Complement in ANCA vasculitis, insights on pathophysiology and targeted therapies
Main Article Content
Abstract
Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a debilitating disease with the potential to cause significant morbidity and mortality if not treated. The pathogenesis of this disease is not understood, though emerging evidence suggests that alternative complement pathway system is involved. C5a, mediates several pro-inflammatory effects through its receptor C5aR. Avacopan, targets C5a by preventing it from binding to its receptor C5aR. Complement dysregulation, imbalance between regulatory activity of Factor H and stimulation by Factor H related proteins, has been identified as a new mechanism of disease.
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How to Cite
SRINIVISA, Vinay.
Complement in ANCA vasculitis, insights on pathophysiology and targeted therapies.
Medical Research Archives, [S.l.], v. 12, n. 8, aug. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5594>. Date accessed: 06 sep. 2024.
doi: https://doi.org/10.18103/mra.v12i8.5594.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Augusto, J.-F., Langs, V., Demiselle, J., Lavigne, C., Brilland, B., Duveau, A., Poli, C., Chevailler, A., Croue, A., Tollis, F., Sayegh, J., & Subra, J.-F. (2016). Low serum complement C3 levels at diagnosis of renal anca-associated vasculitis is associated with poor prognosis. PLOS ONE, 11(7), e0158871. https://doi.org/10.1371/journal.pone.0158871
2. Boon, C. J. F., van de Kar, N. C., Klevering, B. J., Keunen, J. E. E., Cremers, F. P. M., Klaver, C. C. W., Hoyng, C. B., Daha, M. R., & den Hollander, A. I. (2009). The spectrum of phenotypes caused by variants in the CFH gene. Molecular Immunology, 46(8–9), 1573–1594. https://doi.org/10.1016/j.molimm.2009.02.013
3. Chen, M., Jayne, D. R. W., & Zhao, M.-H. (2017). Complement in ANCA-associated vasculitis: Mechanisms and implications for management. Nature Reviews Nephrology, 13(6), 359–367. https://doi.org/10.1038/nrneph.2017.37
4. Crnogorac, M., Horvatic, I., Kacinari, P., Ljubanovic, D. G., & Galesic, K. (2017). Serum C3 complement levels in ANCA associated vasculitis at diagnosis is a predictor of patient and renal outcome. Journal of Nephrology, 31(2), 257–262. https://doi.org/10.1007/s40620-017-0445-3
5. Csincsi, Á. I., Kopp, A., Zöldi, M., Bánlaki, Z., Uzonyi, B., Hebecker, M., Caesar, J. J. E., Pickering, M. C., Daigo, K., Hamakubo, T., Lea, S. M., Goicoechea de Jorge, E., & Józsi, M. (2015). Factor h–related protein 5 interacts with pentraxin 3 and the extracellular matrix and modulates complement activation. The Journal of Immunology, 194(10), 4963–4973. https://doi.org/10.4049/jimmunol.1403121
6. Csincsi, Á. I., Szabó, Z., Bánlaki, Z., Uzonyi, B., Cserhalmi, M., Kárpáti, É., Tortajada, A., Caesar, J. J. E., Prohászka, Z., Jokiranta, T. S., Lea, S. M., Rodríguez de Córdoba, S., & Józsi, M. (2017). FHR-1 binds to c-reactive protein and enhances rather than inhibits complement activation. The Journal of Immunology, 199(1), 292–303. https://doi.org/10.4049/jimmunol.1600483
7. de Boer, E. C., Thielen, A. J., Langereis, J. D., Kamp, A., Brouwer, M. C., Oskam, N., Jongsma, M. L., Baral, A. J., Spaapen, R. M., Zeerleder, S., Vidarsson, G., Rispens, T., Wouters, D., Pouw, R. B., & Jongerius, I. (2023). The contribution of the alternative pathway in complement activation on cell surfaces depends on the strength of classical pathway initiation. Clinical & Translational Immunology, 12(1). https://doi.org/10.1002/cti2.1436
8. Deshayes, S., Aouba, A., Khoy, K., Mariotte, D., Lobbedez, T., & Martin Silva, N. (2018). Hypocomplementemia is associated with worse renal survival in ANCA-positive granulomatosis with polyangiitis and microscopic polyangiitis. PLOS ONE, 13(4), e0195680. https://doi.org/10.1371/journal.pone.0195680
9. Goicoechea de Jorge, E., Caesar, J. J. E., Malik, T. H., Patel, M., Colledge, M., Johnson, S., Hakobyan, S., Morgan, B. P., Harris, C. L., Pickering, M. C., & Lea, S. M. (2013). Dimerization of complement factor H-related proteins modulates complement activation in vivo. Proceedings of the National Academy of Sciences, 110(12), 4685–4690. https://doi.org/10.1073/pnas.1219260110
