admin
Kitching, A. R. et al. ANCA-associated vasculitis. Nat. Rev. Dis. Prim. 6, 71 (2020).
Jennette, J. C. et al. 2012 Revised international Chapel Hill consensus conference nomenclature of vasculitides. Arthritis Rheum. 65, 1–11 (2013).
Comarmond, C. et al. Eosinophilic granulomatosis with polyangiitis (Churg‐Strauss): clinical characteristics and long‐term followup of the 383 patients enrolled in the French Vasculitis Study Group cohort. Arthritis Rheum. 65, 270–281 (2013).
Lyons, P. A. et al. Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status. Nat. Commun. 10, 5120 (2019).
Emmi, G. et al. Evidence-based guideline for the diagnosis and management of eosinophilic granulomatosis with polyangiitis. Nat. Rev. Rheumatol. 19, 378–393 (2023).
Franssen, C. F. M. et al. Antiproteinase 3- and antimyeloperoxidase-associated vasculitis. Kidney Int 57, 2195–2206 (2000).
Franssen, C., Gans, R., Kallenberg, C., Hageluken, C. & Hoorntje, S. Disease spectrum of patients with antineutrophil cytoplasmic autoantibodies of defined specificity: distinct differences between patients with anti‐proteinase 3 and anti‐myeloperoxidase autoantibodies. J. Intern. Med. 244, 209–216 (1998).
Lionaki, S. et al. Classification of antineutrophil cytoplasmic autoantibody vasculitides: the role of antineutrophil cytoplasmic autoantibody specificity for myeloperoxidase or proteinase 3 in disease recognition and prognosis. Arthritis Rheum. 64, 3452–3462 (2012).
Weiner, M. et al. Proteinase-3 and myeloperoxidase serotype in relation to demographic factors and geographic distribution in anti-neutrophil cytoplasmic antibody-associated glomerulonephritis. Nephrol. Dial. Transplant. 34, 301–308 (2018).
Quintana, L. F. et al. ANCA serotype and histopathological classification for the prediction of renal outcome in ANCA-associated glomerulonephritis. Nephrol. Dial. Transplant. 29, 1764–1769 (2014).
Suppiah, R. et al. A model to predict cardiovascular events in patients with newly diagnosed Wegener’s granulomatosis and microscopic polyangiitis. Arthritis Care Res. 63, 588–596 (2011).
Lyons, P. A. et al. Genetically distinct subsets within ANCA-associated vasculitis. N. Engl. J. Med. 367, 214–223 (2012).
Merkel, P. A. et al. Identification of functional and expression polymorphisms associated with risk for antineutrophil cytoplasmic autoantibody-associated vasculitis. Arthritis Rheumatol. 69, 1054–1066 (2017).
Trivioli, G. et al. Genetics of ANCA-associated vasculitis: role in pathogenesis, classification and management. Nat. Rev. Rheumatol. 18, 559–574 (2022).
Cornec, D., Cornec-Le Gall, E., Fervenza, F. C. & Specks, U. ANCA-associated vasculitis — clinical utility of using ANCA specificity to classify patients. Nat. Rev. Rheumatol. 12, 570–579 (2016).
Miloslavsky, E. M. et al. Myeloperoxidase–antineutrophil cytoplasmic antibody (ANCA)-positive and ANCA‐negative patients with granulomatosis with polyangiitis (Wegener’s): distinct patient subsets. Arthritis Rheumatol. 68, 2945–2952 (2016).
Comarmond, C. et al. Pulmonary fibrosis in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis: a series of 49 patients and review of the literature. Medicine 93, 340–349 (2014).
Mahr, A. et al. Revisiting the classification of clinical phenotypes of anti-neutrophil cytoplasmic antibody-associated vasculitis: a cluster analysis. Ann. Rheum. Dis. 72, 1003–1010 (2013).
Gisslander, K. et al. Data-driven subclassification of ANCA-associated vasculitis: model-based clustering of a federated international cohort. Lancet Rheumatol. 6, e762–e770 (2024).
Lindberg, H. et al. In-depth analysis of disease manifestations in antineutrophil cytoplasmic antibody-associated vasculitides identifies distinct clinical phenotypes. ACR Open Rheumatol. 7, e70009 (2025).
Mahr, A., Specks, U. & Jayne, D. Subclassifying ANCA-associated vasculitis: a unifying view of disease spectrum. Rheumatology 58, 1707–1709 (2019).
Nakazawa, D., Masuda, S., Tomaru, U. & Ishizu, A. Pathogenesis and therapeutic interventions for ANCA-associated vasculitis. Nat. Rev. Rheumatol. 15, 91–101 (2019).
Jennette, J. C., Falk, R. J., Hu, P. & Xiao, H. Pathogenesis of antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis. Annu. Rev. Pathol. Mech. Dis. 8, 139–160 (2013).
Mahler, M. et al. PR3-ANCA: a promising biomarker for ulcerative colitis with extensive disease. Clin. Chim. Acta 424, 267–273 (2013).
Roth, A. J. et al. Epitope specificity determines pathogenicity and detectability in ANCA-associated vasculitis. J. Clin. Invest. 123, 1773–1783 (2013).
