Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Saint John on Patmos: Revelations of the Role of Antineutrophil Cytoplasmic Antibody (ANCA) in Vasculitis

Author(s): Esther N. Pijnappel, Ger T. Rijkers and Frans J. van Overveld*

Volume 27, Issue 17, 2020

Page: [2852 - 2862] Pages: 11

DOI: 10.2174/0929867327666191213112220

Price: $65

conference banner
Abstract

Diagnosis of vasculitis is based on the presence of histologic features and serological testing for antineutrophil cytoplasmic antibodies (ANCA). In patients with vasculitis, two types of ANCA have been identified: ANCA directed against the neutrophil serine protease proteinase-3 (PR3) which results in a cytoplasmic immunofluorescence pattern (c-ANCA) and ANCA directed against the neutrophil enzyme myeloperoxidase (MPO), which results in a perinuclear immunofluorescence pattern (p-ANCA). Question is if the presence of ANCA is the consequence of abnormal neutrophil adhesion, activation, and apoptosis. Or is it, through mechanisms which are not totally clear for the moment, the cause of vasculitis. In the latter case it has to be postulated that ANCA autoantigens are expressed on the cell surface of viable, or activated, or early-apoptotic neutrophils.

Keywords: Antineutrophil cytoplasmic antibodies (ANCA), myeloperoxidase (MPO), neutrophils, polyangiitis, proteinase-3 (PR3), immunofluorescence pattern (p-ANCA), vasculitis, antineutrophil cytoplasmic antibodies, cytoplasmic immunofluorescence pattern (c-ANCA).