10. Haas, M., & Eustace, J. A. (2004). Immune complex deposits in ANCA-associated crescentic glomerulonephritis: A study of 126 cases. Kidney International, 65(6), 2145–2152. https://doi.org/10.1111/j.1523-1755.2004.00632.x
11. Harboe, M., Ulvund, G., Vien, L., Fung, M., & Mollnes, T. E. (2004). The quantitative role of alternative pathway amplification in classical pathway induced terminal complement activation. Clinical and Experimental Immunology, 138(3), 439–446. https://doi.org/10.1111/j.1365-2249.2004.02627.x
12. Hebecker, M., & Józsi, M. (2012). Factor h-related protein 4 activates complement by serving as a platform for the assembly of alternative pathway C3 convertase via its interaction with c3b protein. Journal of Biological Chemistry, 287(23), 19528–19536. https://doi.org/10.1074/jbc.m112.364471
13. Hilhorst, M., van Paassen, P., van Rie, H., Bijnens, N., Heerings-Rewinkel, P., van Breda Vriesman, P., & Cohen Tervaert, J. W. (2015). Complement in ANCA-associated glomerulonephritis. Nephrology Dialysis Transplantation, 32(8), 1302–1313. https://doi.org/10.1093/ndt/gfv288
14. Hook, W. A., Snyderman, R., & Mergenhagen, S. E. (1970). Histamine-Releasing factor generated by the interaction of endotoxin with hamster serum. Infection and Immunity, 2(4), 462–467. https://doi.org/10.1128/iai.2.4.462-467.1970
15. Huugen, D., van Esch, A., Xiao, H., Peutz-Kootstra, C.-J., Buurman, W.-A., Tervaert, J. W. C., Jennette, J.-C., & Heeringa, P. (2007). Inhibition of complement factor C5 protects against anti-myeloperoxidase antibody-mediated glomerulonephritis in mice. Kidney International, 71(7), 646–654. https://doi.org/10.1038/sj.ki.5002103
16. Immunopathological studies of polyarteritis nodosa and wegener’s granulomatosis: A report of 43 patients with 51 renal biopsies. (1983). QJM: An International Journal of Medicine. https://doi.org/10.1093/oxfordjournals.qjmed.a067755
17. Irmscher, S., Brix, S. R., Zipfel, S. L. H., Halder, L. D., Mutlutürk, S., Wulf, S., Girdauskas, E., Reichenspurner, H., Stahl, R. A. K., Jungnickel, B., Wiech, T., Zipfel, P. F., & Skerka, C. (2019). Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-10766-0
18. Jayne, D. (2019). Complement inhibition in ANCA vasculitis. Néphrologie & Thérapeutique, 15(6), 409–412. https://doi.org/10.1016/j.nephro.2019.04.001
19. Jayne, D. (2021, March 28). 26 Lessons learned from complement inhibition in ANCA vasculitis. Abstracts. http://dx.doi.org/10.1136/lupus-2021-la.26
20. Jayne, D. R. W., Bruchfeld, A. N., Harper, L., Schaier, M., Venning, M. C., Hamilton, P., Burst, V., Grundmann, F., Jadoul, M., Szombati, I., Tesař, V., Segelmark, M., Potarca, A., Schall, T. J., & Bekker, P. (2017). Randomized trial of c5a receptor inhibitor Avacopan in anca-associated vasculitis. Journal of the American Society of Nephrology, 28(9), 2756–2767. https://doi.org/10.1681/asn.2016111179
21. Jayne, D. R. W., Merkel, P. A., Schall, T. J., & Bekker, P. (2021). Avacopan for the treatment of anca-associated vasculitis. New England Journal of Medicine, 384(7), 599–609. https://doi.org/10.1056/nejmoa2023386
22. Jennette, J. C., Falk, R. J., Andrassy, K., Bacon, P. A., Churg, J., Gross, W. L., Hagen, E. C., Hoffman, G. S., Hunder, G. G., Kallenberg, C. G. M., Mccluskey, R. T., Sinico, R. A., Rees, A. J., Es, L. A. V., Waldherr, Rüd., & Wiik, A. (1994). Nomenclature of systemic vasculitides. Arthritis & Rheumatism, 37(2), 187–192. https://doi.org/10.1002/art.1780370206
23. Kaartinen, K., Safa, A., Kotha, S., Ratti, G., & Meri, S. (2019). Complement dysregulation in glomerulonephritis. Seminars in Immunology, 45, 101331. https://doi.org/10.1016/j.smim.2019.101331
24. Kimoto, Y., & Horiuchi, T. (2022a). The complement system and ANCA associated vasculitis in the era of anti-complement drugs. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.926044