Kain, R. et al. Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis. Nat. Med. 14, 1088–1096 (2008).
Walton, E. W. Giant-cell granuloma of the respiratory tract (Wegener’s granulomatosis). Br. Med. J. 2, 265–270 (1958).
Sánchez Álamo, B. et al. Long-term outcomes and prognostic factors for survival of patients with ANCA-associated vasculitis. Nephrol. Dial. Transpl. 38, 1655–1665 (2023).
Sanchez-Alamo, B. et al. Long-term outcome of kidney function in patients with ANCA-associated vasculitis. Nephrol. Dial. Transplant. 39, 1483–1493 (2024).
Tomasson, G. et al. Assessment of health‐related quality of life as an outcome measure in granulomatosis with polyangiitis (Wegener’s). Arthritis Care Res. 64, 273–279 (2012).
Hellmich, B. et al. EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis. Ann. Rheum. Dis. 66, 605–617 (2007).
Stone, J. H. et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N. Engl. J. Med. 363, 221–232 (2010).
Jayne, D. R. W., Merkel, P. A., Schall, T. J. & Bekker, P. Avacopan for the treatment of ANCA-associated vasculitis. N. Engl. J. Med. 384, 599–609 (2021).
Mukhtyar, C. et al. Modification and validation of the Birmingham Vasculitis Activity Score (version 3). Ann. Rheum. Dis. 68, 1827–1832 (2009).
Chung, S. A. et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol. 73, 1366–1383 (2021).
Hellmich, B. et al. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann. Rheum. Dis. 83, 30–47 (2024).
Floege, J., Jayne, D. R. W., Sanders, J.-S. F., Tesar, V. & Rovin, B. H. KDIGO 2024 clinical practice guideline for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Kidney Int. 105, S71–S116 (2024).
Casal Moura, M. et al. Management of antineutrophil cytoplasmic antibody-associated vasculitis with glomerulonephritis as proposed by the ACR 2021, EULAR 2022 and KDIGO 2021 guidelines/recommendations. Nephrol. Dial. Transplant. 38, 2637–2651 (2023).
Jones, R. B. et al. Mycophenolate mofetil versus cyclophosphamide for remission induction in ANCA-associated vasculitis: a randomised, non-inferiority trial. Ann. Rheum. Dis. 78, 399–405 (2019).
Tuin, J. et al. Mycophenolate mofetil versus cyclophosphamide for the induction of remission in nonlife-threatening relapses of antineutrophil cytoplasmic antibody-associated vasculitis: randomized, controlled trial. Clin. J. Am. Soc. Nephrol. 14, 1021–1028 (2019).
Faurschou, M. et al. Brief Report: long-term outcome of a randomized clinical trial comparing methotrexate to cyclophosphamide for remission induction in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 64, 3472–3477 (2012).
De Groot, K. et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 52, 2461–2469 (2005).
Pagnoux, C. et al. Predictors of treatment resistance and relapse in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis: comparison of two independent cohorts. Arthritis Rheum. 58, 2908–2918 (2008).
Pendolino, A. L. et al. The role of ANCA in the management of cocaine-induced midline destructive lesions or ENT pseudo-granulomatosis with polyangiitis: a London multicentre case series. Laryngoscope 134, 2609–2616 (2024).
Walsh, M. et al. Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis. N. Engl. J. Med. 382, 622–631 (2020).
Furuta, S. et al. Effect of reduced-dose vs high-dose glucocorticoids added to rituximab on remission induction in ANCA-associated vasculitis: a randomized clinical trial. JAMA 325, 2178 (2021).
Smith, R. M. et al. Rituximab as therapy to induce remission after relapse in ANCA-associated vasculitis. Ann. Rheum. Dis. 79, 1243–1249 (2020).
Jayne, D. R. W. et al. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J. Am. Soc. Nephrol. 18, 2180–2188 (2007).
Chanouzas, D. et al. Intravenous pulse methylprednisolone for induction of remission in severe ANCA associated vasculitis: a multi-center retrospective cohort study. BMC Nephrol. 20, 58 (2019).
Waki, D. et al. Initial high-dose corticosteroids and renal impairment are risk factors for early severe infections in elderly patients with antineutrophil cytoplasmic autoantibody-associated vasculitis: a retrospective observational study. Medicine 99, e19173 (2020).
van Daalen, E. E. et al. Effect of rituximab on malignancy risk in patients with ANCA-associated vasculitis. Ann. Rheum. Dis. 76, 1064–1069 (2017).
Specks, U. et al. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N. Engl. J. Med. 369, 417–427 (2013).
Geetha, D. et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis with renal involvement. J. Am. Soc. Nephrol. 26, 976–985 (2015).
Casal Moura, M. et al. Efficacy of rituximab and plasma exchange in antineutrophil cytoplasmic antibody-associated vasculitis with severe kidney disease. J. Am. Soc. Nephrol. 31, 2688–2704 (2020).
Geetha, D. et al. Rituximab for treatment of severe renal disease in ANCA associated vasculitis. J. Nephrol. 29, 195–201 (2016).
