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© Borgis - Postępy Nauk Medycznych 9/2016, s. 664-668
*Maciej Szymczak, Marian Klinger
ANCA associated vasculitis – new insight into pathogenesis, diagnostics and therapy**
Nowe spojrzenie na patogenezę, diagnostykę i leczenie układowego zapalenia naczyń związanego z przeciwciałami ANCA
Department of Nephrology and Transplantation Medicine, Wrocław Medical University
Head of Department: Professor Marian Klinger MD, PhD
Streszczenie
Układowe zapalenie naczyń związane z przeciwciałami ANCA to jedno z ważniejszych układowych zapaleń naczyń. Częstość tego zapalenia wzrasta w ostatnich latach. W patogenezie tej choroby biorą udział zarówno czynniki genetyczne, jak i środowiskowe. Niekontrolowana aktywacja granulocytów obojętnochłonnych prowadzi do ciągu immunologicznych procesów skutkujących zapaleniem naczyń. Zaawansowana niewydolność nerek, stwardnienie i zmiany zanikowe w biopsji nerki to czynniki ryzyka rozwoju schyłkowej niewydolności nerek. Szybka diagnoza i wykonanie biopsji nerki są ważne we właściwym zaplanowaniu procesu leczniczego. Jest wiele schematów terapeutycznych stosowanych w leczeniu tej choroby. Standardowe schematy z użyciem steroidów i cyklofosfamidu w indukcji remisji i steroidów z azatiopryną w leczeniu podtrzymującym są zamieniane w pewnych przypadkach przez nowsze schematy z użyciem rituksimabu. Wszystkie te schematy są obarczone jednak ryzykiem działań niepożądanych. W związku z tym istotne jest ścisłe monitorowanie leczenia i właściwy wybór dawek leków dla poszczególnych pacjentów, aby uchronić pacjentów przed możliwymi powikłaniami leczenia i nawrotami choroby.
Summary
ANCA (anti-neutrophil cytoplasmic antibodies) associated vasculitis is common kind of vasculitis. Frequency of this vasculitis increases last years. Both genetic and environmental factors are involved in the pathogenesis of this disease. Uncontrolled neutrophils activation leads to cascade of immunological processes resulting in the vasculitis development. Advanced kidney injury, sclerotic and atrophic changes in kidney biopsy specimens are the risk factors of end-stage renal disease development. Fast diagnosis and kidney biopsy performance are important to plan proper therapeutic scheme. There are many therapeutic regimens used to treat this kind of disease. Standard regimens with steroids and cyclophosphamide in induction remission, and steroids with azathioprine as a maintenance therapy are replaced in some cases by newer schemes with rituximab usage. However all these regimens are connected with adverse effects and there is a need of accurate treatment monitoring and reasonable assessment of the drugs doses for specific patients to protect patients against complications and relapses.
Introduction
ANCA (anti-neutrophil cytoplasmic antibodies) associated vasculitis is according to Chapel-Hill Consensus necrotizing vasculitis, vasculitis with few or no immune deposits, predominantly affecting small vessels (i.e. capillaries, venules, arterioles and small arteries), that is associated with MPO (myeloperoxidase)-ANCA or PR3 (proteinase3)-ANCA. These kinds of antibodies are connected with three types of vasculitis: granulomatosis with polyangiitis-GPA (earlier Wegener’s granulomatosis), microscopic vasculitis-MPA and eosinophilic granulomatosis with polyangiitis-EGPA (earlier Churg-Strauss syndrome) (1). This review summarizes current information about ANCA associated vasculitis concerning epidemiology, pathogenesis, diagnostics and therapy.
Epidemiology of vasculitis
Vasculitis type depends on geographical region. Granulomatosis with polyangiitis is more frequent in the northern Europe. Microscopic vasculitis is more common in southern Europe, Japan (2) and in Peru (3), Asians and Maoris in New Zealand (4). Granulomatosis with polyangiitis frequency doubled in Germany between 1994 and 2006. The reasons were probably: increase of disease awareness and more often diagnosis of this disease, increase in survival of patients (5). Frequency of microscopic polyangiitis also increases in Germany (5), Australia (6). The frequency of biopsy proven ANCA (+) vasculitis among people over 18 years old was more than 13.2 million per year. 36 from 82 patients (44%) have died for 12 years of observation (7).
Etiology
There are many antigens associated with susceptibility to ANCA associated vasculitis. Full list of them may be found in one of the newest publications (8). Very important are also environmental factors, especially infections. Associations between infections: Pseudomonas, Klebsiella, Escherichia coli (9), Staphylococcus aureus (10), Enterococcus (11), Ross-River virus (12), Epstein-Barr virus (13), exposure to mRNA in influenza vaccine (14), Rickettsiae (15) infections and development of ANCA associated vasculitis in human were found. Molecular mimicry between fimbrie FimH of Escherichia coli, Klebsiella and human LAMP (lysosome associated membrane protein) antibodies was also described (16). There was also found that granulomatosis with polyangiitis appearance is cyclical with a period 7.6 years. There was suggested that this disease might be connected with cyclical infection (17). Connections between ambient UVR (ultraviolet radiation) and incidence of granulomatosis with polyangiitis and eosynophilic granulomatosis with polyangiitis were also found (18). Silica is other postulated risk factor of granulomatosis with polyangiitis and microscopic vasculitis (19). Other potential risk factors of c-ANCA positive vasculitis are heavy metal and pesticides exposure, atopy (20), farm exposure (21), drugs. There was also found that microscopic vasculitis is more common in rural than in urban area in Australia (6).
ANCA associated vasculitis pathogenesis
ANCA associated vasculitis accordingly with current knowledge develops as a result of neutrophils activation by autoantibodies directed to neutrophils antigens myeloperoxidase and proteinase 3 or against human lysosome-associated membrane protein-2 which is present in neutrophils and vascular endothelium (22). Genetic background promotes development of the disease. At the beginning many environmental factors (infections, stress, lipopolisaccharides and others) may cause priming of neutrophils and complement system activation. As a result of epigenetic changes primed neutrophils exhibit more than normal myeloperoxidase and proteinase 3 on their surface (23) and adhere to endothelium. After that production of ANCA antibodies begins. ANCA antibodies increase priming of neutrophils through Fab and Fc receptor. Primed neutrophils excrete many factors like properdine, B factor, proteases, ROS (reactive oxygen species) and myeloperoxidase. Indicators of neutrophils apoptosis were diminished in the course of ANCA positive systemic vasculitis in comparison with healthy persons (24). As a result vascular endothelium dysfunction appears and alternative complement pathway activation begins including C5a production (25). C5a strongly attracts neutrophils what cause an influx of this kind of cells and induction of severe necrotic vasculitis (26). Moreover in the course of ANCA vasculitis development of NETs (neutrophil extracellular traps) formation appears (27). Products of granulocytes priming especially free radicals promote NETs formation (28). NETs may bind different antigens in chromatin web and activate TLRs (Toll-like receptors) directly (29). TLRs activate lymphocytes Th: TLR9-Th1, and TLR2-Th17 (30). Treg cells function is also impaired in the course of ANCA vasculitis (31). Breg number is diminished without impaired function (in terms of Il-10 production) in the course of ANCA associated vasculitis (32). There is a large number of memory B cells relatively to other B cells during remission in patients with ANCA associated vasculitis. This imbalance may promote big percentage of disease relapses, especially in PR-3 ANCA systemic vasculitis (33). Changes in other kinds of cells function in the course of ANCA associated vasculitis also appear. There was also found that serum from patients with ANCA (+) vasculitis stimulates M2c macrophages podtype to fagocytosis (34). CD14 expression correlated with ANCA autoantigen expression in ANCA vasculitis on monocytes and there were suggestions that it may reflect cell activation (35). Macrophages and dendritic cells were the cells producing chemokine CCL18, antigen that expression is high in crescentic ANCA associated vasculitis and correlates with crescent formation, interstitial inflammation, and impairment of renal function (36). The biomarkers of ANCA positive systemic vasculitis in urine are also searched. It was found that in the course of the disease relapses: alfa-1 acid glycoprotein, KIM-1 (kidney injury molecule 1), MCP-1 (monocyte chemoattractant protein-1), NGAL (neutrophil gelatinase-associated lipocalin) levels increased. MCP-1 levels were the best differentiator of active disease and remission: 1.3 fold increase of MCP-1 was highly associated with relapse of disease (94% sensitivity and 89% of specificity) (37).
Diagnosis

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Piśmiennictwo
Jennette JC: Overview of the 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Clin Exp Nephrol 2013 Oct; 17(5): 603-606.
Scott DG, Watts RA: Epidemiology and clinical features of systemic vasculitis. Clin Exp Nephrol 2013; 17(5): 607-610.
Sánchez Torres A, Acevedo Vásquez E, Sánchez Schwartz C et al.: Epidemiología de las vasculitis sistèmicas primarias en una población latinoamericana. Reumatologia 2005; 21: 145-150.
O’Donnell JL, Stevanovic VR, Frampton C et al.: Wegener’s granulomatosis in New Zealand: evidence for a latitude-dependent incidence gradient. Intern Med J 2007; 37: 242-246.
Herlyn K, Buckert F, Gross WL, Reinhold-Keller E: Doubled prevalence rates of ANCA-associated vasculitides and giant cell arteritis between 1994 and 2006 in northern Germany. Rheumatology (Oxford) 2014; 53(5): 882-889.
Ormerod AS, Cook MC: Epidemiology of primary systemic vasculitis in the Australian Capital Territory and south-eastern New South Wales. Intern Med J 2008; 38: 816-823.
Mohammad AJ, Weiner M, Sjöwall C et al.: Incidence and disease severity of anti-neutrophil cytoplasmic antibody-associated nephritis are higher than in lupus nephritis in Sweden. Nephrol Dial Transplant 2015; 30S1: i23-30.
Alberici F, Martorana D, Vaglio A: Genetic aspects of anti-neutrophil cytoplasmic antibody-associated vasculitis. Nephrol Dial Transplant 2015; 30: i37-45.
Savige J, Pollock W, Trevisin M: What do antineutrophil cytoplasmic antibodies (ANCA) tell us? Best Pract Res Clin Rheumatol 2005; 19: 263-276.
Stegeman CA, Tervaert JW, Sluiter WJ et al.: Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis. Ann Intern Med 1994; 120: 12-17.
Fukasawa H, Hayashi M, Kinoshita N et al.: Rapidly progressive glomerulonephritis associated with PR3-ANCA positive subacute bacterial endocarditis. Intern Med 2012; 51: 2587-2590.
Davies DJ, Moran JE, Niall JF et al.: Segmental necrotizing glomerulonephritis with antineutrophil antibody: possible arbovirus aetiology? Br Med J (Clin Res Ed)1982; 285: 606.
Xu P, Lin S, Wei L et al.: Antineutrophil cytoplasmic antibody-associated vasculitis associated with Epstein-Barr virus infection: a case report and review of the literature. Infection 2014; 42: 591-594.
Jeffs LS, Nitschke J, Tervaert JW et al.: Viral RNA in the influenza vaccine may have contributed to the development of ANCA-associated vasculitis in a patient following immunisation. Clin Rheumatol 2016; 35(4): 943-951.
Nickerson A, Marik PE: Life-threatening ANCA-positive vasculitis associated with rickettsial infection. BMJ Case Rep 2012; 2012: pii: bcr0320125993. DOI: 10.1136/bcr.03.2012.5993.
Kain R, Exner M, Brandes R et al.: Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis. Nat Med 2008; 14: 1088-1096.
Watts RA, Mooney J, Skinner J et al.: The contrasting epidemiology of granulomatosis with polyangiitis (Wegener’s) and microscopic polyangiitis. Rheumatology 2012; 51: 926-931.
Gatenby PA, Lucas RM, Engelsen O et al.: Antineutrophil cytoplasmic antibody-associated vasculitides: could geographic patterns be explained by ambient ultraviolet radiation? Arthritis Rheum 2009; 61: 1417-1424.
Mahr A, Artigues N, Coste J et al.: Seasonal variations in onset of Wegener’s granulomatosis: increased in summer? J Rheumatol 2006; 33: 1615-1622.
De Lind van Wijngaarden RA, van Rijn L, Hagen EC et al.: Hypotheses on the etiology of antineutrophil cytoplasmic autoantibody associated vasculitis: the cause is hidden, but the result is known. Clin J Am Soc Nephrol 2008; 3: 237-252.
Willeke P, Schlüter B, Sauerland C et al.: Farm Exposure as a Differential Risk Factor in ANCA-Associated Vasculitis. PLoS One 2015; 10(9): e0137196.
Pendergraft WF 3rd, Cortazar FB, Wenger J et al.: Long-term maintenance therapy using rituximab-induced continuous B-cell depletion in patients with ANCA vasculitis. Clin J Am Soc Nephrol 2014; 9(4): 736-744.
Ciavatta DJ, Yang J, Preston GA et al.: Epigenetic basis for aberrant upregulation of autoantigen genes in humans with ANCA vasculitis. J Clin Invest 2010; 120: 3209-3219.
Abdgawad M, Pettersson Å, Gunnarsson L et al.: Decreased Neutrophil Apoptosis in Quiescent ANCA Associated Systemic Vasculitis Systemic Vasculitis. PLoS One 2012; 7(3): e32439.
Jennette JC, Falk RJ: B cell-mediated pathogenesis of ANCA-mediated vasculitis. Semin Immunopathol 2014; 36: 327-338.
Chimenti MS, Ballanti E, Triggianese P et al.: Vasculitides and the Complement System: a Comprehensive Review. Clin Rev Allergy Immunol 2015; 49(3): 333-346.
Nakazawa D, Shida H, Tomaru U et al.: Enhanced Formation and Disordered Regulation of NETs in Myeloperoxidase-ANCA-Associated Microscopic Polyangiitis. J Am Soc Nephrol 2014; 25(5): 990-997.
Ohlsson SM, Ohlsson S, Söderberg D et al.: Neutrophils from vasculitis patients exhibit an increased propensity for activation by anti-neutrophil cytoplasmic antibodies. Clin Exp Immunol 2014; 176(3): 363-372.
Bosch X: LAMPs and NETs in the pathogenesis of ANCA vasculitis. J Am Soc Nephrol 2009; 20: 1654-1656.
Summers DM, Johnson RJ, Hudson A et al.: Effect of donor age and cold storage time on outcome in recipients of kidneys donated after circulatory death in the UK: a cohort study. Lancet 2013; 381: 727-734.
Morgan MD, Day CJ, Piper KP et al.: Patients with Wegener’s granulomatosis demonstrate a relative deficiency and functional impairment of T-regulatory cells. Immunology 2010; 130: 64-73.
Lepse N, Abdulahad WH, Rutgers A et al.: Altered B cell balance, but unaffected B cell capacity to limit monocyte activation in anti-neutrophil cytoplasmic antibody-associated vasculitis in remission. Rheumatology (Oxford) 2014; 53(9): 1683-1692.
Todd SK, Pepper RJ, Draibe J et al.: Regulatory B cells are numerically but not functionally deficient in anti-neutrophil cytoplasm antibody-associated vasculitis. Rheumatology (Oxford) 2014; 53(9): 1693-1703.
Ohlsson SM, Linge CP, Gullstrand B et al.: Serum from patients with systemic vasculitis induces alternatively activated macrophage M2c polarization. Clin Immunol 2014; 152(1-2): 10-19.
Tarzi RM, Liu J, Schneiter S et al.: CD14 expression is increased on monocytes in patients with ANCA-associated vasculitis and correlates with the expression of ANCA auto-antigens. Clin Exp Immunol 2015; 181(1): 65-75.
Bertram A, Lovric S, Engel A et al.: Circulating ADAM17 Level Reflects Disease Activity in Proteinase-3 ANCA-Associated Vasculitis. J Am Soc Nephrol 2015; 26(11): 2860-2870.
Lieberthal JG, Cuthbertson D, Carette S et al.: Urinary biomarkers in relapsing antineutrophil cytoplasmic antibody-associated vasculitis. J Rheumatol 2013; 40(5): 674-683.
Poulton CJ, Nachman PH, Hu Y et al.: Pathways to renal biopsy and diagnosis among patients with ANCA small-vessel vasculitis. Clin Exp Rheumatol 2013; 31(1S75): S32-37.
Noel N, Andrè C, Bengoufa D et al.: Performance evaluation of three assays for the detection of PR3-ANCA in granulomatosis with polyangiitis in daily practice. Autoimmun Rev 2013; 12(12): 1118-1122.
