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: 04 dec. 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
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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
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