Casal Moura, M. et al. Predictive factors of renal recovery and progression to end-stage kidney disease in patients with antineutrophil cytoplasmic autoantibody-associated vasculitis with severe kidney disease. Kidney Int. Rep. 9, 1284–1297 (2024).
Cortazar, F. B. et al. Combination therapy with rituximab and cyclophosphamide for remission induction in ANCA vasculitis. Kidney Int. Rep. 3, 394–402 (2018).
Gulati, K. et al. Combination treatment with rituximab, low-dose cyclophosphamide and plasma exchange for severe antineutrophil cytoplasmic antibody-associated vasculitis. Kidney Int. 100, 1316–1324 (2021).
Jones, R. B., Luqmani, R., Savage, C. O., van Paassen, P. & Westman, K. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N. Engl. J. Med. 363, 211–220 (2010).
Pepper, R. J. et al. A novel glucocorticoid-free maintenance regimen for anti-neutrophil cytoplasm antibody-associated vasculitis. Rheumatology 58, 260–268 (2018).
Odler, B. et al. The effects of plasma exchange and glucocorticoids on early kidney function among patients with ANCA-associated vasculitis in the PEXIVAS trial. Kidney Int. 107, 558–567 (2025).
Trivioli, G. et al. Slowly progressive anti-neutrophil cytoplasmic antibody-associated renal vasculitis: clinico-pathological characterization and outcome. Clin. Kidney J. 14, 332–340 (2021).
De Joode, A. A. E., Sanders, J. S. F. & Stegeman, C. A. Renal survival in proteinase 3 and myeloperoxidase ANCA-associated systemic vasculitis. Clin. J. Am. Soc. Nephrol. 8, 1709–1717 (2013).
Walsh, M. et al. The effects of plasma exchange in patients with ANCA-associated vasculitis: an updated systematic review and meta-analysis. BMJ 376, e064604 (2022).
Zeng, L. et al. Plasma exchange and glucocorticoid dosing for patients with ANCA-associated vasculitis: a clinical practice guideline. BMJ 376, e064597 (2022).
Tyrberg, L., Andersson, F., Uhlin, F., Hellmark, T. & Segelmark, M. Using imlifidase to elucidate the characteristics and importance of anti-GBM antibodies produced after start of treatment. Nephrol. Dial. Transplant. 39, 45–54 (2023).
He, P. et al. Prevalence and risk factors of relapse in patients with ANCA-associated vasculitis receiving cyclophosphamide induction: a systematic review and meta-analysis of large observational studies. Rheumatology 60, 1067–1079 (2021).
McClure, M. E. et al. Evaluation of PR3-ANCA status after rituximab for ANCA-associated vasculitis. J. Clin. Rheumatol. 25, 217–223 (2019).
Merkel, P. et al. A multicenter, randomized, controlled trial to evaluate the effects of low-dose glucocorticoids compared to stopping glucocorticoids to maintain remission of granulomatosis with polyangiitis: The TAPIR trial. Arthritis Rheumatol. 76 (Suppl. 9), abstr. (2024).
Guillevin, L. et al. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N. Engl. J. Med. 371, 1771–1780 (2014).
Smith, R. M. et al. Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial. Ann. Rheum. Dis. 82, 937–944 (2023).
Charles, P. et al. Long-term rituximab use to maintain remission of antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann. Intern. Med. 173, 179–187 (2020).
Karras, A. et al. Randomised controlled trial of prolonged treatment in the remission phase of ANCA-associated vasculitis. Ann. Rheum. Dis. 76, 1662–1668 (2017).
Tieu, J. et al. Rituximab associated hypogammaglobulinemia in autoimmune disease. Front. Immunol. 12, 671503 (2021).
Charles, P. et al. Comparison of individually tailored versus fixed-schedule rituximab regimen to maintain ANCA-associated vasculitis remission: results of a multicentre, randomised controlled, phase III trial (MAINRITSAN2). Ann. Rheum. Dis. 77, 1143–1149 (2018).
Tomasson, G., Grayson, P. C., Mahr, A. D., LaValley, M. & Merkel, P. A. Value of ANCA measurements during remission to predict a relapse of ANCA-associated vasculitis — a meta-analysis. Rheumatology 51, 100–109 (2012).
Casal Moura, M. et al. Maintenance of remission and risk of relapse in myeloperoxidase-positive ANCA-associated vasculitis with kidney involvement. Clin. J. Am. Soc. Nephrol. 18, 47–59 (2023).
Kemna, M. J. et al. ANCA as a predictor of relapse: useful in patients with renal involvement but not in patients with nonrenal disease. J. Am. Soc. Nephrol. 26, 537–542 (2015).
Alberici, F. et al. Long-term follow-up of patients who received repeat-dose rituximab as maintenance therapy for ANCA-associated vasculitis. Rheumatology 54, 1153–1160 (2015).
Mescia, F. et al. Sustained post-rituximab B-cell depletion is common in ANCA-associated vasculitis and is affected by sex and renal function. Nephrol. Dial. Transplant. 39, 683–693 (2024).
Zonozi, R. et al. Maintenance of remission of ANCA vasculitis by rituximab based on B cell repopulation versus serological flare: a randomised trial. Ann. Rheum. Dis. 83, 351–359 (2024).
