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Clin Exp Immunol. 1991 Mar; 83(3): 379–386.
PMCID: PMC1535341

Predominance of IgG1 and IgG4 subclasses of anti-neutrophil cytoplasmic autoantibodies (ANCA) in patients with Wegener's granulomatosis and clinically related disorders.


In view of the supposed hypersensitivity, the elevated levels of IgE, and the occurrence of eosinophilia reported in Wegener's granulomatosis and related conditions, we studied the IgG subclass distribution of ANCA directed against a 29-kD serine protease and myeloperoxidase (MPO) in 41 untreated ANCA-positive patients with several forms of active vasculitis and/or glomerulonephritis. We found that both 29-kD ANCA and MPO ANCA were predominantly of the IgG1 and IgG4 subclass in all groups of patients. The additional presence of IgG3 subclass was associated with renal involvement. We compared the subclass distribution of ANCA with that of total IgG subclass levels, and with the IgG subclass distribution of antibodies to cytomegalovirus (CMV) as a persistent endogenous antigen and antibodies to tetanus toxoid (TT) as an exogenous recall antigen. Total levels of IgG4 were elevated in the majority of the patients together with elevated IgG1 levels. Antibodies to CMV and TT, however, had the same subclass distribution as found in normals and did not show enhanced IgG4 expression. ANCA belong predominantly to the IgG1 and IgG4 subclass, which may suggest that the production of ANCA is related to recurrent exposition to the antigen(s) involved, possibly as part of a hypersensitivity reaction.

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  • Aalberse RC, van der Gaag R, van Leeuwen J. Serologic aspects of IgG4 antibodies. I. Prolonged immunization results in an IgG4-restricted response. J Immunol. 1983 Feb;130(2):722–726. [PubMed]
  • Bird P, Calvert JE, Amlot PL. Distinctive development of IgG4 subclass antibodies in the primary and secondary responses to keyhole limpet haemocyanin in man. Immunology. 1990 Mar;69(3):355–360. [PMC free article] [PubMed]
  • Boey H, Rosenbaum R, Castracane J, Borish L. Interleukin-4 is a neutrophil activator. J Allergy Clin Immunol. 1989 May;83(5):978–984. [PubMed]
  • Bowman C, Ambrus K, Lockwood CM. Restriction of human IgG subclass expression in the population of auto-antibodies to glomerular basement membrane. Clin Exp Immunol. 1987 Aug;69(2):341–349. [PMC free article] [PubMed]
  • Carrington CB, Liebow A. Limited forms of angiitis and granulomatosis of Wegener's type. Am J Med. 1966 Oct;41(4):497–527. [PubMed]
  • Tervaert JW, van der Woude FJ, Kallenberg CG. Analyse van de symptomen voorafgaand aan de diagnose ziekte van Wegener. Ned Tijdschr Geneeskd. 1987 Aug 8;131(32):1391–1394. [PubMed]
  • Tervaert JW, Goldschmeding R, Elema JD, van der Giessen M, Huitema MG, van der Hem GK, The TH, von dem Borne AE, Kallenberg CG. Autoantibodies against myeloid lysosomal enzymes in crescentic glomerulonephritis. Kidney Int. 1990 Feb;37(2):799–806. [PubMed]
  • Tervaert JW, Goldschmeding R, Elema JD, Limburg PC, van der Giessen M, Huitema MG, Koolen MI, Hené RJ, The TH, van der Hem GK, et al. Association of autoantibodies to myeloperoxidase with different forms of vasculitis. Arthritis Rheum. 1990 Aug;33(8):1264–1272. [PubMed]
  • Tervaert JW, van der Woude FJ, Fauci AS, Ambrus JL, Velosa J, Keane WF, Meijer S, van der Giessen M, van der Hem GK, The TH, et al. Association between active Wegener's granulomatosis and anticytoplasmic antibodies. Arch Intern Med. 1989 Nov;149(11):2461–2465. [PubMed]