25. Kimoto, Y., & Horiuchi, T. (2022b). The complement system and ANCA associated vasculitis in the era of anti-complement drugs. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.926044
26. Kitching, A. R., Anders, H.-J., Basu, N., Brouwer, E., Gordon, J., Jayne, D. R., Kullman, J., Lyons, P. A., Merkel, P. A., Savage, C. O. S., Specks, U., & Kain, R. (2020). ANCA-associated vasculitis. Nature Reviews Disease Primers, 6(1). https://doi.org/10.1038/s41572-020-0204-y
27. Kronbichler, A., Bajema, I. M., Bruchfeld, A., Mastroianni Kirsztajn, G., & Stone, J. H. (2024). Diagnosis and management of ANCA-associated vasculitis. The Lancet, 403(10427), 683–698. https://doi.org/10.1016/s0140-6736(23)01736-1
28. Lachmann, P. J., Lay, E., & Seilly, D. J. (2017). Experimental confirmation of the C3 tickover hypothesis by studies with an Ab (S77) that inhibits tickover in whole serum. The FASEB Journal, 32(1), 123–129. https://doi.org/10.1096/fj.201700734
29. Lucientes-Continente, L., Fernández-Juárez, G., Márquez-Tirado, B., Jiménez-Villegas, L., Acevedo, M., Cavero, T., Cámara, L. S., Draibe, J., Anton-Pampols, P., Caravaca-Fontán, F., Praga, M., Villacorta, J., & Goicoechea de Jorge, E. (2024). Complement alternative pathway determines disease susceptibility and severity in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. Kidney International, 105(1), 177–188. https://doi.org/10.1016/j.kint.2023.10.013
30. Marder, S. R., Chenoweth, D. E., Goldstein, I. M., & Perez, H. D. (1985). Chemotactic responses of human peripheral blood monocytes to the complement-derived peptides C5a and C5a des Arg. The Journal of Immunology, 134(5), 3325–3331. https://doi.org/10.4049/jimmunol.134.5.3325
31. Martin Merinero, H., Subías, M., Pereda, A., Gómez-Rubio, E., Juana Lopez, L., Fernandez, C., Goicoechea de Jorge, E., Martin-Santamaria, S., Cañada, F. J., & Rodríguez de Córdoba, S. (2021). Molecular bases for the association of FHR-1 with atypical hemolytic uremic syndrome and other diseases. Blood, 137(25), 3484–3494. https://doi.org/10.1182/blood.2020010069
32. Matola, A. T., Józsi, M., & Uzonyi, B. (2022). Overview on the role of complement-specific autoantibodies in diseases. Molecular Immunology, 151, 52–60. https://doi.org/10.1016/j.molimm.2022.08.011
33. Merkel, P. A., Niles, J., Jimenez, R., Spiera, R. F., Rovin, B. H., Bomback, A., Pagnoux, C., Potarca, A., Schall, T. J., & Bekker, P. (2020). Adjunctive treatment with Avacopan, an oral c5a receptor inhibitor, in patients with antineutrophil cytoplasmic antibody–associated vasculitis. ACR Open Rheumatology, 2(11), 662–671. https://doi.org/10.1002/acr2.11185
34. Merle, N. S., Church, S. E., Fremeaux-Bacchi, V., & Roumenina, L. T. (2015). Complement System Part I – Molecular Mechanisms of Activation and Regulation. Frontiers in Immunology, 6. https://doi.org/10.3389/fimmu.2015.00262
35. Moiseev, S., Lee, J., Zykova, A., Bulanov, N., Novikov, P., Gitel, E., Bulanova, M., Safonova, E., Shin, J., Kronbichler, A., & Jayne, D. R. W. (2020). The alternative complement pathway in ANCA-associated vasculitis: Further evidence and a meta-analysis. Authorea, Inc. http://dx.doi.org/10.22541/au.159231778.83521197
36. Mollnes, T. E., Storm, B. S., Brekke, O. L., Nilsson, P. H., & Lambris, J. D. (2022). Application of the C3 inhibitor compstatin in a human whole blood model designed for complement research – 20 years of experience and future perspectives. Seminars in Immunology, 59, 101604. https://doi.org/10.1016/j.smim.2022.101604
37. Monk, P. N., Scola, A., Madala, P., & Fairlie, D. P. (2007). Function, structure and therapeutic potential of complement C5a receptors. British Journal of Pharmacology, 152(4), 429–448. https://doi.org/10.1038/sj.bjp.0707332
38. Osman, M., Cohen Tervaert, J. W., & Pagnoux, C. (2021). Avacopan for the treatment of ANCA-associated vasculitis. Expert Review of Clinical Immunology, 17(7), 717–726. https://doi.org/10.1080/1744666x.2021.1932466