Uchida, L. et al. Long-term surveillance study of rituximab originator treated patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Rheumatol. Adv. Pract. 8, rkae090 (2024).
Voswinkel, J. et al. B lymphocyte maturation in Wegener’s granulomatosis: a comparative analysis of VH genes from endonasal lesions. Ann. Rheum. Dis. 65, 859–864 (2006).
Popa, E. R., Stegeman, C. A., Bos, N. A., Kallenberg, C. G. M. & Tervaert, J. W. C. Differential B- and T-cell activation in Wegener’s granulomatosis. J. Allergy Clin. Immunol. 103, 885–894 (1999).
Moller, B. et al. Class-switched B cells display response to therapeutic B cell depletion in rheumatoid arthritis. Arthritis Res. Ther. 11, R62 (2009).
Nakou, M. et al. Rituximab therapy reduces activated B cells in both the peripheral blood and bone marrow of patients with rheumatoid arthritis: depletion of memory B cells correlates with clinical response. Arthritis Res. Ther. 11, R131 (2009).
Ramwadhdoebe, T. H. et al. Effect of rituximab treatment on T and B cell subsets in lymph node biopsies of patients with rheumatoid arthritis. Rheumatology 58, 1075–1085 (2019).
Kavanaugh, A. et al. Assessment of rituximab’s immunomodulatory synovial effects (ARISE trial). 1: clinical and synovial biomarker results. Ann. Rheum. Dis. 67, 402–408 (2008).
Thiel, J. et al. Defects in B-lymphopoiesis and B-cell maturation underlie prolonged B-cell depletion in ANCA-associated vasculitis. Ann. Rheum. Dis. 83, 1536–1548 (2024).
Wilde, B. et al. T cells in ANCA-associated vasculitis: what can we learn from lesional versus circulating T cells? Arthritis Res. Ther. 12, 204 (2010).
Schmitt, W. H., Heesen, C., Csernok, E., Rautmann, A. & Gross, W. L. Elevated serum levels of soluble interleukin-2 receptor in patients with Wegener’s granulomatosis. association with disease activity. Arthritis Rheum. 35, 1088–1096 (1992).
McKinney, E. F. et al. A CD8+ T cell transcription signature predicts prognosis in autoimmune disease. Nat. Med. 16, 586–591 (2010).
Nogueira, E. et al. Serum IL-17 and IL-23 levels and autoantigen-specific Th17 cells are elevated in patients with ANCA-associated vasculitis. Nephrol. Dial. Transplant. 25, 2209–2217 (2010).
Gan, P.-Y. et al. Biologicals targeting T helper cell subset differentiating cytokines are effective in the treatment of murine anti-myeloperoxidase glomerulonephritis. Kidney Int. 96, 1121–1133 (2019).
Lee, D. S. W., Rojas, O. L. & Gommerman, J. L. B cell depletion therapies in autoimmune disease: advances and mechanistic insights. Nat. Rev. Drug. Discov. 20, 179–199 (2021).
Hartinger, J. M., Kratky, V., Hruskova, Z., Slanar, O. & Tesar, V. Implications of rituximab pharmacokinetic and pharmacodynamic alterations in various immune-mediated glomerulopathies and potential anti-CD20 therapy alternatives. Front. Immunol. 13, 1024068 (2022).
McAdoo, S. P. et al. Ofatumumab for B cell depletion therapy in ANCA-associated vasculitis: a single-centre case series. Rheumatology 55, 1437–1442 (2016).
Amudala, N. A. et al. Obinutuzumab as treatment for ANCA-associated vasculitis. Rheumatology 61, 3814–3817 (2022).
McGovern, D. P. et al. Study protocol for a randomised, phase II, double-blind, experimental medicine study of obinutuzumab versus rituximab in ANCA-associated vasculitis: ObiVas. BMJ Open. 14, e083277 (2024).
Furie, R. A. et al. Efficacy and safety of obinutuzumab in active lupus nephritis. N. Engl. J. Med. 392, 1471–1483 (2025).
Hu, X. et al. Comparison of obinutuzumab and rituximab for treating primary membranous nephropathy. Clin. J. Am. Soc. Nephrol. CJASN 19, 1594–1602 (2024).
Cree, B. A. C. et al. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet Lond. Engl. 394, 1352–1363 (2019).
Flanagan, E. P. et al. Inebilizumab for treatment of neuromyelitis optica spectrum disorder in patients with prior rituximab use from the N-MOmentum study. Mult. Scler. Relat. Disord. 57, 103352 (2022).
Holzer, M.-T. et al. Daratumumab for autoimmune diseases: a systematic review. RMD Open. 9, e003604 (2023).
Ostendorf, L. et al. Daratumumab for the treatment of refractory ANCA-associated vasculitis. RMD Open. 9, e002742 (2023).
Rixecker, T. M. et al. Daratumumab for a patient with refractory antineutrophil cytoplasmatic antibody-associated vasculitis. JAMA Intern. Med. 183, 615–618 (2023).
Angeletti, A. et al. Combined rituximab and daratumumab treatment in difficult-to-treat nephrotic syndrome cases. Kidney Int. Rep. 9, 1892–1896 (2024).