  • Conn DL, McDuffie FC, Holley KE, Schroeter AL. Immunologic mechanisms in systemic vasculitis. Mayo Clin Proc. 1976 Aug;51(8):511–518. [PubMed]
  • DeKruyff RH, Turner T, Abrams JS, Palladino MA, Jr, Umetsu DT. Induction of human IgE synthesis by CD4+ T cell clones. Requirement for interleukin 4 and low molecular weight B cell growth factor. J Exp Med. 1989 Nov 1;170(5):1477–1493. [PMC free article] [PubMed]
  • Fagan DL, Slaughter CA, Capra JD, Sullivan TJ. Monoclonal antibodies to immunoglobulin G4 induce histamine release from human basophils in vitro. J Allergy Clin Immunol. 1982 Nov;70(5):399–404. [PubMed]
  • Falk RJ, Jennette JC. Anti-neutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and idiopathic necrotizing and crescentic glomerulonephritis. N Engl J Med. 1988 Jun 23;318(25):1651–1657. [PubMed]
  • Fauci AS, Haynes BF, Katz P, Wolff SM. Wegener's granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med. 1983 Jan;98(1):76–85. [PubMed]
  • Fienberg R. The protracted superficial phenomenon in pathergic (Wegener's) granulomatosis. Hum Pathol. 1981 May;12(5):458–467. [PubMed]
  • Flanagan JG, Rabbitts TH. Arrangement of human immunoglobulin heavy chain constant region genes implies evolutionary duplication of a segment containing gamma, epsilon and alpha genes. Nature. 1982 Dec 23;300(5894):709–713. [PubMed]
  • French MA, Harrison G. Serum IgG subclass concentrations in healthy adults: a study using monoclonal antisera. Clin Exp Immunol. 1984 May;56(2):473–475. [PMC free article] [PubMed]
  • Gilljam G, Wahren B. Properties of IgG subclasses to human cytomegalovirus. J Virol Methods. 1989 Aug;25(2):139–151. [PubMed]
  • Goldschmeding R, van der Schoot CE, ten Bokkel Huinink D, Hack CE, van den Ende ME, Kallenberg CG, von dem Borne AE. Wegener's granulomatosis autoantibodies identify a novel diisopropylfluorophosphate-binding protein in the lysosomes of normal human neutrophils. J Clin Invest. 1989 Nov;84(5):1577–1587. [PMC free article] [PubMed]
  • Grau GE, Roux-Lombard P, Gysler C, Lambert C, Lambert PH, Dayer JM, Guillevin L. Serum cytokine changes in systemic vasculitis. Immunology. 1989 Oct;68(2):196–198. [PMC free article] [PubMed]
  • Hassan NF, Kamani N, Meszaros MM, Douglas SD. Induction of multinucleated giant cell formation from human blood-derived monocytes by phorbol myristate acetate in in vitro culture. J Immunol. 1989 Oct 1;143(7):2179–2184. [PubMed]
  • Heiner DC. Significance of immunoglobulin G subclasses. Am J Med. 1984 Mar 30;76(3A):1–6. [PubMed]
  • Houtman PM, Kallenberg CG, Limburg PC, van Leeuwen MA, van Rijswijk MH, The TH. Fluctuations in anti-nRNP levels in patients with mixed connective tissue disease are related to disease activity as part of a polyclonal B cell response. Ann Rheum Dis. 1986 Oct;45(10):800–808. [PMC free article] [PubMed]
  • Johnson RJ, Couser WG, Chi EY, Adler S, Klebanoff SJ. New mechanism for glomerular injury. Myeloperoxidase-hydrogen peroxide-halide system. J Clin Invest. 1987 May;79(5):1379–1387. [PMC free article] [PubMed]
  • Lee SS, Adu D, Thompson RA. Anti-myeloperoxidase antibodies in systemic vasculitis. Clin Exp Immunol. 1990 Jan;79(1):41–46. [PMC free article] [PubMed]
  • Mancini G, Carbonara AO, Heremans JF. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965 Sep;2(3):235–254. [PubMed]
  • Merrill DP. Purification of human myeloperoxidase by Concanavalin A-Sepharose affinity chromatography. Prep Biochem. 1980;10(2):133–50. [PubMed]
