Autoreactivity to mouse C1q in a murine model of SLE (original) (raw)

Abstract

A large proportion of systemic lupus erythematosus (SLE) patients develop glomerulonephritis, coincident with the appearance of autoantibodies to C1q, the Fcrecognizing collagen-like subcomponent of the first component of complement, C1. The MRL/lpr/lpr mouse is an established model for SLE, developing both antinuclear and anti-type II collagen autoantibodies, and rheumatoid factors(s), exhibiting reduced complement levels and later on developing glomerulonephritis and often arthritis. We report here an age-dependent decrease in serum C1q levels coincident with the development of IgG2b autoantibodies reactive with mouse C1q in MRL/lpr/lpr mice. Unlike IgG2b, although high levels of IgM, IgG1 and IgG2a are present in these mice, few, if any, antibodies of these sub-classes reactive with mouse C1q were observed in this study. This is the first report of autoantibodies against autologous C1q in an animal model, and the results should facilitate in clarification of the roles of C1q and autoantibodies reactive with C1q in SLE, as well as their potential connection with glomerulonephritis.

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References

  1. Theofilopoulos AN, Dixon FJ (1985) Murine models of systemic lupus erythematosus. Adv Immunol 37:269–390
    Google Scholar
  2. Andrews BS, Eisenberg RS, Theofilopoulos AN, Izui S, Wilson CB, McConahey PJ, Murphy ED, Roths JB, Doxon EJ (1978) Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med 148:1198–1215
    Google Scholar
  3. Parekh RB, Dwek RA, Sutton BJ, Fernandes DL, Leung A, Staworth D, Rademacher TW, Mizuochi T, Tanigushi K, Matsuta K, Takeuchi Y, Nagano T, Miyamoto T, Kobata A (1985) Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG. Nature 310:452–457
    Google Scholar
  4. Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, Doménech I, Aydintug AO, Jedryka-Góral A, de Ramon E, Galeazzi M, Haga H-J, Mathieu A, Houssiau F, Ingelmo M, Hughes GRV, the European Working Party on Systemic Lupus Erythematosus (1993) Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. Medicine 72: 113–124
    Google Scholar
  5. Steinberg AD (1994) MRL-lpr/lpŕ disease: theories meet Fas. Semin Immunol 6:55–69
    Google Scholar
  6. Abrass CK, Niess KM, Louie JS, Border WA, Glassock RJ (1980) Correlation and predictive accuracy of circulating immune complexes with disease activity in patients with systemic lupus erythematosus. Arthritis Rheum 23:273–282
    Google Scholar
  7. Antes U, Heinz H-P, Loos M (1987) Detection of C1q-bearing immune complexes by a monoclonal anti-C1q ELISA system. J Immunol Methods 102:149–156
    Google Scholar
  8. Antes U, Heinz H-P, Loos M (1988) Evidence for the presence of autoantibodies to the collagen-like portion of C1q in systemic lupus erythematosus. Arthritis Rheum 31:457–464
    Google Scholar
  9. Siegert CEH, Breedfeld FC, Daha MR (1993) Autoantibodies against C1q in systemic lupus erythematosus. Behring Inst Mitt 93:279–286
    Google Scholar
  10. Stemmer F, Loos M (1984) Purification and characterization of human, guinea pig and mouse C1q by fast protein liquid chromatography (FPLC). J Immunol Methods 74:9–16
    Google Scholar
  11. Schorlemmer HU, Bartlett RR, Seiler FR (1991) Curative effects of 15-deoxyspergualin on murine systemic lupus erythematosus-like disease in MRL/l autoimmune mice. Int J Immunother 7:169–180
    Google Scholar
  12. Shan H, Shlomchik MJ, Marshak-Rothstein A, Pisetsky DS, Litwin S, Weigert MG (1994) The mechanism of autoantibody production in an autoimmune MRL/lpr mouse. J Immunol 153:5104–5120
    Google Scholar
  13. Prada AE, Strife CF (1992) IgG subclass restriction of autoantibody to solid-phase C1q in membranoproliferative and lupus glomerulonephritis. Clin Immunol Immunopathol 63:84–88
    Google Scholar
  14. Slack JH, Hang L-M, Barkley J, Fulton RJ, D'Hoostelaere LD, Robinson A, Dixon FJ (1984) Isotypes of spontaneous and mitogen-induced autoantibodies in SLE-prone mice. J Immunol 132:1217–1275
    Google Scholar
  15. Petry F, Reid KBM, Loos M (1991) Gene expression the A-and B-chain of mouse C1q in different tissues and the characterization of the recombinant A-chain. J Immunol 147:3988–3993
    Google Scholar
  16. Colten HR, Strunk RC (1993) Synthesis of complement components in liver and at extrahepatic sites. In: Whaley K, Loos M, Weiler JM (eds) Complement in health and disease, 2nd edn. Kluwer, Lancester, UK, pp 127–158
    Google Scholar
  17. Phadke K, Fouts R, Parrish J, Baker RS (1984) Autoreactivity to collagen in a murine lupus model. Arthritis Rheum 27:313–319
    Google Scholar
  18. Cook AD, Rowley MJ, Wines BD, Mackay IR (1994) Antibodies to the collagen-like region of C1q and type II collagen are independent non-cross-reactive populations in systemic lupus erythematosus and rheumatoid arthritis. J Autoimmun 7:369–378
    Google Scholar

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Authors and Affiliations

  1. Institute of Medical Microbiology and Hygiene, Johannes Gutenberg University, Hochhaus/Augustusplatz, D-55101, Mainz, Germany
    P. K. E. Trinder & M. Loos
  2. Department of Surgery, University of Pittsburgh Medical School, Pittsburgh, PA, USA
    M. J. Maeurer
  3. Department of Biochemistry, University of Pittsburgh Medical School, Pittsburgh, PA, USA
    M. J. Maeurer
  4. Department of Molecular Genetics, University of Pittsburgh Medical School, Pittsburgh, PA, USA
    M. J. Maeurer
  5. Pharma Research Laboratories, Behringwerke AG, Marburg, Germany
    H. -U. Schorlemmer

Authors

  1. P. K. E. Trinder
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  2. M. J. Maeurer
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  3. H. -U. Schorlemmer
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  4. M. Loos
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Trinder, P.K.E., Maeurer, M.J., Schorlemmer, H.U. et al. Autoreactivity to mouse C1q in a murine model of SLE.Rheumatol Int 15, 117–120 (1995). https://doi.org/10.1007/BF00302128

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