Chiarenza, D. S. et al. Case report: single infusion of combined anti-CD20 and anti-CD38 monoclonal antibodies in pediatric refractory lupus nephritis. Front. Immunol. 16, 1525892 (2025).
Stohl, W. & Hilbert, D. M. The discovery and development of belimumab: the anti-BLyS-lupus connection. Nat. Biotechnol. 30, 69–77 (2012).
Mackay, F. & Schneider, P. Cracking the BAFF code. Nat. Rev. Immunol. 9, 491–502 (2009).
Ota, M. et al. Regulation of the B cell receptor repertoire and self-reactivity by BAFF. J. Immunol. 185, 4128–4136 (2010).
Cheema, G. S., Roschke, V., Hilbert, D. M. & Stohl, W. Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases. Arthritis Rheum. 44, 1313–1319 (2001).
Bader, L., Koldingsnes, W. & Nossent, J. B-lymphocyte activating factor levels are increased in patients with Wegener’s granulomatosis and inversely correlated with ANCA titer. Clin. Rheumatol. 29, 1031–1035 (2010).
Holden, N. J. et al. ANCA-stimulated neutrophils release BLyS and promote B cell survival: a clinically relevant cellular process. Ann. Rheum. Dis. 70, 2229–2233 (2011).
Jayne, D. et al. Efficacy and safety of belimumab and azathioprine for maintenance of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled study. Arthritis Rheumatol. 71, 952–963 (2019).
McClure, M. E. et al. A randomised study of rituximab and belimumab sequential therapy in PR3 ANCA-associated vasculitis (COMBIVAS): design of the study protocol. Trials 24, 180 (2023).
Carter, L. M., Isenberg, D. A. & Ehrenstein, M. R. Elevated serum BAFF levels are associated with rising anti-double-stranded DNA antibody levels and disease flare following B cell depletion therapy in systemic lupus erythematosus. Arthritis Rheum. 65, 2672–2679 (2013).
Shipa, M. et al. Effectiveness of belimumab after rituximab in systemic lupus erythematosus: a randomized controlled trial. Ann. Intern. Med. 174, 1647–1657 (2021).
Aranow, C. et al. Efficacy and safety of sequential therapy with subcutaneous belimumab and one cycle of rituximab in patients with systemic lupus erythematosus: the phase 3, randomised, placebo-controlled BLISS-BELIEVE study. Ann. Rheum. Dis. 83, 1502–1512 (2024).
Shimojima, Y. et al. Features of BAFF and APRIL receptors on circulating B cells in antineutrophil cytoplasmic antibody-associated vasculitis. Clin. Exp. Immunol. 213, 125–137 (2023).
Schett, G. et al. Advancements and challenges in CAR T cell therapy in autoimmune diseases. Nat. Rev. Rheumatol. 20, 531–544 (2024).
Mackensen, A. et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat. Med. 28, 2124–2132 (2022).
Müller, F. et al. CD19 CAR T-cell therapy in autoimmune disease — A case series with follow-up. N. Engl. J. Med. 390, 687–700 (2024).
Lodka, D. et al. CD19-targeting CAR T cells protect from ANCA-induced acute kidney injury. Ann. Rheum. Dis. 83, 499–507 (2024).
Minopoulou, I. et al. Anti-CD19 CAR T cell therapy induces antibody seroconversion and complete B cell depletion in the bone marrow of a therapy-refractory patient with ANCA-associated vasculitis. Ann. Rheum. Dis. 84, e4–e7 (2025).
Depil, S., Duchateau, P., Grupp, S. A., Mufti, G. & Poirot, L. Off-the-shelf’ allogeneic CAR T cells: development and challenges. Nat. Rev. Drug. Discov. 19, 185–199 (2020).
Lee, J. et al. Antigen-specific B cell depletion for precision therapy of mucosal pemphigus vulgaris. J. Clin. Invest. 130, 6317–6324 (2020).
Oh, S. et al. Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells. Nat. Biotechnol. 41, 1229–1238 (2023).
Bucci, L. et al. Bispecific T cell engager therapy for refractory rheumatoid arthritis. Nat. Med. 30, 1593–1601 (2024).
Szpirt, W. M., Heaf, J. G. & Petersen, J. Plasma exchange for induction and cyclosporine A for maintenance of remission in Wegener’s granulomatosis — a clinical randomized controlled trial. Nephrol. Dial. Transplant. 26, 206–213 (2011).
Berden, A. E. et al. Tubular lesions predict renal outcome in antineutrophil cytoplasmic antibody-associated glomerulonephritis after rituximab therapy. J. Am. Soc. Nephrol. 23, 313–321 (2012).
Gopaluni, S. et al. Alemtuzumab for refractory primary systemic vasculitis — a randomised controlled dose ranging clinical trial of efficacy and safety (ALEVIATE). Arthritis Res. Ther. 24, 81 (2022).
Langford, C. A. et al. An open-label trial of abatacept (CTLA4-IG) in non-severe relapsing granulomatosis with polyangiitis (Wegener’s). Ann. Rheum. Dis. 73, 1376–1379 (2014).
