Update on ANCA-associated vasculitis: from biomarkers to therapy

  • Martina Tedesco
  • Maurizio Gallieni
  • Francesca Pellegata
  • Mario Cozzolino
  • Federico AlbericiEmail author


ANCA-associated vasculitis (AAV) are the prototype of a disease characterised by the presence of a biomarker; ANCA positivity in fact is recorded in 90% of cases of GPA and MPA. The role of ANCA in the management of AAV ranges from diagnostic to prognostic purposes with also therapeutic implications. Changes in clinical practice with the increased use of rituximab have drawn attention to B-cells as a biomarker able to contribute to patient management. Cytokines and other circulating factors, although still at a research stage, may represent future biomarkers of interest or even therapeutic options. From the point of view of renal involvement in AAV, proteinuria and microhematuria are still the biomarkers employed in everyday clinical practice with a proposed role for emerging ones (MCP1, CD163 and CD25). The aim of this review is to discuss the role of well-known biomarkers in everyday clinical management of AAV patients as well as future perspectives for those that are still at a research stage with attention to therapeutic implications.


Vasculitis ANCA Biomarkers B-cells Rituximab 


Compliance with ethical standards

Conflict of interest

MT, MG, FP, MC and FA have nothing to disclose. The Authors declare no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.


  1. 1.
    Alberici F, Jayne DR (2014) Impact of rituximab trials on the treatment of ANCA-associated vasculitis. Nephrol Dial Transpl 29(6):1151–1159CrossRefGoogle Scholar
  2. 2.
    Lyons P, Peters J, Alberici F, Liley J, Coulson R, Astle W et al (2018) Genetically distinct clinical subsets, and associations with asthma and eosinophil abundance, within Eosinophilic Granulomatosis with Polyangiitis. bioRxiv.
  3. 3.
    Sinico RA, Di Toma L, Maggiore U, Bottero P, Radice A, Tosoni C et al (2005) Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in Churg-Strauss syndrome. Arthritis Rheum 52(9):2926–2935CrossRefPubMedGoogle Scholar
  4. 4.
    Martorana D, Bonatti F, Alberici F, Gioffredi A, Reina M, Urban ML et al (2016) Fcgamma-receptor 3B (FCGR3B) copy number variations in patients with eosinophilic granulomatosis with polyangiitis. J Allergy Clin Immunol 137(5):1597.e8–1599.e8CrossRefGoogle Scholar
  5. 5.
    Alberici F, Martorana D, Bonatti F, Gioffredi A, Lyons PA, Vaglio A (2014) Genetics of ANCA-associated vasculitides: HLA and beyond. Clin Exp Rheumatol 32(3 Suppl 82):S90–S97PubMedGoogle Scholar
  6. 6.
    Biomarkers Definitions Working G (2001) Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 69(3):89–95CrossRefGoogle Scholar
  7. 7.
    Davies DJ, Moran JE, Niall JF, Ryan GB (1982) Segmental necrotising glomerulonephritis with antineutrophil antibody: possible arbovirus aetiology? Br Med J (Clin Res Ed) 285(6342):606CrossRefGoogle Scholar
  8. 8.
    Sable-Fourtassou R, Cohen P, Mahr A, Pagnoux C, Mouthon L, Jayne D et al (2005) Antineutrophil cytoplasmic antibodies and the Churg-Strauss syndrome. Ann Intern Med 143(9):632–638CrossRefPubMedGoogle Scholar
  9. 9.
    Kettritz R (2012) How anti-neutrophil cytoplasmic autoantibodies activate neutrophils. Clin Exp Immunol 169(3):220–228CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Hong Y, Eleftheriou D, Hussain AA, Price-Kuehne FE, Savage CO, Jayne D et al (2012) Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles. J Am Soc Nephrol 23(1):49–62CrossRefPubMedGoogle Scholar
  11. 11.
