{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:54:07Z","timestamp":1791262447391,"version":"4.1.0"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"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>ANCA-associated vasculitis (AAV) is characterized by pauci-immune small-vessel inflammation driven predominantly by neutrophil activation, in contrast to immune-complex\u2013mediated glomerulopathies in which complement consumption tracks disease activity and renal injury severity. Serum C3 at diagnosis has repeatedly been associated with renal and patient survival in AAV, yet it remains unresolved whether complement fractions reflect the extent of renal injury in a dose-dependent manner, as they do in lupus nephritis, and how complement relates to immunoglobulin class profiles across ANCA serotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective single-center cohort study included 73 patients with AAV (PR3-ANCA, n = 39; MPO-ANCA, n = 34) who had complete complement and immunoglobulin data at admission and at least 6 months of follow-up at a tertiary nephrology center. Serum C3, C4, IgG, IgA, and IgM were measured at baseline before the initiation of immunosuppressive treatment; no sample was obtained after plasma exchange had begun. Patients were stratified by ANCA serotype and chronic kidney disease (CKD) severity. Associations with disease activity, inflammatory indices, and 6-month outcomes were explored using non-parametric comparisons, Spearman correlations, false discovery rate (FDR) correction, and sensitivity analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>C3 and C4 lay within the reference interval in 97.3% and 86.3% of patients, respectively, and showed no gradient across CKD severity groups (C3 p = 0.453; C4 p\u00a0= 0.550), whereas the inflammatory indices C-NLR and PLR differed across those groups. IgA was nominally higher in patients with MPO-ANCA than in those with PR3-ANCA (2.60 [1.92\u20132.88] vs. 2.11 [1.78\u20132.30] g\/L, p = 0.011) but did not retain significance after FDR adjustment across the five immune parameters (q = 0.055), and all values lay within the reference interval. IgG correlated with ESR (\u03c1 = +0.40, p &amp;lt; 0.001) and \u0394eGFR at 6 months (\u03c1 = +0.26, p = 0.037). Serum C4 was higher in the eight patients who did not achieve clinical remission (0.35 [0.28\u20130.44] vs. 0.28 [0.20\u20130.33] g\/L, nominal p = 0.037; FDR q = 0.184; AUC 0.729, 95% bootstrap CI 0.473\u20130.953, an interval that includes 0.5). C3 correlated inversely with neutrophil-to-lymphocyte ratio (NLR) (\u03c1 = \u22120.24, p = 0.043).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Frank complement consumption was uncommon in this cohort, and neither C3 nor C4 graded renal injury severity, consistent with pauci-immune pathogenesis and in contrast to lupus nephritis. These data do not conflict with published cohorts in which relatively lower C3 predicted adverse renal outcomes; rather, they suggest that the prognostic signal resides in variation within the reference interval rather than in measurable consumption proportional to glomerular injury. The serotype difference in IgA and the association between C4 and failure to achieve remission are exploratory observations that did not withstand correction for multiple comparisons. Because induction-regimen coding was sparse and heterogeneous, no treatment-adjusted IgA model was retained. The C4 association was based on only eight non-remission events and, notably, ran in the opposite direction to a complement-consumption interpretation; it requires confirmation in larger, prospective cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1912981","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:26:33Z","timestamp":1791260793000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Complement and immunoglobulin profiles in ANCA-associated vasculitis with renal involvement: a serotype-stratified analysis of disease activity and renal outcomes"],"prefix":"10.3389","volume":"17","author":[{"given":"Sonja","family":"Golubovi\u0107","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Novi Sad","place":["Novi Sad, Serbia"]},{"name":"Clinic for Nephrology and Clinical Immunology, University Clinical Center of 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