Knütter I, Hiemann R, Brumma T et al.: Automated interpretation of ANCA patterns – a new approach in the serology of ANCA-associated vasculitis. Arthritis Res Ther 2012; 14(6): R271.
de Joode AA, Roozendaal C, van der Leij MJ et al.: Performance of two strategies for urgent ANCA and anti-GBM analysis in vasculitis. Eur J Intern Med 2014; 25(2): 182-186.
Roth AJ, Ooi JD, Hess JJ et al.: Epitope specificity determines pathogenicity and detectability in ANCA-associated vasculitis. J Clin Invest 2013; 123(4): 1773-1783.
Minz RW, Chhabra S, Joshi K et al.: Renal histology in pauci-immune rapidly progressive glomerulonephritis: 8-year retrospective study. Indian J Pathol Microbiol 2012; 55(1): 28-32.
Sumida K, Ubara Y, Nomura K et al.: ANCA-associated crescentic glomerulonephritis with immune complex deposits. Clin Nephrol 2012; 77(6): 454-460.
de Joode AA, Sanders JS, Stegeman CA: Renal survival in proteinase 3 and myeloperoxidase ANCA-associated systemic vasculitis. Clin J Am Soc Nephrol 2013; 8(10): 1709-1717.
Thai LH, Charles P, Resche-Rigon M et al.: Are anti-proteinase-3 ANCA a useful marker of granulomatosis with polyangiitis (Wegener’s) relapses? Results of a retrospective study on 126 patients. Autoimmun Rev 2014; 13(3): 313-318.
Li ZY, Chang DY, Zhao MH, Chen M: Predictors of treatment resistance and relapse in antineutrophil cytoplasmic antibody-associated vasculitis: a study of 439 cases in a single Chinese center. Arthritis Rheumatol 2014; 66(7): 1920-1926.
Ford SL, Polkinghorne KR, Longano A et al.: Histopathologic and clinical predictors of kidney outcomes in ANCA-associated vasculitis. Kidney Dis 2014; 63(2): 227-235.
McAdoo SP, Tanna A, Randone O et al.: Necrotizing and crescentic glomerulonephritis presenting with preserved renal function in patients with underlying multisystem autoimmune disease: a retrospective case series. Rheumatology (Oxford) 2015; 54(6): 1025-1032.
Kristensen T, Gregersen JW, Krag SR, Ivarsen P: The relation between histopathological classification and renal outcome, ANCA subtype and treatment regimens in ANCA-associated vasculitis. Clin Exp Rheumatol 2016; 34(3S97): 105-110.
Jayne D, Rasmussen N, Andrassy K et al.: A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmicautoantibodies. N Engl J Med 2003; 349: 36-44.
Stone J H, Merkel PA, Spiera R et al.: Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 2010; 363: 221-232.
Guillevin L, Pagnoux C, Karras A et al.: Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med 2014; 371(19): 1771-1780.
Specks U, Merkel PA, Seo P et al.: Efficacy of Remission-Induction Regimens for ANCA-Associated Vasculitis. N Engl J Med 2013; 369(5): 417-427.
Smith RM, Jones RB, Guerry MJ et al.: Rituximab for remission maintenance in relapsing antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 2012; 64(11): 3760-3769.
Roberts DM, Jones RB, Smith RM et al.: Rituximab-associated hypogammaglobulinemia: incidence, predictors and outcomes in patients with multi-system autoimmune disease. J Autoimmun 2015; 57: 60-65.
Knight A, Sundström Y, Börjesson O et al.: Late-onset neutropenia after rituximab in ANCA-associated vasculitis. Scand J Rheumatol 2016; 7: 1-4.
Besada E, Koldingsnes W, Nossent JC: Long-term efficacy and safety of pre-emptive maintenance therapy with rituximab in granulomatosis with polyangiitis: results from a single centre. Rheumatology (Oxford) 2013; 52(11): 2041-2047.
Yates M, Watts RA, Bajema IM et al.: EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis 2016 Jun 23. DOI: 10.1136/annrheumdis-2016-209133.
otrzymano: 2016-08-04
zaakceptowano do druku: 2016-08-25

Adres do korespondencji:
*Maciej Szymczak
Department of Nephrology and Transplantation Medicine Wrocław Medical University
ul. Borowska 213, 50-556 Wrocław
mszymc@wp.pl

Postępy Nauk Medycznych 9/2016
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