« Previous Next »
[1]
Cupps, T.R.; Fauci, A.S. The vasculitic syndromes. Adv. Intern. Med., 1982, 27, 315-344.
[PMID: 6122351]
[2]
Collins, T.R. Diagnostic criteria, classification lacking for vasculitis; new research in treatment for systemic sclerosis; The Rheumatologist, 2016.
[3]
Freeman, S. New ACR-EULAR diagnostic criteria proposed for ANCA-associated vasculitides; Vus. Spec, 2017.
[4]
Luqmani, P.M.; Watts, R. In: ; New classification criteria for ANCA-associated vasculitis: implications for clinical practice, ACR/ARHP Annual Meeting, Washington, DC, USA, November. , 2016.
[5]
DCVAS Diagnostic and classification of the systemic vasculitides., 2018.
[6]
Bossuyt, X.; Cohen Tervaert, J.W.; Arimura, Y.; Blockmans, D.; Flores-Suárez, L.F.; Guillevin, L.; Hellmich, B.; Jayne, D.; Jennette, J.C.; Kallenberg, C.G.M.; Moiseev, S.; Novikov, P.; Radice, A.; Savige, J.A.; Sinico, R.A.; Specks, U.; van Paassen, P.; Zhao, M.H.; Rasmussen, N.; Damoiseaux, J.; Csernok, E. Position paper: Revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis. Nat. Rev. Rheumatol., 2017, 13(11), 683-692.
[http://dx.doi.org/10.1038/nrrheum.2017.140] [PMID: 28905856]
[7]
Tervaert, J.W.; Goldschmeding, R.; Elema, J.D.; van der Giessen, M.; Huitema, M.G.; van der Hem, G.K.; The, T.H.; von dem Borne, A.E.; Kallenberg, C.G. Autoantibodies against myeloid lysosomal enzymes in crescentic glomerulonephritis. Kidney Int., 1990, 37(2), 799-806.
[http://dx.doi.org/10.1038/ki.1990.48] [PMID: 2155342]
[8]
Tervaert, J.W.; van der Woude, F.J.; Fauci, A.S.; Ambrus, J.L.; Velosa, J.; Keane, W.F.; Meijer, S.; van der Giessen, M.; van der Hem, G.K.; The, T.H. Association between active Wegener’s granulomatosis and anticytoplasmic antibodies. Arch. Intern. Med., 1989, 149(11), 2461-2465.
[http://dx.doi.org/10.1001/archinte.1989.00390110055012] [PMID: 2684074]
[9]
Savige, J.; Davies, D.; Falk, R.J.; Jennette, J.C.; Wiik, A. Antineutrophil cytoplasmic antibodies and associated diseases: a review of the clinical and laboratory features. Kidney Int., 2000, 57(3), 846-862.
[http://dx.doi.org/10.1046/j.1523-1755.2000.057003846.x] [PMID: 10720938]
[10]
Gabillet, J.; Millet, A.; Pederzoli-Ribeil, M.; Tacnet-Delorme, P.; Guillevin, L.; Mouthon, L.; Frachet, P.; Witko-Sarsat, V. Proteinase 3, the autoantigen in granulomatosis with polyangiitis, associates with calreticulin on apoptotic neutrophils, impairs macrophage phagocytosis, and promotes inflammation. J. Immunol., 2012, 189(5), 2574-2583.
[http://dx.doi.org/10.4049/jimmunol.1200600] [PMID: 22844112]
[11]
Kuckleburg, C.J.; Tilkens, S.B.; Santoso, S.; Newman, P.J. Proteinase 3 contributes to transendothelial migration of NB1-positive neutrophils. J. Immunol., 2012, 188(5), 2419-2426.
[http://dx.doi.org/10.4049/jimmunol.1102540] [PMID: 22266279]
[12]
von Vietinghoff, S.; Eulenberg, C.; Wellner, M.; Luft, F.C.; Kettritz, R. Neutrophil surface presentation of the anti-neutrophil cytoplasmic antibody-antigen proteinase 3 depends on N-terminal processing. Clin. Exp. Immunol., 2008, 152(3), 508-516.
[http://dx.doi.org/10.1111/j.1365-2249.2008.03663.x] [PMID: 18462208]
[13]
Kantari, C.; Pederzoli-Ribeil, M.; Amir-Moazami, O.; Gausson-Dorey, V.; Moura, I.C.; Lecomte, M.C.; Benhamou, M.; Witko-Sarsat, V. Proteinase 3, the Wegener autoantigen, is externalized during neutrophil apoptosis: evidence for a functional association with phospholipid scramblase 1 and interference with macrophage phagocytosis. Blood, 2007, 110(12), 4086-4095.
