Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1991 Dec;74(4):714–718.

IgG subclass distribution and relative functional affinity of anti-myeloperoxidase antibodies in systemic vasculitis at presentation and during follow-up.

V L Esnault 1, D R Jayne 1, A P Weetman 1, C M Lockwood 1
PMCID: PMC1384785  PMID: 1664417

Abstract

Circulating IgG autoantibodies to myeloperoxidase (MPO) are associated with renal vasculitis and have been implicated in its pathogenesis. However, raised levels of these autoantibodies may persist during clinical remission. We tested whether this paradox could be explained by immunoglobulin subclass switching during disease evolution, since different subclasses have different immunological and biochemical properties. Sera with anti-myeloperoxidase (anti-MPO) activity from 33 patients with active disease and 20 anti-MPO positive follow-up sera were studied by an ELISA using a panel of anti-human IgG subclass monoclonal reagents previously calibrated on human myeloma proteins. Anti-MPO subclass distribution in initial sera was: IgG1, 31 (94%); IgG2, 10 (30%); IgG3, 24 (73%); and IgG4, 22 (67%). IgG3 anti-MPO decreased during follow-up (P less than 0.02), with no change in IgG1 and IgG4. Relative functional affinity of anti-MPO antibodies in purified IgG subclasses was studied by the diethylamine method. IgG3 fractions consistently had a greater affinity for MPO than the other subclasses. Sequential studies in four patients demonstrated an affinity maturation for IgG1 and IgG4 anti-MPO as IgG3 anti-MPO disappeared. We conclude that dynamic changes of subclass distribution and affinity may explain discrepancies between anti-MPO antibody titre and disease expression.