    Little MA, Al-Ani B, Ren S, Al-Nuaimi H, Leite M Jr, Alpers CE et al (2012) Anti-proteinase 3 anti-neutrophil cytoplasm autoantibodies recapitulate systemic vasculitis in mice with a humanized immune system. PLoS One 7(1):e28626CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Watts R, Lane S, Hanslik T, Hauser T, Hellmich B, Koldingsnes W et al (2007) Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies. Ann Rheum Dis 66(2):222–227CrossRefPubMedGoogle Scholar
  13. 13.
    Damoiseaux J, Csernok E, Rasmussen N, Moosig F, van Paassen P, Baslund B et al (2017) Detection of antineutrophil cytoplasmic antibodies (ANCAs): a multicentre European Vasculitis Study Group (EUVAS) evaluation of the value of indirect immunofluorescence (IIF) versus antigen-specific immunoassays. Ann Rheum Dis 76(4):647–653CrossRefPubMedGoogle Scholar
  14. 14.
    Lionaki S, Blyth ER, Hogan SL, Hu Y, Senior BA, Jennette CE et al (2012) 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(10):3452–3462CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Tomasson G, Grayson PC, Mahr AD, Lavalley M, Merkel PA (2012) Value of ANCA measurements during remission to predict a relapse of ANCA-associated vasculitis–a meta-analysis. Rheumatology (Oxford) 51(1):100–109CrossRefGoogle Scholar
  16. 16.
    Kemna MJ, Damoiseaux J, Austen J, Winkens B, Peters J, van Paassen P et al (2015) ANCA as a predictor of relapse: useful in patients with renal involvement but not in patients with nonrenal disease. J Am Soc Nephrol 26(3):537–542CrossRefPubMedGoogle Scholar
  17. 17.
    Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS et al (2010) Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 363(3):221–232CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Fussner LA, Hummel AM, Schroeder DR, Silva F, Cartin-Ceba R, Snyder MR et al (2016) Factors determining the clinical utility of serial measurements of antineutrophil cytoplasmic antibodies targeting proteinase 3. Arthritis Rheumatol 68(7):1700–1710CrossRefPubMedGoogle Scholar
  19. 19.
    Jones RB, Tervaert JW, Hauser T, Luqmani R, Morgan MD, Peh CA et al (2010) Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 363(3):211–220CrossRefPubMedGoogle Scholar
  20. 20.
    Geetha D, Specks U, Stone JH, Merkel PA, Seo P, Spiera R et al (2015) Rituximab versus cyclophosphamide for ANCA-associated vasculitis with renal involvement. J Am Soc Nephrol 26(4):976–985CrossRefPubMedGoogle Scholar
  21. 21.
    Geetha D, Hruskova Z, Segelmark M, Hogan J, Morgan MD, Cavero T et al (2016) Rituximab for treatment of severe renal disease in ANCA associated vasculitis. J Nephrol 29(2):195–201CrossRefPubMedGoogle Scholar
  22. 22.
    Guillevin L, Pagnoux C, Karras A, Khouatra C, Aumaitre O, Cohen P et al (2014) Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med 371(19):1771–1780CrossRefPubMedGoogle Scholar
  23. 23.
    Alberici F, Smith RM, Jones RB, Roberts DM, Willcocks LC, Chaudhry A et al (2015) Long-term follow-up of patients who received repeat-dose rituximab as maintenance therapy for ANCA-associated vasculitis. Rheumatology (Oxford) 54(7):1153–1160CrossRefGoogle Scholar
  24. 24.
    Gopaluni S, Smith RM, Lewin M, McAlear CA, Mynard K, Jones RB et al (2017) Rituximab versus azathioprine as therapy for maintenance of remission for anti-neutrophil cytoplasm antibody-associated vasculitis (RITAZAREM): study protocol for a randomized controlled trial. Trials 18(1):112CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Terrier B, Pagnoux C, Perrodeau E, Karras A, Khouatra C, Aumaitre O et al (2018) Long-term efficacy of remission-maintenance regimens for ANCA-associated vasculitides. Ann Rheum Dis 77(8):1150–1156CrossRefPubMedGoogle Scholar
  26. 26.
