Skip to main content

Advertisement

SpringerLink
Log in

Nonrenal and renal activity of systemic lupus erythematosus: a comparison of two anti-C1q and five anti-dsDNA assays and complement C3 and C4

  • Original Article
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

Associations of different assays for antibodies to C1q (anti-C1q) and to dsDNA (anti-dsDNA) and of complements C3 and C4 with disease activity in patients with systemic lupus erythematosus (SLE) were studied. The clinical manifestations of 223 SLE patients were recorded, and the disease activity was assessed by the SLEDAI score. Anti-C1q were determined by two enzyme-linked immunosorbent assays (ELISA) and anti-dsDNA by a radioimmunoassay (RIA), a Crithidia immunofluorescence (IF) assay and three ELISA assays using human telomere DNA, plasmid DNA circles, or calf thymus DNA as antigens, respectively. Complement C3 and C4 were determined by nephelometry. Control sera were obtained from 98 blood donors. In patients with SLE, the prevalence of anti-C1q was 17–18% and that of anti-dsDNA was 36–69%. Anti-C1q, anti-dsDNA, and complement C3 and C4 correlated well with the overall activity of SLE (r = 0.323–0.351, 0.353–0.566, and −0.372–0.444, respectively; P < 0.001). Sensitivity, specificity, positive predictive value, and negative predictive value for active lupus nephritis among SLE patients were 40–44, 92, 29, and 91–92% for anti-C1q and 48–68, 29–66, 11–16, and 86–91% for anti-dsDNA, respectively. Patients with active nephritis had higher levels of anti-C1q and lower levels of C3 and C4 than patients with inactive nephritis (P = 0.003–0.018). The corresponding associations of anti-dsDNA were somewhat weaker (P = 0.023–0.198). Hematological parameters reflecting disease activity correlated clearly better with anti-dsDNA and complement C3 and C4 than with anti-C1q. Anti-C1q is inferior to anti-dsDNA as a diagnostic test in SLE and in the evaluation of overall clinical activity of the disease. Anti-C1q together with complement C3 and C4 may offer useful additional information to monitor lupus nephritis activity. There are no practical differences between different assays for anti-C1q and anti-dsDNA.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Isenberg DA, Ravirajan CT, Rahman A, Kalsi J (1997) The role of antibodies to DNA in systemic lupus erythematosus—a review and introduction to an international workshop on DNA antibodies held in London, May 1996. Lupus 6:290–304

    Article  PubMed  CAS  Google Scholar 

  2. Lloyd W, Schur PH (1981) Immune complexes, complement, and anti-DNA in exacerbations of systemic lupus erythematosus. Medicine 60:208–217

    Article  PubMed  CAS  Google Scholar 

  3. Hahn B (1998) Antibodies to DNA. N Engl J Med 338:1359–1368

    Article  PubMed  CAS  Google Scholar 

  4. Esdaile JM, Abrahamowicz M, Joseph L et al (1996) Laboratory tests as predictors of disease exacerbations in systemic lupus erythematosus: why some tests fail. Arthritis Rheum 39:370–378

    Article  PubMed  CAS  Google Scholar 

  5. Sawalha AH, Harley JB (2004) Antinuclear autoantibodies in systemic lupus erythematosus. Curr Opin Rheumatol 16:534–540

    Article  PubMed  Google Scholar 

  6. Illei GG, Tackey E, Lapteva L et al (2004) Biomarkers for systemic lupus erythematosus. II. Markers of disease activity. Arthritis Rheum 50:2048–2065

    Article  PubMed  CAS  Google Scholar 

  7. Liu C-C, Manzi S, Ahearn JM (2005) Biomarkers for systemic lupus erythematosus: a review and perspective. Curr Opin Rheumatol 17:543–549

    Article  PubMed  CAS  Google Scholar 

  8. Werle E, Blazek M, Fiehn W (1992) The clinical significance of measuring different anti-dsDNA antibodies by using the Farr assay, an enzyme immunoassay and a Crithidia luciliae immunofluorescence test. Lupus 1:369–377

    Article  PubMed  CAS  Google Scholar 

  9. James K, Meek G (1992) Evaluation of commercial enzyme immunoassays compared to immunofluorescence and double diffusion for autoantibodies associated with auto-immune diseases. Am J Clin Pathol 97:559–565

    PubMed  CAS  Google Scholar 

  10. Salonen EM, Miettinen A, Walle T, Koskenmies S, Kere J, Julkunen H (2004) Anti-telomere antibodies in systemic lupus erythematosus (SLE): a comparison with five antinuclear antibody assays in 430 patients with SLE and other rheumatic diseases. Ann Rheum Dis 63:1250–1254

    Article  PubMed  CAS  Google Scholar 

  11. Schiffenbauer J, Hahn B, Weisman MH et al (2004) Biomarkers, surrogate markers, and design of clinical trials of new therapies for systemic lupus erythematosus. Arthritis Rheum 50:2415–2422

    Article  PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  13. Siegert CE, Daha MR, Halma C, van der Voort EA, Breedveld FC (1992) IgG and IgA autoantibodies to C1q in systemic and renal diseases. Clin Exp Rheumatol 10:19–23

    PubMed  CAS  Google Scholar 

  14. Wisnieski JJ, Jones SM (1992) IgG autoantibody to the collagen-like region of Clq in hypocomplementemic urticarial vasculitis syndrome, systemic lupus erythematosus, and 6 other musculoskeletal or rheumatic diseases. J Rheumatol 19:884–888

    PubMed  CAS  Google Scholar 

  15. Gunnarsson I, Ronnelid J, Huang YH et al (1997) Association between ongoing anti-C1q antibody production in peripheral blood and proliferative nephritis in patients with active systemic lupus erythematosus. Br J Rheumatol 36:32–37

