Skip to main content

Advertisement

Log in

Serum ANCA as Disease Biomarkers: Clinical Implications Beyond Vasculitis

  • Published:
Clinical Reviews in Allergy & Immunology Aims and scope Submit manuscript

Abstract

Usually associated with autoimmune diseases, anti-neutrophil cytoplasmic antibodies are also detected in other conditions, such as infections, malignancies, and after intake of certain drugs. Even if the mechanisms of production and their pathogenic role have not been fully elucidated yet, ANCA are widely recognized as a clinically alarming finding due to their association with various disorders. While ANCA target several autoantigens, proteinase-3, and myeloperoxidase are the ones proved to be most frequently related to chronic inflammation and tissue damage in murine models. Albeit these autoantibodies could be present as an isolated observation without any implications, ANCA are frequently used in clinical practice to guide the diagnosis in a suspect of small vessel vasculitis. Conditions that should prompt the clinician to test ANCA status range from various forms of lung disease to renal or peripheral nervous system impairment. ANCA positivity in the presence of an autoimmune disease, especially rheumatoid arthritis, or connective tissue diseases, is frequently correlated with more clinical complications and treatment inefficacy, even in the absence of signs of vasculitis. For this reason, it has been postulated that ANCA could represent the final expression of an immune dysregulation rather than a pathogenic event responsible for organs damage. Recently, it has also been proposed that ANCA specificity (PR3 or MPO) could possibly define ANCA-associated vasculitides better than clinical phenotype. This review aims at summarizing the latest advancements in the field of ANCA study and clinical interpretation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Ramponi G, Folci M, De Santis M et al (2021) The biology, pathogenetic role, clinical implications, and open issues of serum anti-neutrophil cytoplasmic antibodies. Autoimmun Rev 20

  2. Radice A, Sinico RA (2005) Antineutrophil cytoplasmic antibodies (ANCA). Autoimmunity 38:93–103. https://doi.org/10.1080/08916930400022673

    Article  CAS  Google Scholar 

  3. Moiseev S, Cohen Tervaert JW, Arimura Y, Bogdanos DP, Csernok E, Damoiseaux J, Ferrante M, Flores-Suárez LF, Fritzler MJ, Invernizzi P, Jayne D, Jennette JC, Little MA, McAdoo SP, Novikov P, Pusey CD, Radice A, Salama AD, Savige JA, Segelmark M, Shoenfeld Y, Sinico RA, Sousa MJ, Specks U, Terrier B, Tzioufas AG, Vermeire S, Zhao MH, Bossuyt X (2020) International consensus on ANCA testing beyond systemic vasculitis. Autoimmun Rev 19(9):102618. https://doi.org/10.1016/j.autrev.2020.102618. Epub 2020 Jul 12. PMID: 32663621

  4. van Beers JJBC, Vanderlocht J, Roozendaal C, Damoiseaux J (2019) Detection of anti-neutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence. Methods Mol Biol 1901:47–62. https://doi.org/10.1007/978-1-4939-8949-2_4

    Article  CAS  Google Scholar 

  5. Suwanchote S, Rachayon M, Rodsaward P et al (2018) Anti-neutrophil cytoplasmic antibodies and their clinical significance. Clin Rheumatol 37:875–884

    Article  Google Scholar 

  6. Bossuyt X, Cohen Tervaert JW, Arimura Y et al (2017) Revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis. Nat Rev Rheumatol 13:683–692. https://doi.org/10.1038/nrrheum.2017.140

    Article  Google Scholar 

  7. Damoiseaux J, Csernok E, Rasmussen N 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 76:647–653. https://doi.org/10.1136/annrheumdis-2016-209507

    Article  CAS  Google Scholar 

  8. Csernok E, Damoiseaux J, Rasmussen N et al (2016) Evaluation of automated multi-parametric indirect immunofluorescence assays to detect anti-neutrophil cytoplasmic antibodies (ANCA) in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Autoimmun Rev 15:736–741. https://doi.org/10.1016/J.AUTREV.2016.03.010

    Article  CAS  Google Scholar 

  9. Moiseev S, Bossuyt X, Arimura Y et al (2020) International Consensus on ANCA Testing in Eosinophilic Granulomatosis with Polyangiitis. Am J Respir Crit Care Med. https://doi.org/10.1164/rccm.202005-1628so

    Article  Google Scholar 

  10. Pendergraft WF, Preston GA, Shah RR et al (2004) Autoimmunity is triggered by cPR-3(105–201), a protein complementary to human autoantigen proteinase-3. Nat Med 10:72–79. https://doi.org/10.1038/nm968

    Article  CAS  Google Scholar 

  11. Stegeman CA, Tervaert JW, Sluiter WJ et al (1994) Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis. Ann Intern Med 120:12–7

    Article  CAS  Google Scholar 

  12. Pudifin DJ, Duursma J, Gathiram V, Jackson TF (1994) Invasive amoebiasis is associated with the development of anti-neutrophil cytoplasmic antibody. Clin Exp Immunol 97:48–51

    Article  CAS  Google Scholar 

  13. Gilligan HM, Bredy B, Brady HR et al (1996) Antineutrophil cytoplasmic autoantibodies interact with primary granule constituents on the surface of apoptotic neutrophils in the absence of neutrophil priming. J Exp Med 184:2231–41

    Article  CAS  Google Scholar 

  14. Brinkmann V, Reichard U, Goosmann C et al (2004) Neutrophil extracellular traps kill bacteria. Science (80-) 303:1532–1535

  15. Sangaletti S, Tripodo C, Chiodoni C et al (2012) Neutrophil extracellular traps mediate transfer of cytoplasmic neutrophil antigens to myeloid dendritic cells toward ANCA induction and associated autoimmunity. Blood 120:3007–3018

    Article  CAS  Google Scholar 

  16. Kessenbrock K, Krumbholz M, Schönermarck U et al (2009) Netting neutrophils in autoimmune small-vessel vasculitis. Nat Med 15:623–5

    Article  CAS  Google Scholar 

  17. Frangou E, Vassilopoulos D, Boletis J, Boumpas DT (2019) An emerging role of neutrophils and NETosis in chronic inflammation and fibrosis in systemic lupus erythematosus (SLE) and ANCA-associated vasculitides (AAV): Implications for the pathogenesis and treatment. Autoimmun Rev 18:751–760

    Article  CAS  Google Scholar 

  18. Valenzuela LM, Draibe JB, Oliveras XF, Matamoros OB, Garrit JM, Ambrós JT (2019) T-lymphocyte in ANCA-associated vasculitis: what do we know? A pathophysiological and therapeutic approach. Clin Kidney J 12(4):503–511. https://doi.org/10.1093/ckj/sfz029

  19. Sanders JS, Huitma MG, Kallenberg CG, Stegeman CA (2006) Plasma levels of soluble interleukin 2 receptor, soluble CD30, interleukin 10 and B cell activator of the tumour necrosis factor family during follow-up in vasculitis associated with proteinase 3-antineutrophil cytoplasmic antibodies: associations with disease activity and relapse. Ann Rheum Dis 65(11):1484–1489. https://doi.org/10.1136/ard.2005.046219. Epub 2006 Feb 27. PMID: 16504995; PMCID: PMC1798350

  20. Marinaki S, Neumann I, Kalsch A-I et al (2005) Abnormalities of CD4+ T cell subpopulations in ANCA-associated vasculitis. Clin Exp Immunol 140:181–191. https://doi.org/10.1111/j.1365-2249.2005.02731.x