    Charles P, Terrier B, Perrodeau E, Cohen P, Faguer S, Huart A et al (2018) 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(8):1143–1149PubMedGoogle Scholar
  27. 27.
    Unizony S, Villarreal M, Miloslavsky EM, Lu N, Merkel PA, Spiera R et al (2016) Clinical outcomes of treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis based on ANCA type. Ann Rheum Dis 75(6):1166–1169CrossRefPubMedGoogle Scholar
  28. 28.
    Karras A, Pagnoux C, Haubitz M, Groot K, Puechal X, Tervaert JWC et al (2017) Randomised controlled trial of prolonged treatment in the remission phase of ANCA-associated vasculitis. Ann Rheum Dis 76(10):1662–1668CrossRefPubMedGoogle Scholar
  29. 29.
    de Joode AAE, Sanders JSF, Puechal X, Guillevin LP, Hiemstra TF, Flossmann O et al (2017) Long term azathioprine maintenance therapy in ANCA-associated vasculitis: combined results of long-term follow-up data. Rheumatology (Oxford) 56(11):1894–1901CrossRefGoogle Scholar
  30. 30.
    Jayne DR, Gaskin G, Rasmussen N, Abramowicz D, Ferrario F, Guillevin L et al (2007) Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol 18(7):2180–2188CrossRefPubMedGoogle Scholar
  31. 31.
    Walsh M, Catapano F, Szpirt W, Thorlund K, Bruchfeld A, Guillevin L et al (2011) Plasma exchange for renal vasculitis and idiopathic rapidly progressive glomerulonephritis: a meta-analysis. Am J Kidney Dis 57(4):566–574CrossRefPubMedGoogle Scholar
  32. 32.
    Walsh M, Merkel PA, Peh CA, Szpirt W, Guillevin L, Pusey CD et al (2013) Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS): protocol for a randomized controlled trial. Trials 14:73CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Lorant T, Bengtsson M, Eich T, Eriksson BM, Winstedt L, Jarnum S et al (2018) Safety, immunogenicity, pharmacokinetics, and efficacy of degradation of anti-HLA antibodies by IdeS (imlifidase) in chronic kidney disease patients. Am J Transpl 18(11):2752–2762CrossRefGoogle Scholar
  34. 34.
    Cassia M, Alberici F, Gallieni M, Jayne D (2017) Lupus nephritis and B-cell targeting therapy. Expert Rev Clin Immunol 13(10):951–962CrossRefPubMedGoogle Scholar
  35. 35.
    Jones RB, Furuta S, Tervaert JW, Hauser T, Luqmani R, Morgan MD et al (2015) Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis: 2-year results of a randomised trial. Ann Rheum Dis 74(6):1178–1182CrossRefPubMedGoogle Scholar
  36. 36.
    Ferraro AJ, Smith SW, Neil D, Savage CO (2008) Relapsed Wegener’s granulomatosis after rituximab therapy–B cells are present in new pathological lesions despite persistent ‘depletion’ of peripheral blood. Nephrol Dial Transpl 23(9):3030–3032CrossRefGoogle Scholar
  37. 37.
    Alberici F, Smith RM, Cassia M, Colombo F, Brenna I, Jones RB et al (2016) Clinical predictors of response to rituximab in ANCA-associated vasculitis: a European cohort [Abstract]. Nephrol Dial Transpl 31(Supplement 1):i77–i78CrossRefGoogle Scholar
  38. 38.
    Van Parijs L, Abbas AK (1998) Homeostasis and self-tolerance in the immune system: turning lymphocytes off. Science 280(5361):243–248CrossRefPubMedGoogle Scholar
  39. 39.
    Todd SK, Pepper RJ, Draibe J, Tanna A, Pusey CD, Mauri C et al (2014) Regulatory B cells are numerically but not functionally deficient in anti-neutrophil cytoplasm antibody-associated vasculitis. Rheumatology (Oxford) 53(9):1693–1703CrossRefGoogle Scholar
  40. 40.
    Bunch DO, McGregor JG, Khandoobhai NB, Aybar LT, Burkart ME, Hu Y et al (2013) Decreased CD5(+) B cells in active ANCA vasculitis and relapse after rituximab. Clin J Am Soc Nephrol 8(3):382–391CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Unizony S, Lim N, Phippard DJ, Carey VJ, Miloslavsky EM, Tchao NK et al (2015) Peripheral CD5+ B cells in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol 67(2):535–544CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Bunch DO, Mendoza CE, Aybar LT, Kotzen ES, Colby KR, Hu Y et al (2015) Gleaning relapse risk from B cell phenotype: decreased CD5+ B cells portend a shorter time to relapse after B cell depletion in patients with ANCA-associated vasculitis. Ann Rheum Dis 74(9):1784–1786CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Iwata Y, Matsushita T, Horikawa M, Dilillo DJ, Yanaba K, Venturi GM et al (2011) Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells. Blood 117(2):530–541CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Blair PA, Norena LY, Flores-Borja F, Rawlings DJ, Isenberg DA, Ehrenstein MR et al (2010) CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients. Immunity 32(1):129–140CrossRefPubMedGoogle Scholar
  45. 45.
    Wilde B, Thewissen M, Damoiseaux J, Knippenberg S, Hilhorst M, van Paassen P et al (2013) Regulatory B cells in ANCA-associated vasculitis. Ann Rheum Dis 72(8):1416–1419CrossRefPubMedGoogle Scholar
  46. 46.
    Lepse N, Abdulahad WH, Rutgers A, Kallenberg CG, Stegeman CA, Heeringa P (2014) Altered B cell balance, but unaffected B cell capacity to limit monocyte activation in anti-neutrophil cytoplasmic antibody-associated vasculitis in remission. Rheumatology (Oxford) 53(9):1683–1692CrossRefGoogle Scholar
  47. 47.
    Md Yusof MY, Vital EM, Das S, Dass S, Arumugakani G, Savic S et al (2015) Repeat cycles of rituximab on clinical relapse in ANCA-associated vasculitis: identifying B cell biomarkers for relapse to guide retreatment decisions. Ann Rheum Dis 74(9):1734–1738CrossRefPubMedGoogle Scholar
  48. 48.
    Thiel J, Rizzi M, Engesser M, Dufner AK, Troilo A, Lorenzetti R et al (2017) B cell repopulation kinetics after rituximab treatment in ANCA-associated vasculitides compared to rheumatoid arthritis, and connective tissue diseases: a longitudinal observational study on 120 patients. Arthritis Res Ther 19(1):101CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    McKinney EF, Lyons PA, Carr EJ, Hollis JL, Jayne DR, Willcocks LC et al (2010) A CD8 + T cell transcription signature predicts prognosis in autoimmune disease. Nat Med 16(5):586–591 (1p following 91) CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Neel A, Bucchia M, Neel M, Tilly G, Caristan A, Yap M, et al. Dampening of CD8+ T cell response by b cell depletion therapy in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis RheumatolGoogle Scholar
  51. 51.
    McClure M, Gopaluni S, Jayne D, Jones R (2018) B cell therapy in ANCA-associated vasculitis: current and emerging treatment options. Nat Rev Rheumatol 14(10):580–591CrossRefPubMedGoogle Scholar
  52. 52.
    Schneeweis C, Rafalowicz M, Feist E, Buttgereit F, Rudolph PE, Burmester GR et al (2010) Increased levels of BLyS and sVCAM-1 in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitides (AAV). Clin Exp Rheumatol 28(1 Suppl 57):62–66PubMedGoogle Scholar
  53. 53.