39. Papp, A., Papp, K., Uzonyi, B., Cserhalmi, M., Csincsi, Á. I., Szabó, Z., Bánlaki, Z., Ermert, D., Prohászka, Z., Erdei, A., Ferreira, V. P., Blom, A. M., & Józsi, M. (2022). Complement factor h-related proteins FHR1 and FHR5 interact with extracellular matrix ligands, reduce factor H regulatory activity and enhance complement activation. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.845953
40. Petr, V., & Thurman, J. M. (2023). The role of complement in kidney disease. Nature Reviews Nephrology, 19(12), 771–787. https://doi.org/10.1038/s41581-023-00766-1
41. Prendecki, M., & McAdoo, S. P. (2021). Targeting complement in ANCA-associated vasculitis: Insights from ADVOCATE. Nature Reviews Nephrology, 17(7), 439–440. https://doi.org/10.1038/s41581-021-00417-3
42. Rodriguezdecordoba, S. (2004). The human complement factor H: Functional roles, genetic variations and disease associations. Molecular Immunology, 41(4), 355–367. https://doi.org/10.1016/s0161-5890(04)00050-1
43. Serna, M., Giles, J. L., Morgan, B. P., & Bubeck, D. (2016). Structural basis of complement membrane attack complex formation. Nature Communications, 7(1). https://doi.org/10.1038/ncomms10587
44. Servais, A., Fremeaux-Bacchi, V., Lequintrec, M., Salomon, R., Blouin, J., Knebelmann, B., Grunfeld, J.-P., Lesavre, P., Noel, L.-H., & Fakhouri, F. (2006). Primary glomerulonephritis with isolated C3 deposits: A new entity which shares common genetic risk factors with haemolytic uraemic syndrome. Journal of Medical Genetics, 44(3), 193–199. https://doi.org/10.1136/jmg.2006.045328
45. Skerka, C., Pradel, G., Halder, L. D., Zipfel, P. F., Zipfel, S. L. H., & Strauß, O. (2020). Factor H‐related protein 1: A complement regulatory protein and guardian of necrotic‐type surfaces. British Journal of Pharmacology, 178(14), 2823–2831. https://doi.org/10.1111/bph.15290
46. Stokowska, A., Aswendt, M., Zucha, D., Lohmann, S., Wieters, F., Morán Suarez, J., Atkins, A. L., Li, Y., Miteva, M., Lewin, J., Wiedermann, D., Diedenhofen, M., Torinsson Naluai, Å., Abaffy, P., Valihrach, L., Kubista, M., Hoehn, M., Pekny, M., & Pekna, M. (2023). Complement C3a treatment accelerates recovery after stroke via modulation of astrocyte reactivity and cortical connectivity. Journal of Clinical Investigation, 133(10). https://doi.org/10.1172/jci162253
47. Strey, C. W., Markiewski, M., Mastellos, D., Tudoran, R., Spruce, L. A., Greenbaum, L. E., & Lambris, J. D. (2003). The proinflammatory mediators c3a and c5a are essential for liver regeneration. The Journal of Experimental Medicine, 198(6), 913–923. https://doi.org/10.1084/jem.20030374
48. Sun, X.-J., Li, Z.-Y., & Chen, M. (2023). Pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis. Rheumatology and Immunology Research, 4(1), 11–21. https://doi.org/10.2478/rir-2023-0003
49. Tampe, D., Baier, E., Hakroush, S., & Tampe, B. (2022). Comparative analysis of complement C3 and C4 serum levels for outcome prediction in ANCA-associated renal vasculitis. Journal of Nephrology, 36(1), 125–132. https://doi.org/10.1007/s40620-022-01414-w
50. Tesar, V., & Hruskova, Z. (2022). Complement inhibition in anca-associated vasculitis. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.888816
51. Trivioli, G., & Vaglio, A. (2020). The rise of complement in ANCA-associated vasculitis: From marginal player to target of modern therapy. Clinical and Experimental Immunology, 202(3), 403–406. https://doi.org/10.1111/cei.13515
52. Volanakis, J. E., Barnum, S. R., Giddens, M., & Galla, J. H. (1985). Renal filtration and catabolism of complement protein D. New England Journal of Medicine, 312(7), 395–399. https://doi.org/10.1056/nejm198502143120702
53. Watanabe-Kusunoki, K., & Anders, H.-J. (2024). Balancing efficacy and safety of complement inhibitors. Journal of Autoimmunity, 145, 103216. https://doi.org/10.1016/j.jaut.2024.103216
54. Wirthmueller, U., Dewald, B., Thelen, M., Schäfer, M. K., Stover, C., Whaley, K., North, J., Eggleton, P., Reid, K. B., & Schwaeble, W. J. (1997). Properdin, a positive regulator of complement activation, is released from secondary granules of stimulated peripheral blood neutrophils. The Journal of Immunology, 158(9), 4444–4451. https://doi.org/10.4049/jimmunol.158.9.4444