    Article  PubMed  CAS  Google Scholar 

  16. Siegert CE, Daha MR, Tseng CM, Coremans IE, van Es LA, Breedveld FC (1993) Predictive value of IgG autoantibodies against C1q for nephritis in systemic lupus erythematosus. Ann Rheum Dis 52:851–856

    Article  PubMed  CAS  Google Scholar 

  17. Oelzner P, Deliyska B, Funfstuck R, Hein G, Herrman D, Stein G (2003) Anti-C1q antibodies and antiendothelial cell antibodies in systemic lupus erythematosus–relationship with disease activity and renal involvement. Clin Rheumatol 22:271–278

    Article  PubMed  CAS  Google Scholar 

  18. Armstrong DJ, Crockard AD, Whitehead EM, Bell AL (2005) Anti-C1q antibodies in renal and nonrenal SLE. Ann Rheum Dis 64:1108

    Article  PubMed  CAS  Google Scholar 

  19. Trendelenburg M, Lopez-Trascasa EP, Potlukova E et al (2006) High prevalence of anti-C1q in biopsy-proven active lupus nephritis. Nephrol Dial Transplant 21:3115–3121

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  21. Fremeaux-Bacchi V, Noel LH, Schifferli JA (2002) No lupus nephritis in the absence of anti-C1q autoantibodies ? Nephrol Dial Transplant 17:2041–2043

    Article  PubMed  CAS  Google Scholar 

  22. Siegert CE, Kazatchkine MD, Sjoholm A, Wurzner R, Loos M, Daha MR (1999) Autoantibodies against C1q: view on clinical relevance and pathogenetic role. Clin Exp Immunol 116:4–8

    Article  PubMed  CAS  Google Scholar 

  23. Marto N, Bertolaccini ML, Calabuig E, Hughes GRV, Khamastha MA (2005) Anti-C1q antibodies in nephritis: correlation between titres and renal disease activity and positive predictive value in systemic lupus erythematosus. Ann Rheum Dis 64:444–448

    Article  PubMed  CAS  Google Scholar 

  24. Coremans IE, Spronk PE, Bootsma H et al (1995) Changes in antibodies to C1q predict renal relapses in systemic lupus erythematosus. Am J Kidney Dis 26:595–601

    Article  PubMed  CAS  Google Scholar 

  25. Moroni G, Trendelenburg M, Del Papa N et al (2001) Anti-C1q antibodies may help in diagnosing a renal flare in lupus nephritis. Am J Kidney Dis 37:490–498

    Article  PubMed  CAS  Google Scholar 

  26. Tan EM, Cohen AS, Fries JF et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277

    Article  PubMed  CAS  Google Scholar 

  27. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH, The Committee on Prognosis Studies in SLE (1992) Derivation of the SLEDAI: a disease activity index for lupus patients. Arthritis Rheum 35:630–640

    Article  PubMed  CAS  Google Scholar 

  28. Sheldon J (2004) Laboratory testing in autoimmune rheumatic diseases. Best Pract Res Clin Rheum 18:249–269

    CAS  Google Scholar 

  29. Gunnarsson I, Sundelin B, Heimburger M et al (2002) Repeated renal biopsy in proliferative lupus nephritis—predictive role of serum C1q and albuminuria. J Rheumatol 29:698–699

    Google Scholar 

  30. Walport MJ (2001) Complement. Part 1. N Engl J Med 344:1058–1066

    Article  PubMed  CAS  Google Scholar 

  31. Walport MJ (2001) Complement. Part 2. N Engl J Med 344:1140–1144

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  33. Botto M, Walport MJ (2002) C1q, autoimmunity and apoptosis. Immunobiol 205:395–406

    Article  CAS  Google Scholar 

  34. Bowness P, Davies KA, Norsworthy PJ et al (1994) Hereditary C1q deficiency and systemic lupus erythematosus. Q J Med 87:455–464

    CAS  Google Scholar 

  35. Pickering MC, Botto M, Taylor PR, Lachmann PJ, Walport MJ (2002) Systemic lupus erythematosus, complement deficiency, and apoptosis. Adv Immunol 76:227–234

    Article  Google Scholar 

  36. Trouw LA, Groeneveld TW, Seelen MA et al (2004) Anti-C1q autoantibodies deposit in glomeruli but are only pathogenic in combination with glomerular C1q-containing immune complexes. J Clin Invest 114:679–688

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

S.E-K. and H.J. supported by Helsinki University Hospital Research Foundation, A.M supported by Finska Läkäresällskapet and by EVO, Helsinki University Central Hospital.

Author information

Authors and Affiliations

  1. Department of Rheumatology, Peijas Hospital, Helsinki University Central Hospital, Vantaa, 01400, Finland

    Heikki Julkunen

  2. Department of Rheumatology, Helsinki University Central Hospital, Helsinki, Finland

    Susanne Ekblom-Kullberg

  3. Haartman Institute, University of Helsinki, Helsinki, Finland

    Aaro Miettinen

  4. Department of Immunology, HUSLAB, Helsinki University Central Hospital, Helsinki, Finland

    Aaro Miettinen

Authors
  1. Heikki Julkunen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susanne Ekblom-Kullberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aaro Miettinen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Heikki Julkunen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Julkunen, H., Ekblom-Kullberg, S. & Miettinen, A. Nonrenal and renal activity of systemic lupus erythematosus: a comparison of two anti-C1q and five anti-dsDNA assays and complement C3 and C4. Rheumatol Int 32, 2445–2451 (2012). https://doi.org/10.1007/s00296-011-1962-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-011-1962-3

Keywords

Search

Navigation