    Liu Z, Davidson A (2011) BAFF and selection of autoreactive B cells. Trends Immunol 32(8):388–394CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Jayne D, Blockmans D, Luqmani R, Moiseev S, Ji B, Green Y et al (2019) Efficacy and safety of belimumab and azathioprine for maintenance of remission in ANCA-associated vasculitis: a randomized controlled study. Arthritis Rheumatol 71(6):952–963CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Thien M, Phan TG, Gardam S, Amesbury M, Basten A, Mackay F et al (2004) Excess BAFF rescues self-reactive B cells from peripheral deletion and allows them to enter forbidden follicular and marginal zone niches. Immunity 20(6):785–798CrossRefPubMedGoogle Scholar
  56. 56.
    Alberici F, Smith RM, Fonseca M, Willcocks LC, Jones RB, Holle JU et al (2017) Association of a TNFSF13B (BAFF) regulatory region single nucleotide polymorphism with response to rituximab in antineutrophil cytoplasmic antibody-associated vasculitis. J Allergy Clin Immunol 139(5):1684.e10–1687.e10CrossRefGoogle Scholar
  57. 57.
    Schreiber A, Xiao H, Jennette JC, Schneider W, Luft FC, Kettritz R (2009) C5a receptor mediates neutrophil activation and ANCA-induced glomerulonephritis. J Am Soc Nephrol 20(2):289–298CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Gou SJ, Yuan J, Chen M, Yu F, Zhao MH (2013) Circulating complement activation in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Kidney Int 83(1):129–137CrossRefPubMedGoogle Scholar
  59. 59.
    Augusto JF, Langs V, Demiselle J, Lavigne C, Brilland B, Duveau A et al (2016) Low serum complement C3 levels at diagnosis of renal ANCA-associated vasculitis is associated with poor prognosis. PLoS One 11(7):e0158871CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Crnogorac M, Horvatic I, Kacinari P, Ljubanovic DG, Galesic K (2018) Serum C3 complement levels in ANCA associated vasculitis at diagnosis is a predictor of patient and renal outcome. J Nephrol 31(2):257–262CrossRefPubMedGoogle Scholar
  61. 61.
    Hilhorst M, van Paassen P, van Rie H, Bijnens N, Heerings-Rewinkel P, van Breda Vriesman P et al (2017) Complement in ANCA-associated glomerulonephritis. Nephrol Dial Transpl 32(8):1302–1313CrossRefGoogle Scholar
  62. 62.
    Manenti L, Vaglio A, Gnappi E, Maggiore U, Allegri L, Allinovi M et al (2015) 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(12):2143–2151CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Xiao H, Schreiber A, Heeringa P, Falk RJ, Jennette JC (2007) Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies. Am J Pathol 170(1):52–64CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Jayne DRW, Bruchfeld AN, Harper L, Schaier M, Venning MC, Hamilton P et al (2017) Randomized trial of C5a receptor inhibitor avacopan in ANCA-associated vasculitis. J Am Soc Nephrol 28(9):2756–2767CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Manenti L, Urban ML, Maritati F, Galetti M, Vaglio A (2017) Complement blockade in ANCA-associated vasculitis: an index case, current concepts and future perspectives. Intern Emerg Med 12(6):727–731CrossRefPubMedGoogle Scholar
  66. 66.
    Monach PA, Warner RL, Tomasson G, Specks U, Stone JH, Ding L et al (2013) Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis. Ann Rheum Dis 72(8):1342–1350CrossRefPubMedGoogle Scholar
  67. 67.