[http://dx.doi.org/10.1182/blood-2007-03-080457] [PMID: 17712045]
[14]
Gardai, S.J.; McPhillips, K.A.; Frasch, S.C.; Janssen, W.J.; Starefeldt, A.; Murphy-Ullrich, J.E.; Bratton, D.L.; Oldenborg, P.A.; Michalak, M.; Henson, P.M. Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte. Cell, 2005, 123(2), 321-334.
[http://dx.doi.org/10.1016/j.cell.2005.08.032] [PMID: 16239148]
[15]
Segawa, K.; Kurata, S.; Yanagihashi, Y.; Brummelkamp, T.R.; Matsuda, F.; Nagata, S. Caspase-mediated cleavage of phospholipid flippase for apoptotic phosphatidylserine exposure. Science, 2014, 344(6188), 1164-1168.
[http://dx.doi.org/10.1126/science.1252809] [PMID: 24904167]
[16]
Lentz, B.R. Exposure of platelet membrane phosphatidylserine regulates blood coagulation. Prog. Lipid Res., 2003, 42(5), 423-438.
[http://dx.doi.org/10.1016/S0163-7827(03)00025-0] [PMID: 12814644]
[17]
Gold, L.I.; Eggleton, P.; Sweetwyne, M.T.; Van Duyn, L.B.; Greives, M.R.; Naylor, S.M.; Michalak, M.; Murphy-Ullrich, J.E. Calreticulin: non-endoplasmic reticulum functions in physiology and disease. FASEB J., 2010, 24(3), 665-683.
[http://dx.doi.org/10.1096/fj.09-145482] [PMID: 19940256]
[18]
Michalak, M.; Groenendyk, J.; Szabo, E.; Gold, L.I.; Opas, M. Calreticulin, a multi-process calcium-buffering chaperone of the endoplasmic reticulum. Biochem. J., 2009, 417(3), 651-666.
[http://dx.doi.org/10.1042/BJ20081847] [PMID: 19133842]
[19]
Savill, J.S.; Wyllie, A.H.; Henson, J.E.; Walport, M.J.; Henson, P.M.; Haslett, C. Macrophage phagocytosis of aging neutrophils in inflammation. Programmed cell death in the neutrophil leads to its recognition by macrophages. J. Clin. Invest., 1989, 83(3), 865-875.
[http://dx.doi.org/10.1172/JCI113970] [PMID: 2921324]
[20]
Novick, D.; Rubinstein, M.; Azam, T.; Rabinkov, A.; Dinarello, C.A.; Kim, S.H. Proteinase 3 is an IL-32 binding protein. Proc. Natl. Acad. Sci. USA, 2006, 103(9), 3316-3321.
[http://dx.doi.org/10.1073/pnas.0511206103] [PMID: 16488976]
[21]
Bae, S.; Kim, Y.G.; Choi, J.; Hong, J.; Lee, S.; Kang, T.; Jeon, H.; Hong, K.; Kim, E.; Kwak, A.; Lee, C.K.; Yoo, B.; Park, Y.B.; Song, E.Y.; Kim, S. Elevated interleukin-32 expression in granulomatosis with polyangiitis. Rheumatology (Oxford), 2012, 51(11), 1979-1988.
[http://dx.doi.org/10.1093/rheumatology/kes163] [PMID: 22850185]
[22]
Khawar, M.B.; Mukhtar, M.; Abbasi, M.H.; Sheikh, N. IL-32θ: a recently identified anti-inflammatory variant of IL-32 and its preventive role in various disorders and tumor suppressor activity. Am. J. Transl. Res., 2017, 9(11), 4726-4737.
[PMID: 29218075]
[23]
Son, D.J.; Jung, Y.Y.; Seo, Y.S.; Park, H.; Lee, D.H.; Kim, S.; Roh, Y.S.; Han, S.B.; Yoon, D.Y.; Hong, J.T. Interleukin-32alpha inhibits endothelial inflammation, vascular smooth muscle cell activation, and atherosclerosis by upregulating Timp3 and Reck through suppressing microRNA-205 biogenesis. Theranostics, 2017, 7(8), 2186-2203.
[http://dx.doi.org/10.7150/thno.18407] [PMID: 28740544]
[24]
Korkmaz, B.; Lesner, A.; Letast, S.; Mahdi, Y.K.; Jourdan, M.L.; Dallet-Choisy, S.; Marchand-Adam, S.; Kellenberger, C.; Viaud-Massuard, M.C.; Jenne, D.E.; Gauthier, F. Neutrophil proteinase 3 and dipeptidyl peptidase I (cathepsin C) as pharmacological targets in granulomatosis with polyangiitis (Wegener granulomatosis). Semin. Immunopathol., 2013, 35(4), 411-421.