Langford, C. et al. A randomized, double-blind, placebo-controlled trial of Abatacept for the treatment of relapsing, non-severe, granulomatosis with polyangiitis. Arthritis Rheumatol. 76 (Suppl. 9), abstr. (2024).
Engesser, J. et al. Immune profiling-based targeting of pathogenic T cells with ustekinumab in ANCA-associated glomerulonephritis. Nat. Commun. 15, 8220 (2024).
Jayne, D. Complement inhibition in ANCA vasculitis. Nephrol. Ther. 15, 409–412 (2019).
Gou, S.-J., Yuan, J., Wang, C., Zhao, M.-H. & Chen, M. Alternative complement pathway activation products in urine and kidneys of patients with ANCA-associated GN. Clin. J. Am. Soc. Nephrol. 8, 1884–1891 (2013).
Hilhorst, M. et al. Complement in ANCA-associated glomerulonephritis. Nephrol. Dial. Transplant. 32, 1302–1313 (2017).
Gou, S.-J., Yuan, J., Chen, M., Yu, F. & Zhao, M.-H. Circulating complement activation in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Kidney Int. 83, 129–137 (2013).
Xiao, H., Schreiber, A., Heeringa, P., Falk, R. J. & Jennette, J. C. Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies. Am. J. Pathol. 170, 52–64 (2007).
Huugen, D. et al. Inhibition of complement factor C5 protects against anti-myeloperoxidase antibody-mediated glomerulonephritis in mice. Kidney Int. 71, 646–654 (2007).
Schreiber, A. et al. C5a receptor mediates neutrophil activation and ANCA-induced glomerulonephritis. J. Am. Soc. Nephrol. 20, 289–298 (2009).
Xiao, H. et al. C5a receptor (CD88) blockade protects against MPO-ANCA GN. J. Am. Soc. Nephrol. 25, 225–231 (2014).
Jayne, D. R. W. et al. Randomized trial of C5a receptor inhibitor avacopan in ANCA-associated vasculitis. J. Am. Soc. Nephrol. 28, 2756–2767 (2017).
Merkel, P. A. et al. Adjunctive treatment with avacopan, an oral C5a receptor inhibitor, in patients with antineutrophil cytoplasmic antibody-associated vasculitis. ACR Open. Rheumatol. 2, 662–671 (2020).
Strand, V. et al. The impact of treatment with avacopan on health-related quality of life in antineutrophil cytoplasmic antibody-associated vasculitis: a post-hoc analysis of data from the ADVOCATE trial. Lancet Rheumatol. 5, e451–e460 (2023).
Cortazar, F. B. et al. Renal recovery for patients with ANCA-associated vasculitis and low EGFR in the ADVOCATE trial of avacopan. Kidney Int. Rep. 8, 860–870 (2023).
Jayne, D. R. W. et al. AB1241 design of Avacostar: a real-world study of avacopan in ANCA-associated vasculitis (AAV). in Scientific Abstracts 1960.2-1960, (BMJ Publishing Group and European League Against Rheumatism, 2024).
Chalkia, A. et al. Avacopan for ANCA-associated vasculitis with hypoxic pulmonary haemorrhage. Nephrol. Dial. Transplant. 39, 1473–1482 (2024).
Zonozi, R. et al. Real-world experience with avacopan in antineutrophil cytoplasmic autoantibody-associated vasculitis. Kidney Int. Rep. 9, 1783–1791 (2024).
Zimmermann, J. et al. Avacopan in anti-neutrophil cytoplasmic autoantibodies-associated vasculitis in a real-world setting. Kidney Int. Rep. 9, 2803–2808 (2024).
Bamberg, C. E. et al. The C5a receptor (C5aR) C5L2 Is a modulator of C5aR-mediated signal transduction. J. Biol. Chem. 285, 7633–7644 (2010).
Merkel, P. et al. A randomized, double-blind, phase II study of glucocorticoid replacement by vilobelimab, an anti-C5a monoclonal antibody, in ANCA-associated vasculitis. Arthritis Rheumatol. 74 (Suppl. 9), abstr. (2022).
Kitamura, F. et al. Anti-neutrophil cytoplasmic antibody-associated vasculitis complicated by thrombotic microangiopathy with posterior reversible encephalopathy syndrome successfully treated with eculizumab: a case report. Mod. Rheumatol. Case Rep. 6, 254–259 (2022).
Manenti, L., Urban, M. L., Maritati, F., Galetti, M. & Vaglio, A. Complement blockade in ANCA-associated vasculitis: an index case, current concepts and future perspectives. Intern. Emerg. Med. 12, 727–731 (2017).
Ribes, D., Belliere, J., Piedrafita, A. & Faguer, S. Glucocorticoid-free induction regimen in severe ANCA-associated vasculitis using a combination of rituximab and eculizumab. Rheumatology 58, 2335–2337 (2019).
Lucientes-Continente, L. et al. Complement alternative pathway determines disease susceptibility and severity in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Kidney Int. 105, 177–188 (2024).
Manenti, L. et al. Association of serum C3 concentration and histologic signs of thrombotic microangiopathy with outcomes among patients with ANCA-associated renal vasculitis. Clin. J. Am. Soc. Nephrol. 10, 2143–2151 (2015).
