Skip to main content
SpringerLink
Log in

C1q-bearing immune complexes detected by a monoclonal antibody to human C1q in rheumatoid arthritis sera and synovial fluids

  • Published:
Rheumatology International Aims and scope Submit manuscript

Summary

Using a monoclonal antibody directed against the C-chain of human C1q, we detected C1q-bearing immune complexes (IC) in sera and synovial fluids of rheumatoid arthritis (RA) patients. In a sandwich-ELISA, C1q-bearing IC were captured by the solid-phase monoclonal antibody and then detected with peroxidase-labeled F(ab′)2-antibodies to either human IgG or IgM. The results of this assay were compared to an ELISA-modification of the C1q-solid-phase binding assay (C1q-SPBA). C1q-bearing IC were detected in 81.1% of RA-sera and the 65.2% of RA-synovial fluids. IgG as well as IgM was present in 72.6% of the sera and 70% of the synovial fluids which were positive in both assays. Most RA sera that were only positive for C1q-bearing IC, contained IgG alone (81.5%). The corresponding synovial fluids showed IgG alone (53%) or both IgG and IgM (41.1%). IgM alone (25%) could be detected in sera, e.g. in juvenile forms of RA. The levels of IC were higher in synovial fluid than in paired serum. In comparison to normal human serum (NHS) and patients with osteoarthritis, complement activity (CH50 titers) and C1q-values in patients with RA were frequently elevated. Since the formation of C1q-bearing IC is an indicator for the classical complement pathway activation, an assay with monoclonal anti-C1q antibody may be a useful tool in the diagnosis of rheumatoid diseases.

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. Zubler RH, Lambert PH (1978) Detection of immune complexes in human diseases. Prog Allergy 24: 1–48

    Google Scholar 

  2. Theofilopoulos AN, Dixon FJ (1979) The biology and detection of immune complexes. Adv Immunol 28: 89–221

    Google Scholar 

  3. Lambert PH, Dixon FJ, Zubler RH, Agnello V et al. (1978) A WHO collaborative study for the evaluation of eighteen methods for detecting immune complexes in Serum. J Clin Lab Immunol 1: 1–15

    Google Scholar 

  4. Loos M, Borsos T, Rapp HJ (1972) Activation of the first component of complement. Evidence for an internal activation step. J Immunol 108: 683–688

    Google Scholar 

  5. Lin TS, Fletcher DS (1978) Interaction of human C1q with insoluble immunoglobulin aggregates. Immunochemsitry 15: 107–117

    Google Scholar 

  6. Loos M (1982) The classical complement pathway: mechanism of activation of the first component by antigen-antibody complexes. Prog Allergy 30: 135–192

    Google Scholar 

  7. Cooper NR (1985) The classical complement pathway: activation and regulation of the first complement component. Adv Immunol 37: 151

    Google Scholar 

  8. Ziccardi RJ (1983) The first component of human complement (C1): activation and control. Springer Semin Immunopathol 6: 213–230

    Google Scholar 

  9. 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 

  10. Heinz H-P, Burger R, Golan MD, Loos M (1984) Activation of the first component of complement, C1, by a monoclonal antibody recognizing the C chain of C1q. J Immunol 132: 804

    Google Scholar 

  11. 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 

  12. Arnett CF, Edworthy SM, Block DA et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31: 315

    Google Scholar 

  13. Golan MD, Burger R, Loos M (1982) Conformational changes in C1q after binding to immune complexes: detection of neoantigens with monoclonal antibodies. J Immunol 129: 445–447

    Google Scholar 

  14. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 139: 265

    Google Scholar 

  15. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680

    Google Scholar 

  16. 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 

  17. Heinz H-P, Hitschold T, Latsch M, Loos M (1985) Vereinfachter Mikroassay zur Bestimmung der gesamthämolytischen Komplementaktivität, CH50. Lab Med 9: 320–323

    Google Scholar 

  18. Golan MD, Hitschold T, Loos M (1981) The reconstitution of human C1, the first complement component. FEBS Lett 128: 281–285

    Google Scholar 

  19. Antes U, Heinz H-P, Loos M (1984) Enzyme linked immunosorbent assay for C1q in human serum by use of monoclonal antibodies. J Immunol Methods 74: 299–306

    Google Scholar 

  20. Nydegger UE, Svehag SE (1984) Improved standardization in the quantitative estimation of soluble immune complexes making use of an international reference preparation. Results of a collaborative multicentre study. Clin Exp Immunol 58: 502–509

    Google Scholar 

  21. Hay FC, Nineham LJ, Roiatt IM (1976) Routine assay for the detection of immune complexes of known immunoglobulin class using solid phase C1q. Clin Exp Immunol 24: 396–400

    Google Scholar 

  22. Halla JT, Volanakis JE, Schrohenloher RE (1979) Immune complexes in rheumatoid arthritis sera and synovial fluids. Arthritis Rheum 22: 440–448

    Google Scholar 

  23. Vanham G, Bloemmen FJ, Ceuppens JL, Stevens EAM (1984) Influence of serum complement and rheumatoid factor on detection of IC by the C1q and monoclonal rheumatoid factor solid-phase assay. J Immunol Methods 73: 301–311

    Google Scholar 

  24. Wener MH, Mannik M (1983) Influence of immune complex lattice on the C1q solid phase assay as determined with covalently cross-linked immune complexes. Clin Exp Immunol 52: 543–550