    Article  CAS  Google Scholar 

  21. Abdulahad WH, Stegeman CA, Kallenberg CG (2009) Review article: The role of CD4(+) T cells in ANC Aassociated systemic vasculitis. Nephrology (Carlton) 14(1):26–32. https://doi.org/10.1111/j.1440-1797.2008.01069.x. Epub 2009 Jan 8. PMID: 19143940

  22. Yoshida M, Iwahori T, Nakabayashi I, Akashi M, Watanabe T, Yoshikawa N (2005) In vitro production of myeloperoxidase anti-neutrophil cytoplasmic antibody and establishment of Th1-type T cell lines from peripheral blood lymphocytes of patients. Clin Exp Rheumatol 23(2):227–230. PMID: 15895894

  23. Abdulahad WH, Lepse N, Stegeman CA, Huitema MG, Doornbos-van der Meer B, Tadema H, Rutgers A, Limburg PC, Kallenberg CG, Heeringa P (2013) Increased frequency of circulating IL-21 producing Th-cells in patients with granulomatosis with polyangiitis (GPA). Arthritis Res Ther 15(3):R70. https://doi.org/10.1186/ar4247. PMID: 23799890; PMCID: PMC4060544

  24. Ruth AJ, Kitching AR, Kwan RY, Odobasic D, Ooi JD, Timoshanko JR, Hickey MJ, Holdsworth SR (2006) Anti-neutrophil cytoplasmic antibodies and effector CD4+ cells play nonredundant roles in anti-myeloperoxidase crescentic glomerulonephritis. J Am Soc Nephrol 17(7):1940–1949. https://doi.org/10.1681/ASN.2006020108. Epub 2006 Jun 12. PMID: 16769746

  25. Hagen EC, de Keizer RJ, Andrassy K, van Boven WP, Bruijn JA, van Es LA, van der Woude FJ (1995) Compassionate treatment of Wegener's granulomatosis with rabbit anti-thymocyte globulin. Clin Nephrol 43(6):351–359. PMID: 7554518

  26. Xiao H, Schreiber A, Heeringa P et al (2007) Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies. Am J Pathol 170:52–64

    Article  CAS  Google Scholar 

  27. Gómez-Puerta JA, Bosch X (2009) Anti-neutrophil cytoplasmic antibody pathogenesis in small-vessel vasculitis: an update. Am J Pathol 175:1790–1798. https://doi.org/10.2353/ajpath.2009.090533

    Article  CAS  Google Scholar 

  28. Berglin E, Mohammad AJ, Dahlqvist J et al (2021) Anti-neutrophil cytoplasmic antibodies predate symptom onset of ANCA-associated vasculitis A case-control study. J Autoimmun 117. https://doi.org/10.1016/j.jaut.2020.102579

  29. Jennette JC (2013) Overview of the 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Clin Exp Nephrol 17:603–606. https://doi.org/10.1007/s10157-013-0869-6

    Article  Google Scholar 

  30. Robson JC, Grayson PC, Ponte C et al (2018) OP0021 Draft classification criteria for the ANCA associated vasculitides. In: Wednesday, 13 June 2018. BMJ Publishing Group Ltd and European League Against Rheumatism 60.2–61

  31. Robson J, Grayson P, Ponte C et al (2019) Classification criteria for the ANCA-associated vasculitides. Rheumatology 58. https://doi.org/10.1093/rheumatology/kez058.050

  32. Seeliger B, Sznajd J, Robson JC et al (2017) Are the 1990 American College of Rheumatology vasculitis classification criteria still valid? Rheumatology 56:1154–1161. https://doi.org/10.1093/rheumatology/kex075

    Article  CAS  Google Scholar 

  33. Comarmond C, Cacoub P (2014) Granulomatosis with polyangiitis (Wegener): clinical aspects and treatment. Autoimmun Rev 13:1121–1125. https://doi.org/10.1016/j.autrev.2014.08.017

    Article  Google Scholar 

  34. Trimarchi M, Sinico RA, Teggi R et al (2013) Otorhinolaryngological manifestations in granulomatosis with polyangiitis (Wegener’s). Autoimmun Rev 12:501–505. https://doi.org/10.1016/j.autrev.2012.08.010

    Article  Google Scholar 

  35. Hoffman GS, Kerr GS, Leavitt RY et al (1992) Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med 116:488–98

    Article  CAS  Google Scholar 

  36. Girard C, Charles P, Terrier B et al (2015) Tracheobronchial stenoses in granulomatosis with polyangiitis (Wegenerʼs). Medicine (Baltimore) 94:e1088. https://doi.org/10.1097/MD.0000000000001088

    Article  CAS  Google Scholar 

  37. Little MA, Nightingale P, Verburgh CA et al (2010) Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis. Ann Rheum Dis 69:1036–1043. https://doi.org/10.1136/ard.2009.109389

    Article  Google Scholar 

  38. Chang D, Wu L, Liu G et al (2012) Re-evaluation of the histopathologic classification of ANCA-associated glomerulonephritis: a study of 121 patients in a single center. Nephrol Dial Transplant 27:2343–2349. https://doi.org/10.1093/ndt/gfr643

    Article  Google Scholar 

  39. Dufour J-F, Le Gallou T, Cordier J-F et al (2012) Urogenital manifestations in Wegener granulomatosis: a study of 11 cases and review of the literature. Medicine (Baltimore) 91:67–74. https://doi.org/10.1097/MD.0b013e318239add6

    Article  Google Scholar 

  40. Seror R, Mahr A, Ramanoelina J et al (2006) Central nervous system involvement in Wegener granulomatosis. Medicine (Baltimore) 85:53–65. https://doi.org/10.1097/01.md.0000200166.90373.41

    Article  Google Scholar 

  41. Bullen CL, Liesegang TJ, McDonald TJ, DeRemee RA (1983) Ocular complications of Wegener’s granulomatosis. Ophthalmology 90:279–290

    Article  CAS  Google Scholar 

  42. Perry SR, Rootman J, White VA (1997) The clinical and pathologic constellation of Wegener granulomatosis of the orbit. Ophthalmology 104:683–694

    Article  CAS  Google Scholar 

  43. Korantzopoulos P, Papaioannides D, Siogas K (2004) The heart in Wegener’s granulomatosis. Cardiology 102:7–10. https://doi.org/10.1159/000076995

    Article  Google Scholar 

  44. Deniz K, Ozşeker HS, Balas S et al (2007) Intestinal involvement in Wegener’s granulomatosis. J Gastrointestin Liver Dis 16:329–331

    Google Scholar 

  45. Guillevin L, Durand-Gasselin B, Cevallos R et al (1999) Microscopic polyangiitis: clinical and laboratory findings in eighty-five patients. Arthritis Rheum 42:421–430. https://doi.org/10.1002/1529-0131(199904)42:3%3c421::AID-ANR5%3e3.0.CO;2-6

  46. Finkielman JD, Lee AS, Hummel AM et al (2007) ANCA are detectable in nearly all patients with active severe Wegener’s granulomatosis. Am J Med 120. https://doi.org/10.1016/j.amjmed.2006.08.016

  47. Kitching AR, Anders HJ, Basu N et al (2020) ANCA-associated vasculitis. Nat Rev Dis Prim 6

  48. Hagen EC, Daha MR, Hermans J et al (1998) Diagnostic value of standardized assays for anti-neutrophil cytoplasmic antibodies in idiopathic systemic vasculitis. Kidney Int 53. https://doi.org/10.1046/j.1523-1755.1998.00807.x

  49. Jennette JC, Wilkman AS, Falk RJ (1998) Diagnostic predictive value of ANCA serology. Kidney Int 53

  50. Villiger PM, Guillevin L (2010) Microscopic polyangiitis: clinical presentation. Autoimmun Rev 9:812–819. https://doi.org/10.1016/j.autrev.2010.07.009

    Article  Google Scholar 

  51. Lauque D, Cadranel J, Lazor R et al (2000) Microscopic polyangiitis with alveolar hemorrhage. A study of 29 cases and review of the literature. Groupe d’Etudes et de Recherche sur les Maladies "Orphelines" Pulmonaires (GERM"O"P). Medicine (Baltimore) 79:222–33

    Article  CAS  Google Scholar 

  52. Schirmer JH, Wright MN, Vonthein R et al (2016) Clinical presentation and long-term outcome of 144 patients with microscopic polyangiitis in a monocentric German cohort. Rheumatology 55:71–79. https://doi.org/10.1093/rheumatology/kev286

    Article  Google Scholar 

  53. Alba MA, Flores-Suárez LF, Henderson AG et al (2017) Interstital lung disease in ANCA vasculitis. Autoimmun Rev 16

  54. Zhang W, Zhou G, Shi Q, Zhang X, Zeng XF, Zhang FC (2009) Clinical analysis of nervous system involvement in ANCA-associated systemic vasculitides. Clin Exp Rheumatol 27(1 Suppl 52):S65–S69. PMID: 19646349

  55. Niiyama S, Amoh Y, Tomita M, Katsuoka K (2008) Dermatological manifestations associated with microscopic polyangiitis. Rheumatol Int 28:593–595. https://doi.org/10.1007/s00296-007-0497-0

    Article  Google Scholar 

  56. Bacciu A, Bacciu S, Mercante G et al (2006) Ear, nose and throat manifestations of Churg-Strauss syndrome. Acta Otolaryngol 126:503–509. https://doi.org/10.1080/00016480500437435

    Article  Google Scholar 

  57. Keogh K, Specks U (2006) Churg-Strauss syndrome. Semin Respir Crit Care Med 27:148–157. https://doi.org/10.1055/s-2006-939518

    Article  Google Scholar 

  58. Dennert RM, Van Paassen P, Schalla S et al (2010) Cardiac involvement in churg-strauss syndrome. Arthritis Rheum 62:627–634

    Google Scholar 

  59. Cattaneo L, Chierici E, Pavone L et al (2007) Peripheral neuropathy in Wegener’s granulomatosis, Churg Strauss syndrome and microscopic polyangiitis. J Neurol Neurosurg Psychiatry 78:1119–1123. https://doi.org/10.1136/jnnp.2006.111013

    Article  Google Scholar 

  60. Vaglio A, Buzio C, Zwerina J (2013) Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): state of the art. Allergy 68:261–273. https://doi.org/10.1111/all.12088

    Article  CAS  Google Scholar 

  61. Sinico RA, Di Toma L, Maggiore U et al (2006) Renal involvement in Churg-Strauss syndrome. Am J Kidney Dis 47:770–779. https://doi.org/10.1053/j.ajkd.2006.01.026

    Article  Google Scholar 

  62. Sablé-Fourtassou R, Cohen P, Mahr A et al (2005) Antineutrophil cytoplasmic antibodies and the Churg-Strauss syndrome. Ann Intern Med 143:632–638

    Article  Google Scholar 

  63. Comarmond C, Pagnoux C, Khellaf M et al (2013) Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): clinical characteristics and long-term followup of the 383 patients enrolled in the French Vasculitis Study Group cohort. Arthritis Rheum 65:270–281

    Article  Google Scholar 

  64. Moosig F, Bremer JP, Hellmich B et al (2013) A vasculitis centre based management strategy leads to improved outcome in eosinophilic granulomatosis and polyangiitis (Churg-Strauss, EGPA): monocentric experiences in 150 patients. Ann Rheum Dis 72. https://doi.org/10.1136/annrheumdis-2012-201531

  65. Groh M, Pagnoux C, Baldini C et al (2015) Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA) Consensus Task Force recommendations for evaluation and management. Eur J Intern Med 26. https://doi.org/10.1016/j.ejim.2015.04.022

  66. Jennette JC, Falk RJ, Bacon PA et al (2013) 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 65:1–11. https://doi.org/10.1002/art.37715

    Article  CAS  Google Scholar 

  67. Windpessl M, Bettac EL, Gauckler P et al (2021) ANCA Status or clinical phenotype — what counts more? Curr Rheumatol Rep 23

  68. Hakroush S, Kluge IA, Ströbel P et al (2021) Systematic histological scoring reveals more prominent interstitial inflammation in myeloperoxidase-ANCA compared to proteinase 3-ANCA glomerulonephritis. J Clin Med 10:1231. https://doi.org/10.3390/jcm10061231

    Article  CAS  Google Scholar 

  69. Wu T, Shen C, Zhong Y et al (2021) Differences between myeloperoxidase-antineutrophil cytoplasmic autoantibody (ANCA) and proteinase 3-ANCA associated vasculitis: a retrospective study from a single center in China. Exp Ther Med 21. https://doi.org/10.3892/etm.2021.9993

  70. Hilhorst M, van Paassen P, Tervaert JWC, Registry Limburg Renal (2015) Proteinase 3-ANCA vasculitis versus myeloperoxidase-ANCA vasculitis. J Am Soc Nephrol 26:2314–2327. https://doi.org/10.1681/ASN.2014090903

    Article  CAS  Google Scholar 

  71. Geetha D, Specks U, Stone JH et al (2015) Rituximab versus cyclophosphamide for ANCA-associated vasculitis with renal involvement. J Am Soc Nephrol 26:976–985

    Article  CAS  Google Scholar 

  72. Wallace ZS, Stone JH (2019) Personalized medicine in ANCA-associated vasculitis ANCA specificity as the guide? Front Immunol 10:2855

    Article  CAS  Google Scholar 

  73. Vernier G, Sendid B, Poulain D, Colombel JF (2004) Relevance of serologic studies in inflammatory bowel disease. Curr. Gastroenterol. Rep. 6:482–487

    Article  Google Scholar 

  74. Olsson R, Daniels Son A, Jarnerot G et al (1991) Prevalence of primary sclerosing cholangitis in patients with ulcerative colitis

  75. Hardarson S, Labrecqu DR, Mitros FA et al (1993) Antineutrophil cytoplasmic antibody in inflammatory bowel and hepatobiliary diseases: high prevalence in ulcerative colitis, primary sclerosing cholangitis, and autoimmune hepatitis. Am J Clin Pathol 99:277–281. https://doi.org/10.1093/ajcp/99.3.277

    Article  CAS  Google Scholar 

  76. Peen E, Almer S, Bodemar G et al (1993) Anti-lactoferrin antibodies and other types of ANCA in ulcerative colitis, primary sclerosing cholangitis, and Crohn’s disease. Gut 34:56–62. https://doi.org/10.1136/gut.34.1.56

    Article  CAS  Google Scholar 

  77. Aadland E, Schrumpf E, Fausa O et al (1987) Primary sclerosing cholangitis: a long-term follow-up study. Scand J Gastroenterol 22:655–664. https://doi.org/10.3109/00365528709011139