Moiseev, S. et al. The alternative complement pathway in ANCA-associated vasculitis: further evidence and a meta-analysis. Clin. Exp. Immunol. 202, 394–402 (2020).
Uhlin, F. et al. Endopeptidase cleavage of anti-glomerular basement membrane antibodies in vivo in severe kidney disease: an open-label phase 2a study. J. Am. Soc. Nephrol. 33, 829–838 (2022).
Enghard, P. et al. Imlifidase as novel treatment strategy in anti-neutrophil cytoplasmic antibody-induced pulmonary-renal syndrome. Kidney Int. 100, 1344–1345 (2021).
Seren, S. et al. Consequences of cathepsin C inactivation for membrane exposure of proteinase 3, the target antigen in autoimmune vasculitis. J. Biol. Chem. 293, 12415–12428 (2018).
Jerke, U. et al. Targeting cathepsin C in PR3-ANCA vasculitis. J. Am. Soc. Nephrol. 33, 936–947 (2022).
Chalmers, J. D. et al. Phase 2 trial of the DPP-1 inhibitor brensocatib in bronchiectasis. N. Engl. J. Med. 383, 2127–2137 (2020).
O’Sullivan, K. M. et al. Renal participation of myeloperoxidase in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. Kidney Int. 88, 1030–1046 (2015).
Antonelou, M. et al. Therapeutic myeloperoxidase inhibition attenuates neutrophil activation, ANCA-mediated endothelial damage, and crescentic GN. J. Am. Soc. Nephrol. 31, 350–364 (2020).
Lam, C. S. P. et al. Myeloperoxidase inhibition in heart failure with preserved or mildly reduced ejection fraction: SATELLITE trial results. J. Card. Fail. 30, 104–110 (2024).
Prendecki, M. et al. Syk activation in circulating and tissue innate immune cells in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol. 75, 84–97 (2023).
McAdoo, S. P. et al. Correlation of disease activity in proliferative glomerulonephritis with glomerular spleen tyrosine kinase expression. Kidney Int. 88, 52–60 (2015).
McAdoo, S. P. et al. Spleen tyrosine kinase inhibition is an effective treatment for established vasculitis in a pre-clinical model. Kidney Int. 97, 1196–1207 (2020).
Kessenbrock, K. et al. Netting neutrophils in autoimmune small-vessel vasculitis. Nat. Med. 15, 623–625 (2009).
Kusunoki, Y. et al. Peptidylarginine deiminase inhibitor suppresses neutrophil extracellular trap formation and MPO-ANCA production. Front. Immunol. 7, 227 (2016).
Shiratori-Aso, S. & Nakazawa, D. The involvement of NETs in ANCA-associated vasculitis. Front. Immunol. 14, 1261151 (2023).
O’Sullivan, K. M., Gan, P. Y., Kitching, A. R. & Holdsworth, S. SAT-012 Peptidyl arginase deiminase 4 inhibition attenuates inflammation in murine experimental myeloperoxidase cytoplasmic antibody associated glomerulonephritis. Kidney Int. Rep. 4, S6 (2019).
Roehlen, N. et al. A monoclonal antibody targeting nonjunctional claudin-1 inhibits fibrosis in patient-derived models by modulating cell plasticity. Sci. Transl. Med. 14, eabj4221 (2022).
Cerullo, D. et al. Characterization of a rat model of myeloperoxidase-anti-neutrophil cytoplasmic antibody-associated crescentic glomerulonephritis. Nephron 145, 428–444 (2021).
Teixeira, G. et al. Claudin-1 is a therapeutic target for crescentic glomerulonephritis: TH-PO531. J. Am. Soc. Nephrol. 34, 238–238 (2023).
Maillet, T. et al. Usual interstitial pneumonia in ANCA-associated vasculitis: a poor prognostic factor. J. Autoimmun. 106, 102338 (2020).
Shoda, T. et al. SAT0548 Prognostic factors for interstitial lung disease with microscopic polyangiitis. Ann. Rheum. Dis. 77, 1128 (2018).
Watanabe, T. et al. Prognosis of pulmonary fibrosis presenting with a usual interstitial pneumonia pattern on computed tomography in patients with myeloperoxidase anti-neutrophil cytoplasmic antibody-related nephritis: a retrospective single-center study. BMC Pulm. Med. 19, 194 (2019).
Song, M. J. et al. Effectiveness of pirfenidone in idiopathic pulmonary fibrosis according to the autoantibody status: a retrospective cohort study. BMC Pulm. Med. 21, 145 (2021).
O’Reilly, V. P. et al. Urinary soluble CD163 in active renal vasculitis. J. Am. Soc. Nephrol. 27, 2906–2916 (2016).
Moran, S. M. et al. Urinary soluble CD163 and monocyte chemoattractant protein-1 in the identification of subtle renal flare in anti-neutrophil cytoplasmic antibody-associated vasculitis. Nephrol. Dial. Transplant. 35, 283–291 (2020).
Moran, S. M. et al. The clinical application of urine soluble CD163 in ANCA-associated vasculitis. J. Am. Soc. Nephrol. 32, 2920–2932 (2021).
Endo, N. et al. Urinary soluble CD163 level reflects glomerular inflammation in human lupus nephritis. Nephrol. Dial. Transplant. 31, 2023–2033 (2016).