    Google Scholar 

  25. Hack CE, Belmer AJM (1986) The IgG detected in the C1q solid-phase immune complex assay is not always of immune-complex nature. Clin Immunol Immunopathol 38: 120–128

    Google Scholar 

  26. Luthra HS, McDuffie FC, Hunder GG, Samayoa EA (1975) Immune complexes in sera and synovial fluids of patients with rheumatoid arthritis. Radioimmunoassay with monoclonal rheumatoid factor. J Clin Invest 56: 458–466

    Google Scholar 

  27. Reckel RP, Harris J, Botsko R, Wellerson R, Varga S (1984) The detection of circulating immune complexes containing C1q and IgG using a new rapid serum ELISA test system. Diagn Immunol 2: 228–237

    Google Scholar 

  28. Williams RC (1983) Rheumatoid factor. Hum Pathol 15: 386–391

    Google Scholar 

  29. Whaley K (1987) Complement and immune complex diseases. In: Whaley K (ed) Complement in health and disease. MTP, Lancaster, pp 163–183

    Google Scholar 

  30. Ruddy S, Colten HR (1974) Rheumatoid arthritis biosynthesis of complement proteins by synovial tissues. N Engl J Med 290: 1284–1288

    Google Scholar 

  31. Katz Y, Strunk RC (1988) Synovial fibroblast-like cells synthesize seven proteins of the complement system. Arthritis Rheum 31: 1365–1370

    Google Scholar 

  32. Ghebrehiwet B (1989) Functions associated with the C1q receptor. Behring Inst Mitt 84: 204–215

    Google Scholar 

  33. Walport MJ, Lachmann PJ (1988) Erythrocyte complement receptor type 1, immune complexes, and the rheumatic diseases. Arthritis Rheum 31: 153–158

    Google Scholar 

  34. Male D, Roitt IM, Hay FC (1980) Analysis of immune complexes in synovial effusions of patients with rheumatoid arthritis. Clin Exp Immunol 39: 297–306

    Google Scholar 

  35. Inman RD, Hamilton NC, Redecha PB, Hochhauser DM (1986) Electrophoretic transfer blotting analysis of immune complexes in rheumatoid arthritis. Clin Exp Immunol 63: 32–40

    Google Scholar 

  36. Kilgallon W, Amlot PL, Williams BD (1982) Anti-C1q column: ligand specific purification of immune complexes from human serum or plasma. Analysis of the interaction between C1q and immune complexes. Clin Exp Immunol 48: 705–714

    Google Scholar 

  37. Hauptmann SP, Sobczak G (1976) Origin of immunoglobulin albumin complex. Nature 263: 64

    Google Scholar 

  38. Inman RD, Harpel PC (1983) C1 inactivator — C1s complexes in inflammatory joint disease. Clin Exp Immunol 53: 521

    Google Scholar 

  39. Sjöholm AG, Berglund K, Johnson U, Laurell A-B, Sturfelt G (1986) C1 activation with C1q in excess of functional C1 in synovial fluid from patients with rheumatoid arthritis. Int Arch Allergy Appl Immunol 79: 113–119

    Google Scholar 

  40. Jones VE, Jacoby RK, Wallington T, Holt P (1981) Immune complexes in early arthritis. I. Detection of immune complexes before rheumatoid arthritis is definite. Clin Exp Immunol 44: 512–521

    Google Scholar 

  41. Jones V, Jacoby RK, Cowley PJ, Warren C (1982) Immune complexes in early arthritis. II. Immune complex constituents are synthesized in the synovium before rheumatoid factors. Clin Exp Immunol 49: 31

    Google Scholar 

  42. Hay FC, Young A, Jones MG, Nineham J, Male DK, Roitt IM (1983) Anti-globulins and circulating complexes in early rheumatoid arthritis. Clin Exp Immunol 54: 723–730

    Google Scholar 

  43. Loos M (1982) The classical complement pathway: mechanism of activation of the first component by antigen-antibody complexes. Prog Allergy 30: 135–192

    Google Scholar 

  44. Barnett EV (1986) Circulating immune complexes: their biological and clinical significance. J Allergy Clin Immunol 78: 1089–1096

    Google Scholar 

  45. Schultz DR, Loos M, Arnold PT (1980) Differentiation of hemolytically active fluid-phase and cellbound C1q by an ant venom-derived polysaccharide. J Immunol 124: 1251–1257

    Google Scholar 

  46. Heinz H-P (1989) Biological functions of C1q expressed by conformational changes. Behring Inst Mitt 84: 20–31

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Medical Microbiology, Johannes Gutenberg-University, W-6500, Mainz, Germany

    U. Antes, H. -P. Heinz & M. Loos

  2. Department of Medicine, University of Miami, Miami, Florida, USA

    D. Schultz

  3. St. Vincent and Elisabeth Hospital, Mainz, Germany

    D. Brackertz

Authors
  1. U. Antes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. -P. Heinz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Schultz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Brackertz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Loos
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Antes, U., Heinz, H.P., Schultz, D. et al. C1q-bearing immune complexes detected by a monoclonal antibody to human C1q in rheumatoid arthritis sera and synovial fluids. Rheumatol Int 10, 245–250 (1991). https://doi.org/10.1007/BF02274887

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02274887

Key words

Search

Navigation