[http://dx.doi.org/10.1007/s00281-013-0362-z] [PMID: 23385856]
[25]
Turk, D.; Janjić, V.; Stern, I.; Podobnik, M.; Lamba, D.; Dahl, S.W.; Lauritzen, C.; Pedersen, J.; Turk, V.; Turk, B. Structure of human dipeptidyl peptidase I (cathepsin C): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases. EMBO J., 2001, 20(23), 6570-6582.
[http://dx.doi.org/10.1093/emboj/20.23.6570] [PMID: 11726493]
[26]
Zimmer, M.; Medcalf, R.L.; Fink, T.M.; Mattmann, C.; Lichter, P.; Jenne, D.E. Three human elastase-like genes coordinately expressed in the myelomonocyte lineage are organized as a single genetic locus on 19pter. Proc. Natl. Acad. Sci. USA, 1992, 89(17), 8215-8219.
[http://dx.doi.org/10.1073/pnas.89.17.8215] [PMID: 1518849]
[27]
Garwicz, D.; Lennartsson, A.; Jacobsen, S.E.; Gullberg, U.; Lindmark, A. Biosynthetic profiles of neutrophil serine proteases in a human bone marrow-derived cellular myeloid differentiation model. Haematologica, 2005, 90(1), 38-44.
[PMID: 15642667]
[28]
Rao, N.V.; Rao, G.V.; Marshall, B.C.; Hoidal, J.R. Biosynthesis and processing of proteinase 3 in U937 cells. Processing pathways are distinct from those of cathepsin G. J. Biol. Chem., 1996, 271(6), 2972-2978.
[http://dx.doi.org/10.1074/jbc.271.6.2972] [PMID: 8621689]
[29]
Matsumoto, T.; Kaneko, T.; Seto, M.; Wada, H.; Kobayashi, T.; Nakatani, K.; Tonomura, H.; Tono, Y.; Ohyabu, M.; Nobori, T.; Shiku, H.; Sudo, A.; Uchida, A.; Kurosawa, D.J.; Kurosawa, S. The membrane proteinase 3 expression on neutrophils was downregulated after treatment with infliximab in patients with rheumatoid arthritis. Clin. Appl. Thromb. Hemost., 2008, 14(2), 186-192.
[http://dx.doi.org/10.1177/1076029607303961] [PMID: 18372277]
[30]
Yates, M.; Watts, R.A.; Bajema, I.M.; Cid, M.C.; Crestani, B.; Hauser, T.; Hellmich, B.; Holle, J.U.; Laudien, M.; Little, M.A.; Luqmani, R.A.; Mahr, A.; Merkel, P.A.; Mills, J.; Mooney, J.; Segelmark, M.; Tesar, V.; Westman, K.; Vaglio, A.; Yalçındağ, N.; Jayne, D.R.; Mukhtyar, C. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann. Rheum. Dis., 2016, 75(9), 1583-1594.
[http://dx.doi.org/10.1136/annrheumdis-2016-209133] [PMID: 27338776]
[31]
Falk, R.J.; Terrell, R.S.; Charles, L.A.; Jennette, J.C. Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. Proc. Natl. Acad. Sci. USA, 1990, 87(11), 4115-4119.
[http://dx.doi.org/10.1073/pnas.87.11.4115] [PMID: 2161532]
[32]
Ralston, D.R.; Marsh, C.B.; Lowe, M.P.; Wewers, M.D. Antineutrophil cytoplasmic antibodies induce monocyte IL-8 release. Role of surface proteinase-3, alpha1-antitrypsin, and Fcgamma receptors. J. Clin. Invest., 1997, 100(6), 1416-1424.
[http://dx.doi.org/10.1172/JCI119662] [PMID: 9294107]
[33]
Remold-O’Donnell, E.; Nixon, J.C.; Rose, R.M. Elastase inhibitor. Characterization of the human elastase inhibitor molecule associated with monocytes, macrophages, and neutrophils. J. Exp. Med., 1989, 169(3), 1071-1086.
[http://dx.doi.org/10.1084/jem.169.3.1071] [PMID: 2926322]
[34]
Cooley, J.; Takayama, T.K.; Shapiro, S.D.; Schechter, N.M.; Remold-O’Donnell, E. The serpin MNEI inhibits elastase-like and chymotrypsin-like serine proteases through efficient reactions at two active sites. Biochemistry, 2001, 40(51), 15762-15770.
[http://dx.doi.org/10.1021/bi0113925] [PMID: 11747453]
[35]
Schreiber, A.; Busjahn, A.; Luft, F.C.; Kettritz, R. Membrane expression of proteinase 3 is genetically determined. J. Am. Soc. Nephrol., 2003, 14(1), 68-75.