Gamerith, G. et al. Association of baseline soluble immune checkpoints with the risk of relapse in PR3-ANCA vasculitis following induction of remission. Ann. Rheum. Dis. 82, 253–261 (2023).
Barnes, E. et al. SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease. Nat. Med. 29, 1760–1774 (2023).
Pearce, F. A. et al. Antibody prevalence after three or more COVID-19 vaccine doses in individuals who are immunosuppressed in the UK: a cross-sectional study from MELODY. Lancet Rheumatol. 5, e461–e473 (2023).
Ammitzbøll, C. et al. Rituximab-treated rheumatic patients: B cells predict seroconversion after COVID-19 boost or revaccination in initial vaccine non-responders. Rheumatology 62, 2544–2549 (2023).
Marty, P. K. et al. Antigen specific humoral and cellular immunity following SARS-CoV-2 vaccination in ANCA-associated vasculitis patients receiving B-cell depleting therapy. Front. Immunol. 13, 834981 (2022).
Zonozi, R. et al. T cell responses to SARS-CoV-2 infection and vaccination are elevated in B cell deficiency and reduce risk of severe COVID-19. Sci. Transl. Med. 15, eadh4529 (2023).
Terrier, B. et al. Innovative anti-pneumococcal vaccine strategies versus standard vaccination regimen in patients with ANCA-associated vasculitides receiving rituximab therapy: a multicenter randomized controlled trial (PNEUMOVAS). Abstract Number: L16 Innovative Anti-pneumococcal Vaccine Strategies versus Standard Vaccination Regimen in Patients with ANCA-associated Vasculitides Receiving Rituximab Therapy: A Multicenter Randomized Controlled Trial (PNEUMOVAS) (2022).
Flossmann, O. et al. Long-term patient survival in ANCA-associated vasculitis. Ann. Rheum. Dis. 70, 488–494 (2011).
Moiseev, S. et al. Traditional and disease-specific risk factors for cardiovascular events in antineutrophil cytoplasmic antibody-associated vasculitis: a multinational retrospective study. J. Rheumatol. 50, 1145–1151 (2023).
Morgan, M. D. et al. Increased incidence of cardiovascular events in patients with antineutrophil cytoplasmic antibody-associated vasculitides: a matched-pair cohort study. Arthritis Rheum. 60, 3493–3500 (2009).
Heerspink, H. J. L. et al. Dapagliflozin in patients with chronic kidney disease. N. Engl. J. Med. 383, 1436–1446 (2020).
The EMPA-KIDNEY Collaborative Group. Empagliflozin in patients with chronic kidney disease. N. Engl. J. Med. 388, 117–127 (2023).
Heerspink, H. J. L. et al. Design and baseline characteristics of the finerenone, in addition to standard of care, on the progression of kidney disease in patients with non-diabetic chronic kidney disease (FIND-CKD) randomized trial. Nephrol. Dial. Transplant. 40, 308–319 (2025).
Farrah, T. E. et al. Arterial stiffness, endothelial dysfunction and impaired fibrinolysis are pathogenic mechanisms contributing to cardiovascular risk in ANCA-associated vasculitis. Kidney Int. 102, 1115–1126 (2022).
Harper, L. et al. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up. Ann. Rheum. Dis. 71, 955–960 (2012).
de Groot, K. et al. Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann. Intern. Med. 150, 670–680 (2009).
Jayne, D. R. et al. Intravenous immunoglobulin for ANCA-associated systemic vasculitis with persistent disease activity. QJM 93, 433–439 (2000).
Furuta, S. et al. Reduced-dose versus high-dose glucocorticoids added to rituximab on remission induction in ANCA-associated vasculitis: predefined 2-year follow-up study. Ann. Rheum. Dis. 83, 96–102 (2024).
Jayne, D. et al. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N. Engl. J. Med. 349, 36–44 (2003).
Hiemstra, T. F. et al. Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled trial. JAMA 304, 2381 (2010).
Pagnoux, C. et al. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N. Engl. J. Med. 359, 2790–2803 (2008).
Wegener’s Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener’s granulomatosis. N. Engl. J. Med. 352, 351–361 (2005).
Metzler, C. et al. Elevated relapse rate under oral methotrexate versus leflunomide for maintenance of remission in Wegener’s granulomatosis. Rheumatology 46, 1087–1091 (2007).
Henderson, S. R. et al. Proteinase 3 promotes formation of multinucleated giant cells and granuloma-like structures in patients with granulomatosis with polyangiitis. Ann. Rheum. Dis. 82, 848–856 (2023).
Lim, B. et al. The effect of intranasal niclosamide on nasal symptoms in patients with ENT manifestations of ANCA-associated vasculitis (AAV): post hoc analysis of subset of patients recruited to the PROTECT-V trial. Arthritis Rheumatol. 76 (Suppl. 9), abstr. (2024).
Learoyd, A. E. et al. The HAVEN study-hydroxychloroquine in ANCA vasculitis evaluation — a multicentre, randomised, double-blind, placebo-controlled trial: study protocol and statistical analysis plan. Trials 24, 261 (2023).