    Article  CAS  Google Scholar 

  78. Nisihara RM, De Carvalho WB, Da Rosa Utiyama SR et al (2010) Diagnostic role and clinical association of ASCA and ANCA in Brazilian patients with inflammatory bowel disease. Dig Dis Sci 55:2309–2315. https://doi.org/10.1007/s10620-009-0998-7

    Article  Google Scholar 

  79. Saibeni S, Folli C, de Franchis R et al (2003) Diagnostic role and clinical correlates of anti-Saccharomyces cerevisiae antibodies (ASCA) and anti-neutrophil cytoplasmic antibodies (p-ANCA) in Italian patients with inflammatory bowel diseases. Dig Liver Dis 35:862–868. https://doi.org/10.1016/j.dld.2003.07.001

    Article  CAS  Google Scholar 

  80. Damoiseaux JGMC, Bouten B, Linders AMLW et al (2002) Diagnostic value of anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies for inflammatory bowel disease: high prevalence in patients with celiac disease. J Clin Immunol 22:281–288. https://doi.org/10.1023/A:1019926121972

    Article  CAS  Google Scholar 

  81. Quinton J-F, Sendid B, Reumaux D et al (1998) Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role. Gut 42:788–791. https://doi.org/10.1136/gut.42.6.788

    Article  CAS  Google Scholar 

  82. Prideaux L, De Cruz P, Ng SC, Kamm MA (2012) Serological antibodies in inflammatory bowel disease: a systematic review. Inflamm Bowel Dis 18:1340–1355

    Article  Google Scholar 

  83. Maaser C, Sturm A, Vavricka SR et al (2019) ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: initial diagnosis, monitoring of known IBD, detection of complications. J Crohn’s Colitis 13:144–164. https://doi.org/10.1093/ecco-jcc/jjy113

    Article  Google Scholar 

  84. Lee WI, Subramaniam K, Hawkins CA, Randall KL (2019) The significance of ANCA positivity in patients with inflammatory bowel disease. Pathology 51:634–639. https://doi.org/10.1016/j.pathol.2019.07.002

    Article  Google Scholar 

  85. Thurgate LE, Lemberg DA, Day AS, Leach ST (2019) An overview of inflammatory bowel disease unclassified in children. Inflamm Intest Dis 4:97–103. https://doi.org/10.1159/000501519

    Article  Google Scholar 

  86. Horn MP, Peter AM, Grunder FR et al (2018) PR3-ANCA and panel diagnostics in pediatric inflammatory bowel disease to distinguish ulcerative colitis from Crohn’s disease PLoS One 13. https://doi.org/10.1371/journal.pone.0208974

  87. Tremaine WJ (2011) Diagnosis and treatment of indeterminate colitis. Gastroenterol Hepatol (N Y) 7:826–828

    Google Scholar 

  88. Bossuyt X (2005) Serologic markers in inflammatory bowel disease. Clin Chem 52:171–181. https://doi.org/10.1373/clinchem.2005.058560

    Article  CAS  Google Scholar 

  89. Birimberg-Schwartz L, Wilson DC, Kolho KL et al (2016) PANCA and ASCA in children with IBD-unclassified, Crohn’s colitis, and ulcerative colitis - a longitudinal report from the IBD Porto Group of ESPGHAN. Inflamm Bowel Dis 22:1908–1914. https://doi.org/10.1097/MIB.0000000000000784

    Article  Google Scholar 

  90. Arias-Loste MT, Bonilla G, Moraleja I et al (2013) Presence of anti-proteinase 3 antineutrophil cytoplasmic antibodies (Anti-PR3 ANCA) as serologic markers in inflammatory bowel disease. Clin Rev Allergy Immunol 45:109–116. https://doi.org/10.1007/s12016-012-8349-4

    Article  CAS  Google Scholar 

  91. Mahler M, Bogdanos DP, Pavlidis P et al (2013) PR3-ANCA: a promising biomarker for ulcerative colitis with extensive disease. Clin Chim Acta 424:267–273. https://doi.org/10.1016/j.cca.2013.06.005

    Article  CAS  Google Scholar 

  92. Van Biervliet S, Bonroy C, Vande Velde S et al (2013) C-ANCA/proteinase 3-positive colitis in children: a distinctive form of inflammatory bowel disease or vasculitis with colitis as initial presentation? J Pediatr Gastroenterol Nutr 57:489–492. https://doi.org/10.1097/MPG.0b013e31829d4e9e

    Article  CAS  Google Scholar 

  93. Stinton L, Kaplan G, Mahler M et al (2013) Proteinase 3 (PR3) autoantibodies as a serological marker in inflammatory bowel disease (IBD). Am J Gastroenterol

  94. Stinton LM, Bentow C, Mahler M et al (2014) PR3-ANCA: a promising biomarker in primary sclerosing cholangitis (PSC). PLoS One 9:e112877. https://doi.org/10.1371/journal.pone.0112877

    Article  CAS  Google Scholar 

  95. Mahler M, Damoiseaux J, Ballet V et al (2017) PR3-anti-neutrophil cytoplasmic antibodies (ANCA) in ulcerative colitis. Clin Chem Lab Med 56:e27–e30

    Article  Google Scholar 

  96. Takedatsu H, Mitsuyama K, Fukunaga S et al (2018) Diagnostic and clinical role of serum proteinase 3 antineutrophil cytoplasmic antibodies in inflammatory bowel disease. J Gastroenterol Hepatol 33:1603–1607. https://doi.org/10.1111/jgh.14140

    Article  CAS  Google Scholar 

  97. Trivedi PJ, Hubscher SG, Heneghan M et al (2019) Grand round: autoimmune hepatitis. J Hepatol 70:773–784. https://doi.org/10.1016/j.jhep.2018.11.006

    Article  Google Scholar 

  98. Lohse AW, Chazouillères O, Dalekos G et al (2015) EASL clinical practice guidelines: autoimmune hepatitis. J Hepatol 63:971–1004. https://doi.org/10.1016/j.jhep.2015.06.030

    Article  Google Scholar 

  99. Toda G, Zeniya M (1993) Autoimmune hepatitis. Intern Med 32:913–916

    Article  CAS  Google Scholar 

  100. Mulder AHL, Horst G, Haagsma EB et al (1993) Prevalence and characterization of neutrophil cytoplasmic antibodies in autoimmune liver diseases. Hepatology 17:411–417. https://doi.org/10.1002/hep.1840170310

    Article  CAS  Google Scholar 

  101. Zauli D, Ghetti S, Grassi A et al (1997) Anti-neutrophilcytoplasmic antibodies in type 1 and 2 autoimmune hepatitis. Hepatology 25:1105–1107. https://doi.org/10.1002/hep.510250510

    Article  CAS  Google Scholar 

  102. Targan SR, Landers C, Vidrich A, Czaja AJ (1995) High-titer antineutrophil cytoplasmic antibodies in type-1 autoimmune hepatitis. Gastroenterology 108:1159–1166. https://doi.org/10.1016/0016-5085(95)90215-5

    Article  CAS  Google Scholar 

  103. Vergani D, Alvarez F, Bianchi FB et al (2004) Liver autoimmune serology: a consensus statement from the committee for autoimmune serology of the International Autoimmune Hepatitis Group. J Hepatol 41:677–683

    Article  Google Scholar 

  104. Terjung B, Spengler U, Sauerbruch T, Worman HJ (2000) “Atypical p-ANCA” in IBD and hepatobiliary disorders react with a 50-kilodalton nuclear envelope protein of neutrophils and myeloid cell lines. Gastroenterology 119:310–322. https://doi.org/10.1053/gast.2000.9366

    Article  CAS  Google Scholar 

  105. Terziroli Beretta-Piccoli B, Mieli-Vergani G, Vergani D (2018) Serology in autoimmune hepatitis: a clinical-practice approach. Eur J Intern Med 48:35–43. https://doi.org/10.1016/j.ejim.2017.10.006

    Article  CAS  Google Scholar 

  106. Nicoletti A, Maurice JB, Thorburn D (2021) Guideline review: British Society of Gastroenterology/UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis. Front Gastroenterol 12:62–66

    Article  Google Scholar 

  107. Terjung B, Spengler U (2005) Role of auto-antibodies for the diagnosis of chronic cholestatic liver diseases. Clin Rev Allergy Immunol 28:115–133

    Article  CAS  Google Scholar 

  108. Lo SK, Fleming KA, Chapman RW (1994) A 2-year follow-up study of anti-neutrophil antibody in primary sclerosing cholangitis: relationship to clinical activity, liver biochemistry and ursodeoxycholic acid treatment. J Hepatol 21:974–978. https://doi.org/10.1016/S0168-8278(05)80604-X

    Article  CAS  Google Scholar 

  109. Hov JR, Boberg KM, Taraldsrud E et al (2017) Antineutrophil antibodies define clinical and genetic subgroups in primary sclerosing cholangitis. Liver Int 37:458–465. https://doi.org/10.1111/liv.13238

    Article  CAS  Google Scholar 

  110. Wunsch E, Norman GL, Milkiewicz M et al (2021) Anti-glycoprotein 2 (anti-GP2) IgA and anti-neutrophil cytoplasmic antibodies to serine proteinase 3 (PR3-ANCA): antibodies to predict severe disease, poor survival and cholangiocarcinoma in primary sclerosing cholangitis. Aliment Pharmacol Ther 53:302–313. https://doi.org/10.1111/apt.16153

    Article  CAS  Google Scholar 

  111. Borchers AT, Leibushor N, Naguwa SM et al (2012) Lupus nephritis: a critical review. Autoimmun Rev 12:174–194

    Article  Google Scholar 

  112. Sen D, Isenberg DA (2003) Antineutrophil cytoplasmic autoantibodies in systemic lupus erythematosus. Lupus 12:651–658

    Article  CAS  Google Scholar 

  113. Barile-Fabris L, Hernández-Cabrera MF, Barragan-Garfias JA (2014) Vasculitis in systemic lupus erythematosus. Curr Rheumatol Rep 16. https://doi.org/10.1007/s11926-014-0440-9

  114. Mirza R, Urowitz M, Su J GD (2020) ANCA in SLE: prevalence and predictor factors - ACR meeting abstracts. In Arthritis Rheumatol. https://acrabstracts.org/abstract/anca-in-sle-prevalence-and-predictor-factors/

  115. Wang Y, Huang X, Cai J et al (2016) Clinicopathologic characteristics and outcomes of lupus nephritis with antineutrophil cytoplasmic antibody: a retrospective study. Medicine (United States) 95. https://doi.org/10.1097/MD.0000000000002580

  116. Manolova I, Dancheva M, Halacheva K (2001) Antineutrophil cytoplasmic antibodies in patients with systemic lupus erythematosus: prevalence, antigen specificity, and clinical associations. Rheumatol Int 20:197–204. https://doi.org/10.1007/s002960100108

    Article  CAS  Google Scholar 

  117. Galeazzi M, Morozzi G, Sebastiani GD, Bellisai F, Marcolongo R, Cervera R, De Ramòn Garrido E, Fernandez-Nebro A, Houssiau F, Jedryka-Goral A, Mathieu A, Papasteriades C, Piette JC, Scorza R, Smolen J (1998) Anti-neutrophil cytoplasmic antibodies in 566 European patients with systemic lupus erythematosus: prevalence, clinical associations and correlation with other autoantibodies. European Concerted Action on the Immunogenetics of SLE. Clin Exp Rheumatol 16(5):541–546. PMID: 9779300

  118. Ramaswami A, Kandaswamy T, Rajendran T et al (2008) Scleroderma with crescentic glomerulonephritis: a case report. J Med Case Rep 2. https://doi.org/10.1186/1752-1947-2-151

  119. Varga J, Abraham D (2007) Systemic sclerosis: a prototypic multisystem fibrotic disorder. J Clin Invest 117

  120. Shanmugam VK, Steen VD (2012) Renal disease in scleroderma: an update on evaluation, risk stratification, pathogenesis and management. Curr Opin Rheumatol 24

  121. Chung L, Utz PJ (2004) Antibodies in scleroderma: direct pathogenicity and phenotypic associations. Curr Rheumatol Rep 6:156–163

    Article  Google Scholar 

  122. Caramaschi P, Biasi D, Tonolli E et al (2002) Antineutrophil cytoplasmic antibodies in scleroderma patients: first report of a case with anti-proteinase 3 antibodies and review of the literature. Jt Bone Spine 69:177–180. https://doi.org/10.1016/S1297-319X(02)00367-6

    Article  Google Scholar 

  123. Quéméneur T, Mouthon L, Cacoub P et al (2013) Systemic vasculitis during the course of systemic sclerosis: report of 12 cases and review of the literature. Medicine (United States) 92:1–9

    Google Scholar 

  124. Moxey J, Huq M, Proudman S et al (2019) Significance of anti-neutrophil cytoplasmic antibodies in systemic sclerosis. Arthritis Res Ther 21:1–12. https://doi.org/10.1186/s13075-019-1839-5

    Article  Google Scholar 

  125. Derrett-Smith EC, Nihtyanova SI, Harvey J et al (2013) Revisiting ANCA-associated vasculitis in systemic sclerosis: clinical, serological and immunogenetic factors. Rheumatology (United Kingdom) 52:1824–1831. https://doi.org/10.1093/rheumatology/ket213

    Article  CAS  Google Scholar 

  126. Arad U, Balbir-Gurman A, Doenyas-Barak K et al (2011) Anti-neutrophil antibody associated vasculitis in systemic sclerosis. Semin Arthritis Rheum 41. https://doi.org/10.1016/j.semarthrit.2010.11.001

  127. Young HR, Seong JC, Young HL et al (2006) Scleroderma associated with ANCA-associated vasculitis. Rheumatol Int 26

  128. Liang KP, Michet CJ (2011) ANCA-associated vasculitis in scleroderma: a case series of fourteen patients. Rheumatol Rep 3

  129. Brito-Zerón P, Baldini C, Bootsma H et al (2016) Sjögren syndrome. Nat Rev Dis Prim 2:1–20. https://doi.org/10.1038/nrdp.2016.47

    Article  Google Scholar 

  130. Fayyaz A, Kurien BT, Scofield RH (2016) Autoantibodies in Sjögren’s syndrome. Rheum Dis Clin North Am 42

  131. Ramos-Casals M, Nardi N, Brito-Zerón P et al (2006) Atypical autoantibodies in patients with primary Sjögren syndrome: clinical characteristics and follow-up of 82 cases. Semin Arthritis Rheum 35. https://doi.org/10.1016/j.semarthrit.2005.12.004

  132. Ramos-Casals M, Solans R, Rosas J et al (2008) Primary Sjögren syndrome in Spain: clinical and immunologic expression in 1010 patients. Medicine (Baltimore) 87. https://doi.org/10.1097/MD.0b013e318181e6af

  133. Specks U, Wiegert EM, Homburger HA (1997) Human mast cells expressing recombinant proteinase 3 (PR3) as substrate for clinical testing for anti-neutrophil cytoplasmic antibodies (ANCA). Clin Exp Immunol 109. https://doi.org/10.1046/j.1365-2249.1997.4561353.x

  134. Noel N, André C, Bengoufa D et al (2013) Performance evaluation of three assays for the detection of PR3-ANCA in granulomatosis with polyangiitis in daily practice. Autoimmun Rev 12

  135. Lee IH, Kim SK, Kim MK (2016) Dual anti-neutrophil cytoplasmic antibody-related pauci-immune crescentic glomerulonephritis in a patient with Sjögren’s syndrome. Rheumatol Int 36

  136. Morimoto C, Fujigaki Y Tamura Y et al (2018) Emergence of smoldering ANCA-associated glomerulonephritis during the clinical course of mixed connective tissue disease and sjögren’s syndrome. Intern Med 57. https://doi.org/10.2169/internalmedicine.9844-17

  137. Hsu CW, Su YJ, Chang WN et al (2014) The association between serological biomarkers and primary Sjogren’s syndrome associated with peripheral polyneuropathy. Biomed Res Int 2014. https://doi.org/10.1155/2014/902492

  138. Guellec D, Cornec-Le Gall E, Groh M et al (2015) ANCA-associated vasculitis in patients with primary Sjögren’s syndrome: detailed analysis of 7 new cases and systematic literature review. Autoimmun Rev 14

  139. Lee S, Bin H, Choi MK, Kim et al (2020) Can antineutrophil cytoplasmic antibody positivity at diagnosis predict the poor outcomes of Sjögren’s syndrome? Rheumatol Int 40 https://doi.org/10.1007/s00296-019-04476-5

  140. Font J, Ramos-Casals M, Cervera R et al (1998) Antineutrophil cytoplasmic antibodies in primary Sjogren’s syndrome: prevalence and clinical significance. Br J Rheumatol 37. https://doi.org/10.1093/rheumatology/37.12.1287

  141. Stone JH, Zen Y, Deshpande V (2012) Mechanisms of disease: IgG4-related disease. N Engl J Med 366. https://doi.org/10.1056/NEJMra1104650

  142. Maritati F, Peyronel F, Vaglio A (2020) IgG4-related disease: a clinical perspective. Rheumatology (United Kingdom) 59

  143. Lin W, Lu S, Chen H et al (2015) Clinical characteristics of immunoglobulin G4-related disease: a prospective study of 118 Chinese patients. Rheumatology (United Kingdom) 54. https://doi.org/10.1093/rheumatology/kev203

  144. Umehara H, Okazaki K, Masaki Y et al (2012) Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol 22. https://doi.org/10.1007/s10165-011-0571-z

  145. Carruthers MN, Khosroshahi A, Augustin T et al (2015) The diagnostic utility of serum IgG4 concentrations in IgG4-related disease. Ann Rheum Dis 74. https://doi.org/10.1136/annrheumdis-2013-204907

  146. Sekiguchi H, Horie R, Kanai M et al (2016) IgG4-related disease: retrospective analysis of one hundred sixty-six patients. Arthritis Rheumatol 68. https://doi.org/10.1002/art.39686

  147. Erden A, Bolek EC, Yardimci KG et al (2019) Do ANCA-associated vasculitides and IgG4-related disease really overlap or not? Int J Rheum Dis 22. https://doi.org/10.1111/1756-185X.13693

  148. Martín-Nares E, Zuñiga-Tamayo D, Hinojosa-Azaola A (2019) Prevalence of overlap of antineutrophil cytoplasmic antibody associated vasculitis with systemic autoimmune diseases: an unrecognized example of poliautoimmunity. Clin Rheumatol 38. https://doi.org/10.1007/s10067-018-4212-1

  149. Detlefsen S, Vos De JD, Tanassi JT et al (2018) Value of anti-plasminogen binding peptide, anticarbonic anhydrase II, immunoglobulin G4, and other serological markers for the differentiation of autoimmune pancreatitis and pancreatic cancer. Medicine (United States) 97. https://doi.org/10.1097/MD.0000000000011641

  150. Mustila A, Paimela L, Leirisalo-Repo M et al (2000) Antineutrophil cytoplasmic antibodies in patients with early rheumatoid arthritis: an early marker of progressive erosive disease. Arthritis Rheum 43. https://doi.org/10.1002/1529-0131(200006)43:6/1371::AID-ANR22/3.0.CO;2-R

  151. Braun MG, Csernok E, Schmitt WH, Gross WL (1996) Incidence, target antigens, and clinical implications of antineutrophil cytoplasmic antibodies in rheumatoid arthritis. J Rheumatol 23

  152. Mandl LA, Solomon DH, Smith EL et al (2002) Using antineutrophil cytoplasmic antibody testing to diagnose vasculitis: can test-ordering guidelines improve diagnostic accuracy? Arch Intern Med 162. https://doi.org/10.1001/archinte.162.13.1509

  153. Mustila A, Korpel M, Mustonen J et al (1997) Perinuclear antineutrophil cytoplasmic antibody in rheumatoid arthritis: a marker of severe disease with associated nephropathy. 40:710–717

    Article  CAS  Google Scholar 

  154. Voskuyl AE, Hazes JMW, Zwinderman AH et al (2003) Diagnostic strategy for the assessment of rheumatoid vasculitis. Ann Rheum Dis 62. https://doi.org/10.1136/ard.62.5.407

  155. Kida I, Kobayashi S, Takeuchi K et al (2011) Antineutrophil cytoplasmic antibodies against myeloperoxidase, proteinase 3, elastase, cathepsin G and lactoferrin in Japanese patients with rheumatoid arthritis. Mod Rheumatol 21. https://doi.org/10.1007/s10165-010-0356-9

  156. Bosch X, Llena J, Collado A et al (1995) Occurrence of antineutrophil cytoplasmic and antineutrophil (peri)nuclear antibodies in rheumatoid arthritis. J Rheumatol 22

  157. Chinoy H, McKenna F (2002) Wegener’s granulomatosis and rheumatoid arthritis overlap [3]. Rheumatology 41

  158. Pagnoux C, Seror R, Bérezné A et al (2010) Remittent non-destructive polysynovitis in P-ANCA-positive vasculitis patients with anti-CCP antibodies. Jt Bone Spine 77. https://doi.org/10.1016/j.jbspin.2010.02.013

  159. Röther E, Schochat T, Peter HH (1996) Antineutrophil cytoplasmic antibodies (ANCA) in rheumatoid arthritis: a prospective study. Rheumatol Int 15. https://doi.org/10.1007/BF00290376

  160. Ramos-Casals M, Brito-Zerón P, Soto MJ et al (2008) Autoimmune diseases induced by TNF-targeted therapies. Best Pract Res Clin Rheumatol 22

  161. Spoerl D, Pers YM, Jorgensen C (2012) Anti-neutrophil cytoplasmic antibodies in rheumatoid arthritis: two case reports and review of literature. Allergy Asthma Clin Immunol 8. https://doi.org/10.1186/1710-1492-8-19

  162. Ramos-Casals M, Jara LJ, Medina F et al (2005) Systemic autoimmune diseases co-existing with chronic hepatitis C virus infection (the HISPAMEC Registry): patterns of clinical and immunological expression in 180 cases. J Intern Med 257. https://doi.org/10.1111/j.1365-2796.2005.01490.x

  163. Asherson RA, Cervera R (2003) Antiphospholipid antibodies and infections. Ann Rheum Dis 62

  164. Choi HK, Lamprecht P, Niles JL et al (2000) Subacute bacterial endocarditis with positive cytoplasmic antineutrophil cytoplasmic antibodies and anti-proteinase 3 antibodies. Arthritis Rheum 43. https://doi.org/10.1002/1529-0131(200001)43:1/226::AID-ANR27/3.0.CO;2-Q

  165. 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):606. https://doi.org/10.1136/bmj.285.6342.606. PMID: 6297657; PMCID: PMC1499415

  166. Guillevin L, Lhote F, Ghérardi R (1997) The spectrum and treatment of virus-associated vasculitides. Curr Opin Rheumatol 9

  167. Schmitt WH, Van Der Woude FJ (2004) Clinical applications of antineutrophil cytoplasmic antibody testing. Curr Opin Rheumatol 16

  168. Zeledon JI, McKelvey RL, Servilla KS et al (2008) Glomerulonephritis causing acute renal failure during the course of bacterial infections. Histological varieties, potential pathogenetic pathways and treatment. Int Urol Nephrol 40. https://doi.org/10.1007/s11255-007-9323-6

  169. Wu YY, Hsu TC, Chen TY et al (2002) Proteinase 3 and dihydrolipoamide dehydrogenase (E3) are major autoantigens in hepatitis C virus (HCV) infection. Clin Exp Immunol 128. https://doi.org/10.1046/j.1365-2249.2002.01827.x

  170. Chou TN, Hsu TC, Chen RM et al (2000) Parvovirus B19 infection associated with the production of anti-neutrophil cytoplasmic antibody (ANCA) and anticardiolipin antibody (aCL). Lupus 9:551–554. https://doi.org/10.1177/096120330000900714

    Article  CAS  Google Scholar 

  171. Chan B, d’Intini V, Savige J (2006) Anti-neutrophil cytoplasmic antibody (ANCA)-associated microscopic polyangiitis following a suppurative wound infection [8]. Nephrol Dial Transplant 21

  172. Papayannopoulos V, Zychlinsky A (2009) NETs: a new strategy for using old weapons. Trends Immunol 30

  173. Popa ER, Stegeman CA, Abdulahad WH et al (2007) Staphylococcal toxic-shock-syndrome-toxin-1 as a risk factor for disease relapse in Wegener’s granulomatosis. Rheumatology 46 https://doi.org/10.1093/rheumatology/kem022

  174. Kallenberg CGM, Tadema H (2008) Vasculitis and infections: contribution to the issue of autoimmunity reviews devoted to “autoimmunity and infection.” Autoimmun Rev 8

  175. Tidman M, Olander R, Svalander C, Danielsson D (1998) Patients hospitalized because of small vessel vasculitides with renal involvement in the period 1975–95: organ involvement, anti-neutrophil cytoplasmic antibodies patterns, seasonal attack rates and fluctuation of annual frequencies. J Intern Med 244. https://doi.org/10.1046/j.1365-2796.1998.00324.x

  176. Nässberger L, Johansson A-C, Björck S, Sjöholm AG (1991) Antibodies to neutrophil granulocyte myeloperoxidase and elastase: autoimmune responses in glomerulonephritis due to hydralazine treatment. J Intern Med 229. https://doi.org/10.1111/j.1365-2796.1991.tb00342.x

  177. Almroth G, Eneström S Hed J et al (1992) Autoantibodies to leucocyte antigens in hydralazine-associated nephritis. J Intern Med 231. https://doi.org/10.1111/j.1365-2796.1992.tb00496.x

  178. StokesMB, Foster K, Markowitz GS et al (2005) Development of glomerulonephritis during anti-TNF-alpha; therapy for rheumatoid arthritis. Nephrol Dial Transplant 20. https://doi.org/10.1093/ndt/gfh832

  179. Simms R, Kipgen D, Dahill S et al (2008) ANCA-associated renal vasculitis following anti-tumor necrosis factor α therapy. Am J Kidney Dis 51. https://doi.org/10.1053/j.ajkd.2007.10.043

  180. Bienaimé F, Clerbaux G, Plaisier E et al (2007) d-Penicillamine-induced ANCA-associated crescentic glomerulonephritis in Wilson disease. Am J Kidney Dis 50. https://doi.org/10.1053/j.ajkd.2007.05.026

  181. Locke IC, Worrall JG, Leaker B et al (1997) Autoantibodies to myeloperoxidase in systemic sclerosis. J Rheumatol 24

  182. Salerno SM, Ormseth EJ, Roth BJ et al (1996) Sulfasalazine pulmonary toxicity in ulcerative colitis mimicking clinical features of Wegener’s granulomatosis. Chest 110. https://doi.org/10.1378/chest.110.2.556

  183. Denissen NHAM, Peters JGP, Masereeuw R, Barrera P (2008) Can sulfasalazine therapy induce or exacerbate Wegener’s granulomatosis? Scand J Rheumatol 37. https://doi.org/10.1080/03009740701607117

  184. Sethi S, Sahani M, Oei LS (2003) ANCA-positive crescentic glomerulonephritis associated with minocycline therapy. Am J Kidney Dis 42. https://doi.org/10.1016/s0272-6386(03)00671-1

  185. Gao Y, Zhao MH, Guo XH et al (2004) The prevalence and target antigens of antithyroid drugs induced antineutrophil cytoplasmic antibodies (ANCA) in Chinese patients with hyperthyroidism. Endocr Res 30. https://doi.org/10.1081/ERC-120037729

  186. Cambridge G, Wallace H, Bernstein RM, Leaker B (1994) Autoantibodies to myeloperoxidase in idiopathic and drug-induced systemic lupus erythematosus and vasculitis. Rheumatology 33. https://doi.org/10.1093/rheumatology/33.2.109

  187. Gao Y, Chen M, Ye H et al (2007) The target antigens of antineutrophil cytoplasmic antibodies (ANCA) induced by propylthiouracil. Int Immunopharmacol 7. https://doi.org/10.1016/j.intimp.2006.07.033

  188. Chen YX, Yu HJ, Ni LY et al (2007) Propylthiouracil-associated antineutrophil cytoplasmic autoantibody- positive vasculitis: Retrospective study of 19 cases. J Rheumatol 34

  189. Martin DB, Deng A, Gaspari A, Pearson F (2006) Perinuclear antineutrophil cytoplasmic antibody-associated vasculitis in a patient with Graves’ disease treated with methimazole. Skinmed 5. https://doi.org/10.1111/j.1540-9740.2006.05350.x

  190. Calañas-Continente A, Espinosa M, Manzano-García G et al (2005) Necrotizing glomerulonephritis and pulmonary hemorrhage associated with carbimazole therapy. Thyroid 15. https://doi.org/10.1089/thy.2005.15.286

  191. Hachicha M, Kammoun T, Romdhane WB et al (2007) Vasculitis with renal involvement andantineutrophil cytoplasmic antibodies (ANCA) inachild receiving benzylthiouracil. Nephrol Ther 3. https://doi.org/10.1016/j.nephro.2007.04.001