[http://dx.doi.org/10.1097/01.ASN.0000040751.83734.D1] [PMID: 12506139]
[36]
McKinney, E.F.; Willcocks, L.C.; Broecker, V.; Smith, K.G. The immunopathology of ANCA-associated vasculitis. Semin. Immunopathol., 2014, 36(4), 461-478.
[http://dx.doi.org/10.1007/s00281-014-0436-6] [PMID: 25056155]
[37]
Lyons, P.A.; Rayner, T.F.; Trivedi, S.; Holle, J.U.; Watts, R.A.; Jayne, D.R.; Baslund, B.; Brenchley, P.; Bruchfeld, A.; Chaudhry, A.N.; Cohen Tervaert, J.W.; Deloukas, P.; Feighery, C.; Gross, W.L.; Guillevin, L.; Gunnarsson, I.; Harper, L.; Hrušková, Z.; Little, M.A.; Martorana, D.; Neumann, T.; Ohlsson, S.; Padmanabhan, S.; Pusey, C.D.; Salama, A.D.; Sanders, J.S.; Savage, C.O.; Segelmark, M.; Stegeman, C.A.; Tesař, V.; Vaglio, A.; Wieczorek, S.; Wilde, B.; Zwerina, J.; Rees, A.J.; Clayton, D.G.; Smith, K.G. Genetically distinct subsets within ANCA-associated vasculitis. N. Engl. J. Med., 2012, 367(3), 214-223.
[http://dx.doi.org/10.1056/NEJMoa1108735] [PMID: 22808956]
[38]
Mohammad, A.; Segelmark, M. Primary systemic vasculitis with severe α1-antitrypsin deficiency revisited. Scand. J. Rheumatol., 2014, 43(3), 242-245.
[http://dx.doi.org/10.3109/03009742.2013.846405] [PMID: 24313382]
[39]
Voorzaat, B.M.; van Schaik, J.; Crobach, S.L.; van Rijswijk, C.S.; Rotmans, J.I. Alpha-1 antitrypsin deficiency presenting with MPO-ANCA associated vasculitis and aortic dissection. Case Rep. Med., 2017, 2017 8140641
[http://dx.doi.org/10.1155/2017/8140641] [PMID: 28367219]
[40]
Rooney, C.P.; Taggart, C.; Coakley, R.; McElvaney, N.G.; O’Neill, S.J. Anti-proteinase 3 antibody activation of neutrophils can be inhibited by alpha1-antitrypsin. Am. J. Respir. Cell Mol. Biol., 2001, 24(6), 747-754.
[http://dx.doi.org/10.1165/ajrcmb.24.6.4147] [PMID: 11415941]
[41]
Surmiak, M.; Sanak, M. Different forms of alpha-1 antitrypsin and neutrophil activation mediated by human anti-PR3 IgG antibodies. Pharmacol. Rep., 2016, 68(6), 1276-1284.
[http://dx.doi.org/10.1016/j.pharep.2016.08.003] [PMID: 27689755]
[42]
Mota, A.; Sahebghadam Lotfi, A.; Jamshidi, A.R.; Najavand, S. Alpha 1-antitrypsin activity is markedly decreased in Wegener’s granulomatosis. Rheumatol. Int., 2014, 34(4), 553-558.
[http://dx.doi.org/10.1007/s00296-013-2745-9] [PMID: 23604680]
[43]
Kallenberg, C.G. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis: where to go? Clin. Exp. Immunol., 2011, 164(Suppl. 1), 1-3.
[http://dx.doi.org/10.1111/j.1365-2249.2011.04355.x] [PMID: 21447120]
[44]
Kain, R.; Exner, M.; Brandes, R.; Ziebermayr, R.; Cunningham, D.; Alderson, C.A.; Davidovits, A.; Raab, I.; Jahn, R.; Ashour, O.; Spitzauer, S.; Sunder-Plassmann, G.; Fukuda, M.; Klemm, P.; Rees, A.J.; Kerjaschki, D. Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis. Nat. Med., 2008, 14(10), 1088-1096.
[http://dx.doi.org/10.1038/nm.1874] [PMID: 18836458]
[45]
Popa, E.R.; Stegeman, C.A.; Kallenberg, C.G.; Tervaert, J.W. Staphylococcus aureus and Wegener’s granulomatosis. Arthritis Res., 2002, 4(2), 77-79.
[http://dx.doi.org/10.1186/ar392] [PMID: 11879541]
[46]
Bonert, M. File: Wegener's granulomatosis - very high mag.jpg. 2019..Available at:. https://commons.wikimedia. org/wiki/File:Wegener%27s_granulomatosis_-_very_high_mag.jpg (Accessed Date: November 2019).

Rights & Permissions Print Cite
Article Metrics
6
1
© 2024 Bentham Science Publishers | Privacy Policy