","article-title":"The role of complement in the development of systemic lupus erythematosus","volume":"22","author":"Manderson","year":"2004","journal-title":"Annu Rev Immunol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.jaut.2014.01.004","article-title":"Diagnostic criteria for systemic lupus erythematosus: a critical review","author":"Yu","year":"2014","journal-title":"J Autoimmun"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e000988","DOI":"10.1136\/lupus-2023-000988","article-title":"Systemic lupus erythematosus risk probability index: ready for routine use? Results from a Chinese cohort","volume":"10","author":"Zhang","year":"2023","journal-title":"Lupus Sci Med"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e000718","DOI":"10.1136\/lupus-2022-000718","article-title":"Utility of the ACR- 1997, SLICC- 2012 and EULAR\/ACR-2019 classification criteria for systemic lupus erythematosus: a single-Centre retrospective study","volume":"9","author":"Lu","year":"2022","journal-title":"Lupus Sci Med"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/j.rdc.2021.04.011","article-title":"Systemic lupus erythematosus classification and diagnosis","volume":"47","author":"Aringer","year":"2021","journal-title":"Rheum Dis Clin N Am"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1002\/art.1780400928","article-title":"Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus","volume":"40","author":"Hochberg","year":"1997","journal-title":"Arthritis Rheum"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1136\/annrheumdis-2020-219069","article-title":"Lupus or not? SLE risk probability index (SLERPI): a simple, clinician-friendly machine learning-based model to assist the diagnosis of systemic lupus erythematosus","volume":"80","author":"Adamichou","year":"2021","journal-title":"Ann Rheum Dis"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1002\/art.40930","article-title":"2019 European league against rheumatism\/American College of Rheumatology Classification Criteria for systemic lupus erythematosus","volume":"71","author":"Aringer","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"2677","DOI":"10.1002\/art.34473","article-title":"Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus","volume":"64","author":"Petri","year":"2012","journal-title":"Arthritis Rheum"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2424","DOI":"10.1093\/rheumatology\/keab807","article-title":"Population-based incidence and time to classification of systemic lupus erythematosus by three different classification criteria: a lupus Midwest network (LUMEN) study","volume":"61","author":"Duarte-Garcia","year":"2022","journal-title":"Rheumatology (Oxford)"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"102845","DOI":"10.1016\/j.jaut.2022.102845","article-title":"Advances in SLE classification criteria","volume":"132","author":"Aringer","year":"2022","journal-title":"J Autoimmun"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1191\/0961203304lu1080oa","article-title":"Hypocomplementemia in systemic lupus erythematosus and primary antiphospholipid syndrome: prevalence and clinical significance in 667 patients","volume":"13","author":"Ramos-Casals","year":"2004","journal-title":"Lupus"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1016\/j.semarthrit.2020.06.009","article-title":"The clinical and serological associations of hypocomplementemia in a longitudinal sle cohort","volume":"50","author":"Durcan","year":"2020","journal-title":"Semin Arthritis Rheum"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s42358-022-00283-y","article-title":"The impact of normal serum complement levels on the disease classification and clinical characteristics in systemic lupus erythematosus","volume":"62","author":"Takamatsu","year":"2022","journal-title":"Adv Rheumatol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.1177\/0961203318804892","article-title":"Progressive reduction of serum complement levels: a risk factor for relapse in patients with hypocomplementemia in systemic lupus erythematosus","volume":"27","author":"Miyawaki","year":"2018","journal-title":"Lupus"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1136\/ard.45.5.359","article-title":"Predictive value of complement profiles and anti-dsDNA in systemic lupus erythematosus","volume":"45","author":"Swaak","year":"1986","journal-title":"Ann Rheum Dis"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1007\/s12026-012-8345-z","article-title":"Linking complement and anti-dsDNA antibodies in the pathogenesis of systemic lupus erythematosus","volume":"55","author":"Giles","year":"2013","journal-title":"Immunol Res"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"8051972","DOI":"10.1155\/2018\/8051972","article-title":"Hypocomplementemia as a risk factor for organ damage accrual in patients with systemic lupus erythematosus","volume":"2018","author":"Raymond","year":"2018","journal-title":"J Immunol Res"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1177\/09612033241238053","article-title":"Comparison of the SLE risk probability index (SLERPI) scale against the European league against rheumatism\/American College of Rheumatology (ACR\/EULAR) and systemic lupus international collaborating clinics (SLICC) criteria","volume":"33","author":"Castaneda-Gonzalez","year":"2024","journal-title":"Lupus"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.trsl.2022.03.005","article-title":"Intertwined pathways of complement activation command the pathogenesis of lupus nephritis","volume":"245","author":"Satyam","year":"2022","journal-title":"Transl Res"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e0225516","DOI":"10.1371\/journal.pone.0225516","article-title":"Chinese SLE treatment and research group (CSTAR) registry: clinical significance of thrombocytopenia in Chinese patients with systemic lupus erythematosus","volume":"14","author":"Jiang","year":"2019","journal-title":"PLoS One"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"2377","DOI":"10.3390\/jcm10112377","article-title":"Assessment of EULAR\/ACR-2019, SLICC-2012 and ACR-1997 classification criteria in SLE with longstanding disease","volume":"10","author":"Magallares","year":"2021","journal-title":"J Clin Med"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.amjmed.2021.07.015","article-title":"First diagnosis of systemic lupus erythematosus in hospitalized patients: clinical phenotypes and pitfalls for the non-specialist","volume":"135","author":"Kapsala","year":"2022","journal-title":"Am J Med"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e000377","DOI":"10.1136\/lupus-2019-000377","article-title":"Cell-bound complement activation products associate with lupus severity in SLE","volume":"7","author":"Arriens","year":"2020","journal-title":"Lupus Sci Med"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1177\/09612033231171343","article-title":"Significance of the weighted complement domain of the EULAR\/ACR classification criteria in juvenile onset systemic lupus erythematosus","volume":"32","author":"Kisaoglu","year":"2023","journal-title":"Lupus"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1695383\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T06:34:31Z","timestamp":1765521271000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1695383\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,12]]},"references-count":26,"alternative-id":["10.3389\/fmed.2025.1695383"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1695383","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,12]]},"article-number":"1695383"}}