Full text

PDF
714

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aalberse R. C., 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] [Google Scholar]
  2. Almond N. M., Parkhouse R. M. The Ig class distribution of anti-phosphoryl choline responses in mice infected with parasitic nematodes. Immunology. 1986 Dec;59(4):633–635. [PMC free article] [PubMed] [Google Scholar]
  3. Black C. M., Plikaytis B. D., Wells T. W., Ramirez R. M., Carlone G. M., Chilmonczyk B. A., Reimer C. B. Two-site immunoenzymometric assays for serum IgG subclass infant/maternal ratios at full-term. J Immunol Methods. 1988 Jan 21;106(1):71–81. doi: 10.1016/0022-1759(88)90273-6. [DOI] [PubMed] [Google Scholar]
  4. Bowman C., Ambrus K., Lockwood C. M. 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] [Google Scholar]
  5. Brouwer E., Tervaert J. W., Horst G., Huitema M. G., van der Giessen M., Limburg P. C., Kallenberg C. G. Predominance of IgG1 and IgG4 subclasses of anti-neutrophil cytoplasmic autoantibodies (ANCA) in patients with Wegener's granulomatosis and clinically related disorders. Clin Exp Immunol. 1991 Mar;83(3):379–386. doi: 10.1111/j.1365-2249.1991.tb05647.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Burton D. R. Immunoglobulin G: functional sites. Mol Immunol. 1985 Mar;22(3):161–206. doi: 10.1016/0161-5890(85)90151-8. [DOI] [PubMed] [Google Scholar]
  7. Devey M. E., Bleasdale K., Lee S., Rath S. Determination of the functional affinity of IgG1 and IgG4 antibodies to tetanus toxoid by isotype-specific solid-phase assays. J Immunol Methods. 1988 Jan 21;106(1):119–125. doi: 10.1016/0022-1759(88)90279-7. [DOI] [PubMed] [Google Scholar]
  8. Devey M. E., Lee S. R., Le Page S., Feldman R., Isenberg D. A. Serial studies of the IgG subclass and functional affinity of DNA antibodies in systemic lupus erythematosus. J Autoimmun. 1988 Oct;1(5):483–494. doi: 10.1016/0896-8411(88)90069-8. [DOI] [PubMed] [Google Scholar]
  9. Falk R. J., Jennette J. C. 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. doi: 10.1056/NEJM198806233182504. [DOI] [PubMed] [Google Scholar]
  10. Falk R. J., Terrell R. S., Charles L. A., Jennette J. C. Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4115–4119. doi: 10.1073/pnas.87.11.4115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fellows G., Gittoes N., Scott D. G., Coppock J. S., Wainwright A., Goodall M., Turner B. M. Individual variation in the isotype profile of anti-histone autoantibodies in systemic lupus erythematosus. Clin Exp Immunol. 1988 Jun;72(3):440–445. [PMC free article] [PubMed] [Google Scholar]
  12. Goldschmeding R., van der Schoot C. E., ten Bokkel Huinink D., Hack C. E., van den Ende M. E., Kallenberg C. G., von dem Borne A. E. 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. doi: 10.1172/JCI114335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Grau G. E., Roux-Lombard P., Gysler C., Lambert C., Lambert P. H., Dayer J. M., Guillevin L. Serum cytokine changes in systemic vasculitis. Immunology. 1989 Oct;68(2):196–198. [PMC free article] [PubMed] [Google Scholar]
  14. Jansson R., Thompson P. M., Clark F., McLachlan S. M. Association between thyroid microsomal antibodies of subclass IgG-1 and hypothyroidism in autoimmune postpartum thyroiditis. Clin Exp Immunol. 1986 Jan;63(1):80–86. [PMC free article] [PubMed] [Google Scholar]
  15. Jayne D. R., Weetman A. P., Lockwood C. M. IgG subclass distribution of autoantibodies to neutrophil cytoplasmic antigens in systemic vasculitis. Clin Exp Immunol. 1991 Jun;84(3):476–481. [PMC free article] [PubMed] [Google Scholar]
  16. Klasse P. J., Berntorp E., Hansson B. G. An aberrant subclass pattern of HIV-specific immunoglobulin G in sera from haemophiliacs. AIDS. 1988 Aug;2(4):311–313. [PubMed] [Google Scholar]
  17. Lüdemann G., Gross W. L. Autoantibodies against cytoplasmic structures of neutrophil granulocytes in Wegener's granulomatosis. Clin Exp Immunol. 1987 Aug;69(2):350–357. [PMC free article] [PubMed] [Google Scholar]