    Berti A, Warner R, Johnson K, Cornec D, Schroeder D, Kabat B et al (2018) Brief report: circulating cytokine profiles and antineutrophil cytoplasmic antibody specificity in patients with antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol 70(7):1114–1121CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Berti A, Cavalli G, Campochiaro C, Guglielmi B, Baldissera E, Cappio S et al (2015) Interleukin-6 in ANCA-associated vasculitis: rationale for successful treatment with tocilizumab. Semin Arthritis Rheum 45(1):48–54CrossRefPubMedGoogle Scholar
  69. 69.
    Sakai R, Kondo T, Kurasawa T, Nishi E, Okuyama A, Chino K et al (2017) Current clinical evidence of tocilizumab for the treatment of ANCA-associated vasculitis: a prospective case series for microscopic polyangiitis in a combination with corticosteroids and literature review. Clin Rheumatol 36(10):2383–2392CrossRefPubMedGoogle Scholar
  70. 70.
    Walsh M, Casian A, Flossmann O, Westman K, Hoglund P, Pusey C et al (2013) Long-term follow-up of patients with severe ANCA-associated vasculitis comparing plasma exchange to intravenous methylprednisolone treatment is unclear. Kidney Int 84(2):397–402CrossRefPubMedGoogle Scholar
  71. 71.
    Rhee RL, Davis JC, Ding L, Fervenza FC, Hoffman GS, Kallenberg CGM et al (2018) The utility of urinalysis in determining the risk of renal relapse in ANCA-associated vasculitis. Clin J Am Soc Nephrol 13(2):251–257CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Lv L, Chang DY, Li ZY, Chen M, Hu Z, Zhao MH (2017) Persistent hematuria in patients with antineutrophil cytoplasmic antibody-associated vasculitis during clinical remission: chronic glomerular lesion or low-grade active renal vasculitis? BMC Nephrol 18(1):354CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Magrey MN, Villa-Forte A, Koening CL, Myles JL, Hoffman GS (2009) Persistent hematuria after induction of remission in Wegener granulomatosis: a therapeutic dilemma. Medicine (Baltimore) 88(6):315–321CrossRefGoogle Scholar
  74. 74.
    Oomatia A, Moran SM, Kennedy C, Sequeira R, Hamour S, Burns A et al (2016) Prolonged duration of renal recovery following ANCA-associated glomerulonephritis. Am J Nephrol 43(2):112–119CrossRefPubMedGoogle Scholar
  75. 75.
    Geetha D, Seo P, Ellis C, Kuperman M, Levine SM (2012) Persistent or new onset microscopic hematuria in patients with small vessel vasculitis in remission: findings on renal biopsy. J Rheumatol 39(7):1413–1417CrossRefPubMedGoogle Scholar
  76. 76.
    Boring L, Gosling J, Chensue SW, Kunkel SL, Farese RV Jr, Broxmeyer HE et al (1997) Impaired monocyte migration and reduced type 1 (Th1) cytokine responses in C-C chemokine receptor 2 knockout mice. J Clin Invest 100(10):2552–2561CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Jonsson N, Erlandsson E, Gunnarsson L, Pettersson A, Ohlsson S (2018) Monocyte chemoattractant protein-1 in antineutrophil cytoplasmic autoantibody-associated vasculitis: biomarker potential and association with polymorphisms in the MCP-1 and the cc chemokine receptor-2 gene. Mediat Inflamm 2018:6861257CrossRefGoogle Scholar
  78. 78.
    Rovin BH, Rumancik M, Tan L, Dickerson J (1994) Glomerular expression of monocyte chemoattractant protein-1 in experimental and human glomerulonephritis. Lab Invest 71(4):536–542PubMedGoogle Scholar
  79. 79.
    Wada T, Furuichi K, Sakai N, Iwata Y, Yoshimoto K, Shimizu M et al (2000) Up-regulation of monocyte chemoattractant protein-1 in tubulointerstitial lesions of human diabetic nephropathy. Kidney Int 58(4):1492–1499CrossRefPubMedGoogle Scholar
  80. 80.