55. Xiao, H., Schreiber, A., Heeringa, P., Falk, R. J., & Jennette, J. C. (2007). Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies. The American Journal of Pathology, 170(1), 52–64. https://doi.org/10.2353/ajpath.2007.060573
56. Zhang, Y., Keenan, A., Dai, D.-F., May, K. S., Anderson, E. E., Lindorfer, M. A., Henrich, J. B., Pitcher, G. R., Taylor, R. P., & Smith, R. J. H. (2020). C3(H2O) prevents rescue of complement-mediated C3 glomerulopathy in Cfh–/– Cfd–/– mice. JCI Insight, 5(9). https://doi.org/10.1172/jci.insight.135758
57. Zipfel, P. F., & Skerka, C. (2009). Complement regulators and inhibitory proteins. Nature Reviews Immunology, 9(10), 729–740. https://doi.org/10.1038/nri2620
2. Boon, C. J. F., van de Kar, N. C., Klevering, B. J., Keunen, J. E. E., Cremers, F. P. M., Klaver, C. C. W., Hoyng, C. B., Daha, M. R., & den Hollander, A. I. (2009). The spectrum of phenotypes caused by variants in the CFH gene. Molecular Immunology, 46(8–9), 1573–1594. https://doi.org/10.1016/j.molimm.2009.02.013
3. Chen, M., Jayne, D. R. W., & Zhao, M.-H. (2017). Complement in ANCA-associated vasculitis: Mechanisms and implications for management. Nature Reviews Nephrology, 13(6), 359–367. https://doi.org/10.1038/nrneph.2017.37
4. Crnogorac, M., Horvatic, I., Kacinari, P., Ljubanovic, D. G., & Galesic, K. (2017). Serum C3 complement levels in ANCA associated vasculitis at diagnosis is a predictor of patient and renal outcome. Journal of Nephrology, 31(2), 257–262. https://doi.org/10.1007/s40620-017-0445-3
5. Csincsi, Á. I., Kopp, A., Zöldi, M., Bánlaki, Z., Uzonyi, B., Hebecker, M., Caesar, J. J. E., Pickering, M. C., Daigo, K., Hamakubo, T., Lea, S. M., Goicoechea de Jorge, E., & Józsi, M. (2015). Factor h–related protein 5 interacts with pentraxin 3 and the extracellular matrix and modulates complement activation. The Journal of Immunology, 194(10), 4963–4973. https://doi.org/10.4049/jimmunol.1403121
6. Csincsi, Á. I., Szabó, Z., Bánlaki, Z., Uzonyi, B., Cserhalmi, M., Kárpáti, É., Tortajada, A., Caesar, J. J. E., Prohászka, Z., Jokiranta, T. S., Lea, S. M., Rodríguez de Córdoba, S., & Józsi, M. (2017). FHR-1 binds to c-reactive protein and enhances rather than inhibits complement activation. The Journal of Immunology, 199(1), 292–303. https://doi.org/10.4049/jimmunol.1600483
7. de Boer, E. C., Thielen, A. J., Langereis, J. D., Kamp, A., Brouwer, M. C., Oskam, N., Jongsma, M. L., Baral, A. J., Spaapen, R. M., Zeerleder, S., Vidarsson, G., Rispens, T., Wouters, D., Pouw, R. B., & Jongerius, I. (2023). The contribution of the alternative pathway in complement activation on cell surfaces depends on the strength of classical pathway initiation. Clinical & Translational Immunology, 12(1). https://doi.org/10.1002/cti2.1436
8. Deshayes, S., Aouba, A., Khoy, K., Mariotte, D., Lobbedez, T., & Martin Silva, N. (2018). Hypocomplementemia is associated with worse renal survival in ANCA-positive granulomatosis with polyangiitis and microscopic polyangiitis. PLOS ONE, 13(4), e0195680. https://doi.org/10.1371/journal.pone.0195680
9. Goicoechea de Jorge, E., Caesar, J. J. E., Malik, T. H., Patel, M., Colledge, M., Johnson, S., Hakobyan, S., Morgan, B. P., Harris, C. L., Pickering, M. C., & Lea, S. M. (2013). Dimerization of complement factor H-related proteins modulates complement activation in vivo. Proceedings of the National Academy of Sciences, 110(12), 4685–4690. https://doi.org/10.1073/pnas.1219260110
10. Haas, M., & Eustace, J. A. (2004). Immune complex deposits in ANCA-associated crescentic glomerulonephritis: A study of 126 cases. Kidney International, 65(6), 2145–2152. https://doi.org/10.1111/j.1523-1755.2004.00632.x
11. Harboe, M., Ulvund, G., Vien, L., Fung, M., & Mollnes, T. E. (2004). The quantitative role of alternative pathway amplification in classical pathway induced terminal complement activation. Clinical and Experimental Immunology, 138(3), 439–446. https://doi.org/10.1111/j.1365-2249.2004.02627.x
12. Hebecker, M., & Józsi, M. (2012). Factor h-related protein 4 activates complement by serving as a platform for the assembly of alternative pathway C3 convertase via its interaction with c3b protein. Journal of Biological Chemistry, 287(23), 19528–19536. https://doi.org/10.1074/jbc.m112.364471
13. Hilhorst, M., van Paassen, P., van Rie, H., Bijnens, N., Heerings-Rewinkel, P., van Breda Vriesman, P., & Cohen Tervaert, J. W. (2015). Complement in ANCA-associated glomerulonephritis. Nephrology Dialysis Transplantation, 32(8), 1302–1313. https://doi.org/10.1093/ndt/gfv288
14. Hook, W. A., Snyderman, R., & Mergenhagen, S. E. (1970). Histamine-Releasing factor generated by the interaction of endotoxin with hamster serum. Infection and Immunity, 2(4), 462–467. https://doi.org/10.1128/iai.2.4.462-467.1970
15. Huugen, D., van Esch, A., Xiao, H., Peutz-Kootstra, C.-J., Buurman, W.-A., Tervaert, J. W. C., Jennette, J.-C., & Heeringa, P. (2007). Inhibition of complement factor C5 protects against anti-myeloperoxidase antibody-mediated glomerulonephritis in mice. Kidney International, 71(7), 646–654. https://doi.org/10.1038/sj.ki.5002103
16. Immunopathological studies of polyarteritis nodosa and wegener’s granulomatosis: A report of 43 patients with 51 renal biopsies. (1983). QJM: An International Journal of Medicine. https://doi.org/10.1093/oxfordjournals.qjmed.a067755
17. Irmscher, S., Brix, S. R., Zipfel, S. L. H., Halder, L. D., Mutlutürk, S., Wulf, S., Girdauskas, E., Reichenspurner, H., Stahl, R. A. K., Jungnickel, B., Wiech, T., Zipfel, P. F., & Skerka, C. (2019). Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-10766-0
18. Jayne, D. (2019). Complement inhibition in ANCA vasculitis. Néphrologie & Thérapeutique, 15(6), 409–412. https://doi.org/10.1016/j.nephro.2019.04.001
19. Jayne, D. (2021, March 28). 26 Lessons learned from complement inhibition in ANCA vasculitis. Abstracts. http://dx.doi.org/10.1136/lupus-2021-la.26
20. Jayne, D. R. W., Bruchfeld, A. N., Harper, L., Schaier, M., Venning, M. C., Hamilton, P., Burst, V., Grundmann, F., Jadoul, M., Szombati, I., Tesař, V., Segelmark, M., Potarca, A., Schall, T. J., & Bekker, P. (2017). Randomized trial of c5a receptor inhibitor Avacopan in anca-associated vasculitis. Journal of the American Society of Nephrology, 28(9), 2756–2767. https://doi.org/10.1681/asn.2016111179
21. Jayne, D. R. W., Merkel, P. A., Schall, T. J., & Bekker, P. (2021). Avacopan for the treatment of anca-associated vasculitis. New England Journal of Medicine, 384(7), 599–609. https://doi.org/10.1056/nejmoa2023386
22. Jennette, J. C., Falk, R. J., Andrassy, K., Bacon, P. A., Churg, J., Gross, W. L., Hagen, E. C., Hoffman, G. S., Hunder, G. G., Kallenberg, C. G. M., Mccluskey, R. T., Sinico, R. A., Rees, A. J., Es, L. A. V., Waldherr, Rüd., & Wiik, A. (1994). Nomenclature of systemic vasculitides. Arthritis & Rheumatism, 37(2), 187–192. https://doi.org/10.1002/art.1780370206
23. Kaartinen, K., Safa, A., Kotha, S., Ratti, G., & Meri, S. (2019). Complement dysregulation in glomerulonephritis. Seminars in Immunology, 45, 101331. https://doi.org/10.1016/j.smim.2019.101331
24. Kimoto, Y., & Horiuchi, T. (2022a). The complement system and ANCA associated vasculitis in the era of anti-complement drugs. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.926044
25. Kimoto, Y., & Horiuchi, T. (2022b). The complement system and ANCA associated vasculitis in the era of anti-complement drugs. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.926044
26. Kitching, A. R., Anders, H.-J., Basu, N., Brouwer, E., Gordon, J., Jayne, D. R., Kullman, J., Lyons, P. A., Merkel, P. A., Savage, C. O. S., Specks, U., & Kain, R. (2020). ANCA-associated vasculitis. Nature Reviews Disease Primers, 6(1). https://doi.org/10.1038/s41572-020-0204-y
27. Kronbichler, A., Bajema, I. M., Bruchfeld, A., Mastroianni Kirsztajn, G., & Stone, J. H. (2024). Diagnosis and management of ANCA-associated vasculitis. The Lancet, 403(10427), 683–698. https://doi.org/10.1016/s0140-6736(23)01736-1
28. Lachmann, P. J., Lay, E., & Seilly, D. J. (2017). Experimental confirmation of the C3 tickover hypothesis by studies with an Ab (S77) that inhibits tickover in whole serum. The FASEB Journal, 32(1), 123–129. https://doi.org/10.1096/fj.201700734
29. Lucientes-Continente, L., Fernández-Juárez, G., Márquez-Tirado, B., Jiménez-Villegas, L., Acevedo, M., Cavero, T., Cámara, L. S., Draibe, J., Anton-Pampols, P., Caravaca-Fontán, F., Praga, M., Villacorta, J., & Goicoechea de Jorge, E. (2024). Complement alternative pathway determines disease susceptibility and severity in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. Kidney International, 105(1), 177–188. https://doi.org/10.1016/j.kint.2023.10.013
30. Marder, S. R., Chenoweth, D. E., Goldstein, I. M., & Perez, H. D. (1985). Chemotactic responses of human peripheral blood monocytes to the complement-derived peptides C5a and C5a des Arg. The Journal of Immunology, 134(5), 3325–3331. https://doi.org/10.4049/jimmunol.134.5.3325
31. Martin Merinero, H., Subías, M., Pereda, A., Gómez-Rubio, E., Juana Lopez, L., Fernandez, C., Goicoechea de Jorge, E., Martin-Santamaria, S., Cañada, F. J., & Rodríguez de Córdoba, S. (2021). Molecular bases for the association of FHR-1 with atypical hemolytic uremic syndrome and other diseases. Blood, 137(25), 3484–3494. https://doi.org/10.1182/blood.2020010069
32. Matola, A. T., Józsi, M., & Uzonyi, B. (2022). Overview on the role of complement-specific autoantibodies in diseases. Molecular Immunology, 151, 52–60. https://doi.org/10.1016/j.molimm.2022.08.011
33. Merkel, P. A., Niles, J., Jimenez, R., Spiera, R. F., Rovin, B. H., Bomback, A., Pagnoux, C., Potarca, A., Schall, T. J., & Bekker, P. (2020). Adjunctive treatment with Avacopan, an oral c5a receptor inhibitor, in patients with antineutrophil cytoplasmic antibody–associated vasculitis. ACR Open Rheumatology, 2(11), 662–671. https://doi.org/10.1002/acr2.11185
34. Merle, N. S., Church, S. E., Fremeaux-Bacchi, V., & Roumenina, L. T. (2015). Complement System Part I – Molecular Mechanisms of Activation and Regulation. Frontiers in Immunology, 6. https://doi.org/10.3389/fimmu.2015.00262
35. Moiseev, S., Lee, J., Zykova, A., Bulanov, N., Novikov, P., Gitel, E., Bulanova, M., Safonova, E., Shin, J., Kronbichler, A., & Jayne, D. R. W. (2020). The alternative complement pathway in ANCA-associated vasculitis: Further evidence and a meta-analysis. Authorea, Inc. http://dx.doi.org/10.22541/au.159231778.83521197
36. Mollnes, T. E., Storm, B. S., Brekke, O. L., Nilsson, P. H., & Lambris, J. D. (2022). Application of the C3 inhibitor compstatin in a human whole blood model designed for complement research – 20 years of experience and future perspectives. Seminars in Immunology, 59, 101604. https://doi.org/10.1016/j.smim.2022.101604
37. Monk, P. N., Scola, A., Madala, P., & Fairlie, D. P. (2007). Function, structure and therapeutic potential of complement C5a receptors. British Journal of Pharmacology, 152(4), 429–448. https://doi.org/10.1038/sj.bjp.0707332
38. Osman, M., Cohen Tervaert, J. W., & Pagnoux, C. (2021). Avacopan for the treatment of ANCA-associated vasculitis. Expert Review of Clinical Immunology, 17(7), 717–726. https://doi.org/10.1080/1744666x.2021.1932466
39. Papp, A., Papp, K., Uzonyi, B., Cserhalmi, M., Csincsi, Á. I., Szabó, Z., Bánlaki, Z., Ermert, D., Prohászka, Z., Erdei, A., Ferreira, V. P., Blom, A. M., & Józsi, M. (2022). Complement factor h-related proteins FHR1 and FHR5 interact with extracellular matrix ligands, reduce factor H regulatory activity and enhance complement activation. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.845953
40. Petr, V., & Thurman, J. M. (2023). The role of complement in kidney disease. Nature Reviews Nephrology, 19(12), 771–787. https://doi.org/10.1038/s41581-023-00766-1
41. Prendecki, M., & McAdoo, S. P. (2021). Targeting complement in ANCA-associated vasculitis: Insights from ADVOCATE. Nature Reviews Nephrology, 17(7), 439–440. https://doi.org/10.1038/s41581-021-00417-3
42. Rodriguezdecordoba, S. (2004). The human complement factor H: Functional roles, genetic variations and disease associations. Molecular Immunology, 41(4), 355–367. https://doi.org/10.1016/s0161-5890(04)00050-1
43. Serna, M., Giles, J. L., Morgan, B. P., & Bubeck, D. (2016). Structural basis of complement membrane attack complex formation. Nature Communications, 7(1). https://doi.org/10.1038/ncomms10587
44. Servais, A., Fremeaux-Bacchi, V., Lequintrec, M., Salomon, R., Blouin, J., Knebelmann, B., Grunfeld, J.-P., Lesavre, P., Noel, L.-H., & Fakhouri, F. (2006). Primary glomerulonephritis with isolated C3 deposits: A new entity which shares common genetic risk factors with haemolytic uraemic syndrome. Journal of Medical Genetics, 44(3), 193–199. https://doi.org/10.1136/jmg.2006.045328
45. Skerka, C., Pradel, G., Halder, L. D., Zipfel, P. F., Zipfel, S. L. H., & Strauß, O. (2020). Factor H‐related protein 1: A complement regulatory protein and guardian of necrotic‐type surfaces. British Journal of Pharmacology, 178(14), 2823–2831. https://doi.org/10.1111/bph.15290
46. Stokowska, A., Aswendt, M., Zucha, D., Lohmann, S., Wieters, F., Morán Suarez, J., Atkins, A. L., Li, Y., Miteva, M., Lewin, J., Wiedermann, D., Diedenhofen, M., Torinsson Naluai, Å., Abaffy, P., Valihrach, L., Kubista, M., Hoehn, M., Pekny, M., & Pekna, M. (2023). Complement C3a treatment accelerates recovery after stroke via modulation of astrocyte reactivity and cortical connectivity. Journal of Clinical Investigation, 133(10). https://doi.org/10.1172/jci162253
47. Strey, C. W., Markiewski, M., Mastellos, D., Tudoran, R., Spruce, L. A., Greenbaum, L. E., & Lambris, J. D. (2003). The proinflammatory mediators c3a and c5a are essential for liver regeneration. The Journal of Experimental Medicine, 198(6), 913–923. https://doi.org/10.1084/jem.20030374
48. Sun, X.-J., Li, Z.-Y., & Chen, M. (2023). Pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis. Rheumatology and Immunology Research, 4(1), 11–21. https://doi.org/10.2478/rir-2023-0003
49. Tampe, D., Baier, E., Hakroush, S., & Tampe, B. (2022). Comparative analysis of complement C3 and C4 serum levels for outcome prediction in ANCA-associated renal vasculitis. Journal of Nephrology, 36(1), 125–132. https://doi.org/10.1007/s40620-022-01414-w
50. Tesar, V., & Hruskova, Z. (2022). Complement inhibition in anca-associated vasculitis. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.888816
51. Trivioli, G., & Vaglio, A. (2020). The rise of complement in ANCA-associated vasculitis: From marginal player to target of modern therapy. Clinical and Experimental Immunology, 202(3), 403–406. https://doi.org/10.1111/cei.13515
52. Volanakis, J. E., Barnum, S. R., Giddens, M., & Galla, J. H. (1985). Renal filtration and catabolism of complement protein D. New England Journal of Medicine, 312(7), 395–399. https://doi.org/10.1056/nejm198502143120702
53. Watanabe-Kusunoki, K., & Anders, H.-J. (2024). Balancing efficacy and safety of complement inhibitors. Journal of Autoimmunity, 145, 103216. https://doi.org/10.1016/j.jaut.2024.103216
54. Wirthmueller, U., Dewald, B., Thelen, M., Schäfer, M. K., Stover, C., Whaley, K., North, J., Eggleton, P., Reid, K. B., & Schwaeble, W. J. (1997). Properdin, a positive regulator of complement activation, is released from secondary granules of stimulated peripheral blood neutrophils. The Journal of Immunology, 158(9), 4444–4451. https://doi.org/10.4049/jimmunol.158.9.4444
55. Xiao, H., Schreiber, A., Heeringa, P., Falk, R. J., & Jennette, J. C. (2007). Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies. The American Journal of Pathology, 170(1), 52–64. https://doi.org/10.2353/ajpath.2007.060573
56. Zhang, Y., Keenan, A., Dai, D.-F., May, K. S., Anderson, E. E., Lindorfer, M. A., Henrich, J. B., Pitcher, G. R., Taylor, R. P., & Smith, R. J. H. (2020). C3(H2O) prevents rescue of complement-mediated C3 glomerulopathy in Cfh–/– Cfd–/– mice. JCI Insight, 5(9). https://doi.org/10.1172/jci.insight.135758
57. Zipfel, P. F., & Skerka, C. (2009). Complement regulators and inhibitory proteins. Nature Reviews Immunology, 9(10), 729–740. https://doi.org/10.1038/nri2620