  18. Lüdemann J., Utecht B., Gross W. L. Anti-neutrophil cytoplasm antibodies in Wegener's granulomatosis recognize an elastinolytic enzyme. J Exp Med. 1990 Jan 1;171(1):357–362. doi: 10.1084/jem.171.1.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Michaelsen T. E., Garred P., Aase A. Human IgG subclass pattern of inducing complement-mediated cytolysis depends on antigen concentration and to a lesser extent on epitope patchiness, antibody affinity and complement concentration. Eur J Immunol. 1991 Jan;21(1):11–16. doi: 10.1002/eji.1830210103. [DOI] [PubMed] [Google Scholar]
  20. Niles J. L., McCluskey R. T., Ahmad M. F., Arnaout M. A. Wegener's granulomatosis autoantigen is a novel neutrophil serine proteinase. Blood. 1989 Nov 1;74(6):1888–1893. [PubMed] [Google Scholar]
  21. Noël L. H., Aucouturier P., Monteiro R. C., Preud'Homme J. L., Lesavre P. Glomerular and serum immunoglobulin G subclasses in membranous nephropathy and anti-glomerular basement membrane nephritis. Clin Immunol Immunopathol. 1988 Feb;46(2):186–194. doi: 10.1016/0090-1229(88)90181-x. [DOI] [PubMed] [Google Scholar]
  22. Nölle B., Specks U., Lüdemann J., Rohrbach M. S., DeRemee R. A., Gross W. L. Anticytoplasmic autoantibodies: their immunodiagnostic value in Wegener granulomatosis. Ann Intern Med. 1989 Jul 1;111(1):28–40. doi: 10.7326/0003-4819-111-1-28. [DOI] [PubMed] [Google Scholar]
  23. Parkes A. B., McLachlan S. M., 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] [Google Scholar]
  24. Reimer C. B., Phillips D. J., Aloisio C. H., Moore D. D., Galland G. G., Wells T. W., Black C. M., McDougal J. S. Evaluation of thirty-one mouse monoclonal antibodies to human IgG epitopes. Hybridoma. 1984 Fall;3(3):263–275. doi: 10.1089/hyb.1984.3.263. [DOI] [PubMed] [Google Scholar]
  25. Savage C. O., Winearls C. G., Jones S., Marshall P. D., Lockwood C. M. Prospective study of radioimmunoassay for antibodies against neutrophil cytoplasm in diagnosis of systemic vasculitis. Lancet. 1987 Jun 20;1(8547):1389–1393. doi: 10.1016/s0140-6736(87)90591-5. [DOI] [PubMed] [Google Scholar]
  26. Slack J. H. Strain-dependent IgG subclass response patterns. J Immunol. 1987 Dec 1;139(11):3734–3738. [PubMed] [Google Scholar]
  27. Snapper C. M., Peschel C., Paul W. E. IFN-gamma stimulates IgG2a secretion by murine B cells stimulated with bacterial lipopolysaccharide. J Immunol. 1988 Apr 1;140(7):2121–2127. [PubMed] [Google Scholar]
  28. Stevens T. L., Bossie A., Sanders V. M., Fernandez-Botran R., Coffman R. L., Mosmann T. R., Vitetta E. S. Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells. Nature. 1988 Jul 21;334(6179):255–258. doi: 10.1038/334255a0. [DOI] [PubMed] [Google Scholar]
  29. Taaning E., Scheibel E., Laursen B., Ingerslev J. Pattern of immunoglobulin classes and IgG subclasses of platelet-associated immunoglobulin in HIV-seropositive haemophiliacs. Vox Sang. 1988;54(4):205–209. doi: 10.1111/j.1423-0410.1988.tb03906.x. [DOI] [PubMed] [Google Scholar]
  30. Tervaert J. W., van der Woude F. J., Fauci A. S., Ambrus J. L., Velosa J., Keane W. F., Meijer S., van der Giessen M., van der Hem G. K., The T. H. Association between active Wegener's granulomatosis and anticytoplasmic antibodies. Arch Intern Med. 1989 Nov;149(11):2461–2465. doi: 10.1001/archinte.149.11.2461. [DOI] [PubMed] [Google Scholar]
  31. Thompson P. M., McLachlan S. M., Parkes A., Clark F., Howel D., Rees Smith B. The IgG subclass distribution of thyroglobulin antibody synthesized in culture. Scand J Immunol. 1983 Aug;18(2):123–129. doi: 10.1111/j.1365-3083.1983.tb00848.x. [DOI] [PubMed] [Google Scholar]
  32. Weetman A. P., Black C. M., Cohen S. B., Tomlinson R., Banga J. P., Reimer C. B. Affinity purification of IgG subclasses and the distribution of thyroid auto-antibody reactivity in Hashimoto's thyroiditis. Scand J Immunol. 1989 Jul;30(1):73–82. doi: 10.1111/j.1365-3083.1989.tb01190.x. [DOI] [PubMed] [Google Scholar]
  33. Winkler T. H., Henschel T. A., Kalies I., Baenkler H. W., Skvaril F., Kalden J. R. Constant isotype pattern of anti-dsDNA antibodies in patients with systemic lupus erythematosus. Clin Exp Immunol. 1988 Jun;72(3):434–439. [PMC free article] [PubMed] [Google Scholar]
  34. van der Woude F. J., Rasmussen N., Lobatto S., Wiik A., Permin H., van Es L. A., van der Giessen M., van der Hem G. K., The T. H. 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. doi: 10.1016/s0140-6736(85)91147-x. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES