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Are anti-C1q antibodies different from other SLE autoantibodies?

Nature Reviews Rheumatology volume 6, pages 490–493 (2010)Cite this article

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Abstract

Anti-C1q antibodies were first identified as low-molecular weight C1q precipitins in the sera of patients with systemic lupus erythematosus (SLE) over 30 years ago. Anti-C1q antibodies are strongly associated with the development of proliferative lupus nephritis, so much so that active renal inflammation in SLE patients is very unlikely if these antibodies are not present. These antibodies seem to develop through mechanisms that are similar to those of other SLE autoantibodies.

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Figure 1: Detection of anti-C1q antibodies.
Figure 2: Generation of anti-C1q antibodies.
Figure 3: Renal inflammation and anti-C1q antibodies.

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References

  1. Sellar, G. C., Blake, D. J. & Reid, K. B. Characterization and organization of the genes encoding the A-, B- and C-chains of human complement subcomponent C1q. The complete derived amino acid sequence of human C1q. Biochem. J. 274 (Pt 2), 481–490 (1991).

    Article  CAS  Google Scholar 

  2. Sim, R. B. & Reid, K. B. C1: molecular interactions with activating systems. Immunol. Today 12, 307–311 (1991).

    Article  CAS  Google Scholar 

  3. Cooper, N. R. The classical complement pathway: activation and regulation of the first complement component. Adv. Immunol. 37, 151–216 (1985).

    Article  CAS  Google Scholar 

  4. Feinstein, A., Richardson, N. & Taussig, M. J. Immunoglobulin flexibility in complement activation. Immunol. Today 7, 169–174 (1986).

    Article  CAS  Google Scholar 

  5. Agnello, V., Koffler, D., Eisenberg, J. W., Winchester, R. J. & Kundel, H. G. C1g precipitins in the sera of patients with systemic lupus erythematosus and other hypocomplementemic states: characterization of high and low molecular weight types. J. Exp. Med. 134, 228–241 (1971).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Antes, U., Heinz, H. P. & Loos, M. Evidence for the presence of autoantibodies to the collagen-like portion of C1q in systemic lupus erythematosus. Arthritis Rheum. 31, 457–464 (1988).

    Article  CAS  Google Scholar 

  7. Schaller, M., Bigler, C., Danner, D., Ditzel, H. J. & Trendelenburg, M. Autoantibodies against C1q in systemic lupus erythematosus are antigen-driven. J. Immunol. 183, 8225–8231 (2009).

    Article  CAS  Google Scholar 

  8. Pickering, M. C., Botto, M., Taylor, P. R., Lachmann, P. J. & Walport, M. J. Systemic lupus erythematosus, complement deficiency, and apoptosis. Adv. Immunol. 76, 227–324 (2000).

    Article  CAS  Google Scholar 

  9. Casciola-Rosen, L. A., Anhalt, G. & Rosen, A. Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J. Exp. Med. 179, 1317–1330 (1994).

    Article  CAS  Google Scholar 

  10. Korb, L. C. & Ahearn, J. M. C1q binds directly and specifically to surface blebs of apoptotic human keratinocytes: complement deficiency and systemic lupus erythematosus revisited. J. Immunol. 158, 4525–4528 (1997).

    CAS  PubMed  Google Scholar 

  11. Bigler, C., Schaller, M., Perahud, I., Osthoff, M. & Trendelenburg, M. Autoantibodies against complement C1q specifically target C1q bound on early apoptotic cells. J. Immunol. 183, 3512–3521 (2009).

    Article  CAS  Google Scholar 

  12. Hunnangkul, S. et al. Familial clustering of non-nuclear autoantibodies and C3 and C4 complement components in systemic lupus erythematosus. Arthritis Rheum. 58, 1116–1124 (2008).

    Article  Google Scholar 

  13. Trendelenburg, M. Antibodies against C1q in patients with systemic lupus erythematosus. Springer Semin. Immunopathol. 27, 276–285 (2005).

    Article  CAS  Google Scholar 

  14. Kallenberg, C. G. Anti-C1q autoantibodies. Autoimmun. Rev. 7, 612–615 (2008).

    Article  CAS  Google Scholar 

  15. Siegert, C. E., Daha, M. R., Halma, C., van der Voort, E. A. & Breedveld, F. C. IgG and IgA autoantibodies to C1q in systemic and renal diseases. Clin. Exp. Rheumatol. 10, 19–23 (1992).

    CAS  PubMed  Google Scholar 

  16. Wisnieski, J. J. & Naff, G. B. Serum IgG antibodies to C1q in hypocomplementemic urticarial vasculitis syndrome. Arthritis Rheum. 32, 1119–1127 (1989).

    Article  CAS  Google Scholar 

  17. Prada, A. E. & Strife, C. F. IgG subclass restriction of autoantibody to solid-phase C1q in membranoproliferative and lupus glomerulonephritis. Clin. Immunol. Immunopathol. 63, 84–88 (1992).

    Article  CAS  Google Scholar 

  18. Trendelenburg, M. et al. High prevalence of anti-C1q antibodies in biopsy-proven active lupus nephritis. Nephrol. Dial. Transplant 21, 3115–3121 (2006).

    Article  CAS  Google Scholar 

  19. Trendelenburg, M., Marfurt, J., Gerber, I., Tyndall, A. & Schifferli, J. A. Lack of occurrence of severe lupus nephritis among anti-C1q autoantibody-negative patients. Arthritis Rheum. 42, 187–188 (1999).

    Article  CAS  Google Scholar 

  20. Siegert, C., Daha, M., Westedt, M. L., van der Voort, E. & Breedveld, F. IgG autoantibodies against C1q are correlated with nephritis, hypocomplementemia, and dsDNA antibodies in systemic lupus erythematosus. J. Rheumatol. 18, 230–234 (1991).

    CAS  PubMed  Google Scholar 

  21. Coremans, I. E. et al. Changes in antibodies to C1q predict renal relapses in systemic lupus erythematosus. Am. J. Kidney Dis. 26, 595–601 (1995).

    Article  CAS  Google Scholar 

  22. Moroni, G. et al. Anti-C1q antibodies may help in diagnosing a renal flare in lupus nephritis. Am. J. Kidney Dis. 37, 490–498 (2001).

    Article  CAS  Google Scholar 

  23. Siegert, C. E. et al. Predictive value of IgG autoantibodies against C1q for nephritis in systemic lupus erythematosus. Ann. Rheum. Dis. 52, 851–856 (1993).

    Article  CAS  Google Scholar 

  24. Sinico, R. A. et al. Anti-C1q autoantibodies in lupus nephritis. Ann. NY Acad. Sci. 1173, 47–51 (2009).

    Article  CAS  Google Scholar 

  25. Mannik, M. & Wener, M. H. Deposition of antibodies to the collagen-like region of C1q in renal glomeruli of patients with proliferative lupus glomerulonephritis. Arthritis Rheum. 40, 1504–1511 (1997).

    Article  CAS  Google Scholar 

  26. Mannik, M., Merrill, C. E., Stamps, L. D. & Wener, M. H. Multiple autoantibodies form the glomerular immune deposits in patients with systemic lupus erythematosus. J. Rheumatol. 30, 1495–1504 (2003).

    PubMed  Google Scholar 

  27. Trouw, L. A. et al. Anti-C1q autoantibodies deposit in glomeruli but are only pathogenic in combination with glomerular C1q-containing immune complexes. J. Clin. Invest. 114, 679–688 (2004).

    Article  CAS  Google Scholar 

  28. Holers, V. M. Anti-C1q autoantibodies amplify pathogenic complement activation in systemic lupus erythematosus. J. Clin. Invest. 114, 616–619 (2004).

    Article  CAS  Google Scholar 

  29. Flierman, R. & Daha, M. R. Pathogenic role of anti-C1q autoantibodies in the development of lupus nephritis—a hypothesis. Mol. Immunol. 44, 133–138 (2007).

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to acknowledge The Wellcome Trust, which funds the research of M. Botto and M. C. Pickering.

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  1. Department of Medicine, Rheumatology Section, Faculty of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, W12 ONN, London, UK

    Matthew C. Pickering & Marina Botto

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Correspondence to Marina Botto.

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The authors declare no competing financial interests.

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Pickering, M., Botto, M. Are anti-C1q antibodies different from other SLE autoantibodies?. Nat Rev Rheumatol 6, 490–493 (2010). https://doi.org/10.1038/nrrheum.2010.56

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