    Tam FW, Sanders JS, George A, Hammad T, Miller C, Dougan T et al (2004) Urinary monocyte chemoattractant protein-1 (MCP-1) is a marker of active renal vasculitis. Nephrol Dial Transpl 19(11):2761–2768CrossRefGoogle Scholar
  81. 81.
    O’Reilly VP, Wong L, Kennedy C, Elliot LA, O’Meachair S, Coughlan AM et al (2016) Urinary soluble CD163 in active renal vasculitis. J Am Soc Nephrol 27(9):2906–2916CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Daly A, Walsh C, Feighery C, O’Shea U, Jackson J, Whelan A (2006) Serum levels of soluble CD163 correlate with the inflammatory process in coeliac disease. Aliment Pharmacol Ther 24(3):553–559CrossRefPubMedGoogle Scholar
  83. 83.
    Zhao L, David MZ, Hyjek E, Chang A, Meehan SM (2015) M2 macrophage infiltrates in the early stages of ANCA-associated pauci-immune necrotizing GN. Clin J Am Soc Nephrol 10(1):54–62CrossRefPubMedGoogle Scholar
  84. 84.
    Endo N, Tsuboi N, Furuhashi K, Shi Y, Du Q, Abe T et al (2016) Urinary soluble CD163 level reflects glomerular inflammation in human lupus nephritis. Nephrol Dial Transpl 31(12):2023–2033CrossRefGoogle Scholar
  85. 85.
    Abdulahad WH, Kallenberg CG, Limburg PC, Stegeman CA (2009) Urinary CD4+ effector memory T cells reflect renal disease activity in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 60(9):2830–2838CrossRefPubMedGoogle Scholar
  86. 86.
    Dekkema GJ, Abdulahad WH, Bijma T, Moran SM, Ryan L, Little MA et al (2019) Urinary and serum soluble CD25 complements urinary soluble CD163 to detect active renal anti-neutrophil cytoplasmic autoantibody-associated vasculitis: a cohort study. Nephrol Dial Transpl 34(2):234–242CrossRefGoogle Scholar
  87. 87.
    Moran SM, Monach PA, Zgaga L, Cuthbertson D, Carette S, Khalidi NA et al (2018) Urinary soluble CD163 and monocyte chemoattractant protein-1 in the identification of subtle renal flare in anti-neutrophil cytoplasmic antibody-associated vasculitis. Nephrol Dial Transpl. CrossRefGoogle Scholar
  88. 88.
    Kain R, Tadema H, McKinney EF, Benharkou A, Brandes R, Peschel A et al (2012) High prevalence of autoantibodies to hLAMP-2 in anti-neutrophil cytoplasmic antibody-associated vasculitis. J Am Soc Nephrol 23(3):556–566CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Roth AJ, Brown MC, Smith RN, Badhwar AK, Parente O, Chung H et al (2012) Anti-LAMP-2 antibodies are not prevalent in patients with antineutrophil cytoplasmic autoantibody glomerulonephritis. J Am Soc Nephrol 23(3):545–555CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Peschel A, Basu N, Benharkou A, Brandes R, Brown M, Dieckmann R et al (2014) Autoantibodies to hLAMP-2 in ANCA-negative pauci-immune focal necrotizing GN. J Am Soc Nephrol 25(3):455–463CrossRefPubMedGoogle Scholar
  91. 91.
    Berden AE, Nolan SL, Morris HL, Bertina RM, Erasmus DD, Hagen EC et al (2010) Anti-plasminogen antibodies compromise fibrinolysis and associate with renal histology in ANCA-associated vasculitis. J Am Soc Nephrol 21(12):2169–2179CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Goceroglu A, Grenmyr E, Berden AE, Hagen EC, Bunch D, Sommarin Y et al (2018) Anti-plasminogen antibodies in ANCA-associated vasculitis: an optimized anti-plasminogen assay. PLoS One 13(11):e0207064CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Suzuki K, Nagao T, Itabashi M, Hamano Y, Sugamata R, Yamazaki Y et al (2014) A novel autoantibody against moesin in the serum of patients with MPO-ANCA-associated vasculitis. Nephrol Dial Transpl 29(6):1168–1177CrossRefGoogle Scholar
  94. 94.