  192. Gao Y, Ye H, Yu F et al (2005) Anti-myeloperoxidase IgG subclass distribution and avidity in sera from patients with propylthiouracil-induced antineutrophil cytoplasmic antibodies associated vasculitis. Clin Immunol 117. https://doi.org/10.1016/j.clim.2005.06.002

  193. Schroeder JW, Folci M, Losappio LM et al (2019) Anti-neutrophil cytoplasmic antibodies positivity and anti-leukotrienes in eosinophilic granulomatosis with polyangiitis: a retrospective monocentric study on 134 Italian patients. Int Arch Allergy Immunol 180:64–71

    Article  CAS  Google Scholar 

  194. Graf J (2013) Rheumatic manifestations of cocaine use. Curr Opin Rheumatol 25

  195. Trimarchi M, Bussi M, Sinico RA et al (2013) Cocaine-induced midline destructive lesions - an autoimmune disease? Autoimmun Rev 12:496–500

    Article  CAS  Google Scholar 

  196. McGrath MM, Isakova T, Rennke HG et al (2011) Contaminated cocaine and antineutrophil cytoplasmic antibody-associated disease. Clin J Am Soc Nephrol 6:2799–2805. https://doi.org/10.2215/CJN.03440411

    Article  Google Scholar 

  197. Orriols R, Muñoz X, Ferrer J et al (1996) Cocaine-induced Churg-Strauss vasculitis. Eur Respir J 9. https://doi.org/10.1183/09031936.96.09010175

  198. Pendergraft WF, Niles JL (2014) Trojan horses: drug culprits associated with antineutrophil cytoplasmic autoantibody (ANCA) vasculitis. Curr Opin Rheumatol 26

  199. Choi HK, Merkel PA, Walker AM, Niles JL (2000) Drug-associated antineutrophil cytoplasmic antibody–positive vasculitis: prevalence among patients with high titers of antimyeloperoxidase antibodies. Arthritis Rheum 43:405. https://doi.org/10.1002/1529-0131(200002)43:2%3c405::AID-ANR22%3e3.0.CO;2-5

    Article  CAS  Google Scholar 

  200. Racanelli V, Prete M, Minoia C et al (2008) Rheumatic disorders as paraneoplastic syndromes. Autoimmun Rev 7:352–358

    Article  Google Scholar 

  201. Hamidou MA, El Kouri D, Audrain M, Grolleau JY (2001) Systemic antineutrophil cytoplasmic antibody vasculitis associated with lymphoid neoplasia. Ann Rheum Dis 60:293–295

    Article  CAS  Google Scholar 

  202. Miyata KN, Siddiqi NA, Kiss LP et al (2017) Antineutrophil cytoplasmic antibody-positive pauci-immune glomerulonephritis associated with mantle cell lymphoma. Clin Nephrol Case Stud 5:9–15

    Article  Google Scholar 

  203. Wills Sanín B, Bolivar YRC, Carvajal JJ et al (2014) Polyangiitis with granulomatosis as a paraneoplastic syndrome of B-cell lymphoma of the lacrimal gland. Case Rep Hematol 2014:713048

  204. Tamoto Y, Ishida R, Shiogama K et al (2017) Extranodal NK/T-cell lymphoma, nasal type accompanied by PR3-ANCA-associated glomerulonephritis. Intern Med 56:2007–2012

    Article  Google Scholar 

  205. Jayachandran NV, Thomas J, Chandrasekhara PKS et al (2009) Cutaneous vasculitis as a presenting manifestation of acute myeloid leukemia. Int J Rheum Dis 12:70–73

    Article  Google Scholar 

  206. Philipponnet C, Garrouste C, Le Guenno G et al (2017) Antineutrophilic cytoplasmic antibody-associated vasculitis and malignant hemopathies, a retrospective study of 16 cases. Joint Bone Spine 84:51–57

    Article  Google Scholar 

  207. Folci M, Ramponi G, Shiffer D et al (2019) ANCA-associated vasculitides and hematologic malignancies: lessons from the past and future perspectives. J Immunol Res 2019:1–9. https://doi.org/10.1155/2019/1732175

    Article  CAS  Google Scholar 

  208. Godbole MS, Valenzuela R, Deodhar SD et al (1995) Comparative study of ELISA and indirect immunofluorescence for the detection of anti-neutrophil cytoplasmic antibodies. Evaluation of the SCIMEDX/EURO Diagnostica ELISA assay in a clinical setting. Am J Clin Pathol 104:667–672

    Article  CAS  Google Scholar 

  209. Shang W, Ning Y, Xu X et al (2015) Incidence of cancer in ANCA-associated vasculitis: a meta-analysis of observational studies. PLoS One 10:e0126016

  210. Bachireddy P, Burkhardt UE, Rajasagi M, Wu CJ (2015) Haematological malignancies: at the forefront of immunotherapeutic innovation. Nat Rev Cancer 15:201–15

    Article  CAS  Google Scholar 

  211. Dengler R, Münstermann U, al-Batran S et al (1995) Immunocytochemical and flow cytometric detection of proteinase 3 (myeloblastin) in normal and leukaemic myeloid cells. Br J Haematol 89:250–7

    Article  CAS  Google Scholar 

  212. Ye B, Stary CM, Gao Q et al (2017) Genetically modified T-cell-based adoptive immunotherapy in hematological malignancies. J Immunol Res 2017:1–13

    Google Scholar 

  213. Qazilbash MH, Wieder E, Thall PF et al (2017) PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies. Leukemia 31:697–704

    Article  CAS  Google Scholar 

  214. Sergeeva A, Alatrash G, He H et al (2011) An anti-PR1/HLA-A2 T-cell receptor-like antibody mediates complement-dependent cytotoxicity against acute myeloid leukemia progenitor cells. Blood 117:4262–72

    Article  CAS  Google Scholar 

  215. Alatrash G, Molldrem JJ, Qazilbas MH (2018) Targeting PR1 in myeloid leukemia. Oncotarget 9:4280–4281

    Article  Google Scholar 

  216. Grönwall C, Silverman GJ (2014) Natural IgM: beneficial autoantibodies for the control of inflammatory and autoimmune disease. J Clin Immunol 34

  217. Lacroix-Desmazes S, Kaveri SV, Mouthon L et al (1998) Self-reactive antibodies (natural autoantibodies) in healthy individuals. J Immunol Methods 216. https://doi.org/10.1016/S0022-1759(98)00074-X

  218. Cui Z, Zhao M-H, Segelmark M, Hellmark T (2010) Natural autoantibodies to myeloperoxidase, proteinase 3, and the glomerular basement membrane are present in normal individuals. Kidney Int 78:590–597. https://doi.org/10.1038/ki.2010.198

    Article  CAS  Google Scholar 

  219. Jeffs L, Peh C, Nelson A et al (2019) IgM ANCA in healthy individuals and in patients with ANCA-associated vasculitis. Immunol Res 67. https://doi.org/10.1007/s12026-019-09091-x

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marco Folci.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Folci, M., Ramponi, G., Solitano, V. et al. Serum ANCA as Disease Biomarkers: Clinical Implications Beyond Vasculitis. Clinic Rev Allerg Immunol 63, 107–123 (2022). https://doi.org/10.1007/s12016-021-08887-w

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12016-021-08887-w

Keywords

Navigation