  • Mongini PK, Paul WE, Metcalf ES. T cell regulation of immunoglobulin class expression in the antibody response to trinitrophenyl-ficoll. Evidence for T cell enhancement of the immunoglobulin class switch. J Exp Med. 1982 Mar 1;155(3):884–902. [PMC free article] [PubMed]
  • Parkes AB, McLachlan SM, Bird P, Rees Smith B. The distribution of microsomal and thyroglobulin antibody activity among the IgG subclasses. Clin Exp Immunol. 1984 Jul;57(1):239–243. [PMC free article] [PubMed]
  • Peleman R, Wu J, Fargeas C, Delespesse G. Recombinant interleukin 4 suppresses the production of interferon gamma by human mononuclear cells. J Exp Med. 1989 Nov 1;170(5):1751–1756. [PMC free article] [PubMed]
  • Rock B, Labib RS, Diaz LA. Monovalent Fab' immunoglobulin fragments from endemic pemphigus foliaceus autoantibodies reproduce the human disease in neonatal Balb/c mice. J Clin Invest. 1990 Jan;85(1):296–299. [PMC free article] [PubMed]
  • Rock B, Martins CR, Theofilopoulos AN, Balderas RS, Anhalt GJ, Labib RS, Futamura S, Rivitti EA, Diaz LA. The pathogenic effect of IgG4 autoantibodies in endemic pemphigus foliaceus (fogo selvagem). N Engl J Med. 1989 Jun 1;320(22):1463–1469. [PubMed]
  • Rubin RL, Tang FL, Chan EK, Pollard KM, Tsay G, Tan EM. IgG subclasses of autoantibodies in systemic lupus erythematosus, Sjogren's syndrome, and drug-induced autoimmunity. J Immunol. 1986 Oct 15;137(8):2528–2534. [PubMed]
  • Savage CO, Winearls CG, Jones S, Marshall PD, Lockwood CM. Prospective study of radioimmunoassay for antibodies against neutrophil cytoplasm in diagnosis of systemic vasculitis. Lancet. 1987 Jun 20;1(8547):1389–1393. [PubMed]
  • Schur PH. IgG subclasses--a review. Ann Allergy. 1987 Feb;58(2):89–99. [PubMed]
  • Shakib F. Aspects of the pathological significance of IgG4. Exp Clin Immunogenet. 1987;4(4):193–200. [PubMed]
  • Shapiro SS, Carroll KS. Acquired factor 8 antibodies: further immunologic and electrophoretic studies. Science. 1968 May 17;160(3829):786–787. [PubMed]
  • Spiegelberg HL. Biological role of different antibody classes. Int Arch Allergy Appl Immunol. 1989;90 (Suppl 1):22–27. [PubMed]
  • Van der Giessen M, van den Berg AP, van der Bij W, Postma S, van Son WJ, The TH. Quantitative measurement of cytomegalovirus-specific IgG and IgM antibodies in relation to cytomegalovirus antigenaemia and disease activity in kidney recipients with an active cytomegalovirus infection. Clin Exp Immunol. 1990 Apr;80(1):56–61. [PMC free article] [PubMed]
  • van der Giessen M, Homan WL, van Kernbeek G, Aalberse RC, Dieges PH. Subclass typing of IgG antibodies formed by grass pollen-allergic patients during immunotherapy. Int Arch Allergy Appl Immunol. 1976;50(5):625–640. [PubMed]
  • van der Giessen M, Rossouw E, van Veen TA, van Loghem E, Zegers BJ, Sander PC. Quantification of IgG subclasses in sera of normal adults and healthy children between 4 and 12 years of age. Clin Exp Immunol. 1975 Sep;21(3):501–509. [PMC free article] [PubMed]
  • van der Woude FJ, Rasmussen N, Lobatto S, Wiik A, Permin H, van Es LA, van der Giessen M, van der Hem GK, The TH. Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener's granulomatosis. Lancet. 1985 Feb 23;1(8426):425–429. [PubMed]
  • van der Zee JS, van Swieten P, Aalberse RC. Serologic aspects of IgG4 antibodies. II. IgG4 antibodies form small, nonprecipitating immune complexes due to functional monovalency. J Immunol. 1986 Dec 1;137(11):3566–3571. [PubMed]

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