    Soderberg D, Kurz T, Motamedi A, Hellmark T, Eriksson P, Segelmark M (2015) Increased levels of neutrophil extracellular trap remnants in the circulation of patients with small vessel vasculitis, but an inverse correlation to anti-neutrophil cytoplasmic antibodies during remission. Rheumatology (Oxford) 54(11):2085–2094CrossRefGoogle Scholar
  95. 95.
    Nasrallah M, Pouliot Y, Hartmann B, Dunn P, Thomson E, Wiser J et al (2015) Reanalysis of the Rituximab in ANCA-Associated Vasculitis trial identifies granulocyte subsets as a novel early marker of successful treatment. Arthritis Res Ther 17:262CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Bottazzi B, Garlanda C, Cotena A, Moalli F, Jaillon S, Deban L et al (2009) The long pentraxin PTX3 as a prototypic humoral pattern recognition receptor: interplay with cellular innate immunity. Immunol Rev 227(1):9–18CrossRefPubMedGoogle Scholar
  97. 97.
    Fazzini F, Peri G, Doni A, Dell’Antonio G, Dal Cin E, Bozzolo E et al (2001) PTX3 in small-vessel vasculitides: an independent indicator of disease activity produced at sites of inflammation. Arthritis Rheum 44(12):2841–2850CrossRefPubMedGoogle Scholar
  98. 98.
    Simon A, Subra JF, Guilpain P, Jeannin P, Pignon P, Blanchard S et al (2016) Detection of anti-pentraxin-3 autoantibodies in ANCA-associated vasculitis. PLoS One 11(1):e0147091CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Augusto JF, Onno C, Blanchard S, Dubuquoi S, Mantovani A, Chevailler A et al (2009) Detection of anti-PTX3 autoantibodies in systemic lupus erythematosus. Rheumatology (Oxford) 48(4):442–444CrossRefGoogle Scholar
  100. 100.
    Nishide M, Nojima S, Ito D, Takamatsu H, Koyama S, Kang S et al (2017) Semaphorin 4D inhibits neutrophil activation and is involved in the pathogenesis of neutrophil-mediated autoimmune vasculitis. Ann Rheum Dis 76(8):1440–1448CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    LaGanke C, Samkoff L, Edwards K, Jung Henson L, Repovic P, Lynch S et al (2017) Safety/tolerability of the anti-semaphorin 4D Antibody VX15/2503 in a randomized phase 1 trial. Neurol Neuroimmunol Neuroinflamm 4(4):e367CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Woywodt A, Streiber F, de Groot K, Regelsberger H, Haller H, Haubitz M (2003) Circulating endothelial cells as markers for ANCA-associated small-vessel vasculitis. Lancet 361(9353):206–210CrossRefPubMedGoogle Scholar
  103. 103.
    Erdbruegger U, Grossheim M, Hertel B, Wyss K, Kirsch T, Woywodt A et al (2008) Diagnostic role of endothelial microparticles in vasculitis. Rheumatology (Oxford) 47(12):1820–1825CrossRefGoogle Scholar

Copyright information

© Italian Society of Nephrology 2019

Authors and Affiliations

  1. 1.Nephrology Unit and Immunology ClinicASST Santi Paolo e CarloMilanItaly
  2. 2.ASST Fatebenefratelli SaccoMilanItaly
  3. 3.Dipartimento di Scienze Biomediche e Cliniche “L. Sacco”University of MilanoMilanItaly
  4. 4.Dipartimento di Scienze della SaluteUniversity of MilanoMilanItaly

Personalised recommendations