Home LiteratureArticle Details
PMID: 9486404 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Anti-C1q receptor/calreticulin autoantibodies in patients with systemic lupus erythematosus (SLE).

Clinical and experimental immunology ·Vol. 111 ·No. 2 ·1998-02-00 ·Pages 359-64

van den Berg RH, Siegert CE, Faber-Krol MC, Huizinga TW, van Es LA, Daha MR

Abstract

SLE is a disease characterized by the presence of multiple autoantibodies and high levels of circulating immune complexes. We studied the presence and functional relevance of autoantibodies directed against a receptor for the collagen-like stalks of the first subcomponent of complement, also known as calreticulin (cC1qR/CaR), in patients with SLE. In a cross-sectional study it was found that higher titres of antibodies against cC1qR/CaR are present in sera of SLE patients compared with normal donors. No association between anti-cC1qR/CaR titres and SLE disease activity was found. Following gel filtration of SLE serum it was found that anti-cC1qR/CaR reactivity is associated with the peak of monomeric IgG. Purified IgG from patients was able to specifically immunoprecipitate cC1qR/CaR. Since we have shown previously that cC1qR/CaR is able to inhibit the haemolytic activity of Clq, we determined a possible pathogenic role for anti-cC1qR/CaR on complement regulation. IgG derived from SLE serum reversed the inhibitory capacity of cC1qR/CaR in a dose-dependent fashion up to 63%, whereas IgG from normal donors had no significant effect. With respect to the capacity of anti-cC1qR/CaR antibodies to activate neutrophils, it was found that incubation of normal neutrophils with F(ab')2 anti-cC1qR/CaR resulted in a very limited oxidative burst. However, cross-linking of F(ab')2 anti-cC1qR/CaR on the neutrophils clearly induced neutrophil activation. Pre-incubation of the SLE-derived F(ab')2 with cC1qR/CaR prevented activation of neutrophils up to 81+/-5%. These results suggest that the presence of anti-cC1qR/CaR antibodies in patients with SLE may modulate complement and neutrophil activation.

MeSH Terms
Antibody Specificity Autoantibodies/blood,immunology Calcium-Binding Proteins/immunology Calreticulin Carrier Proteins Complement Activation/immunology Complement C1q/immunology Enzyme-Linked Immunosorbent Assay Hemolysis Humans Hyaluronan Receptors Immunoglobulin Fragments/pharmacology Lupus Erythematosus, Systemic/blood,immunology Membrane Glycoproteins Mitochondrial Proteins Neutrophil Activation/immunology Neutrophils/immunology Receptors, Complement/immunology Ribonucleoproteins/immunology Sensitivity and Specificity
Chemicals
Autoantibodies C1QBP protein, human Calcium-Binding Proteins Calreticulin Carrier Proteins Hyaluronan Receptors Immunoglobulin Fragments Membrane Glycoproteins Mitochondrial Proteins Receptors, Complement Ribonucleoproteins complement 1q receptor Complement C1q
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
van den Berg R H
Department of Nephrology, Leiden University Hospital, The Netherlands.
Siegert C E
Faber-Krol M C
Huizinga T W
van Es L A
Daha M R
References (43)
43 references, click to expand
  1. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  2. The systemic lupus erythematosus (SLE) disease autoantigen-calreticulin can inhibit C1q association with immune complexes.
    Clin Exp Immunol. 1997 May;108(2):181-90 PMID: 9158084
  3. Autoantibodies and the spectrum of Sjögren's syndrome.
    Ann Intern Med. 1979 Aug;91(2):185-90 PMID: 157095
  4. Correlation and predictive accuracy of circulating immune complexes with disease activity in patients with systemic lupus erythematosus.
    Arthritis Rheum. 1980 Mar;23(3):273-82 PMID: 6987992
  5. Analysis of receptor-mediated C1q binding to human peripheral blood mononuclear cells.
    J Immunol. 1980 Oct;125(4):1658-64 PMID: 7410850
  6. Immune complexes, complement, and anti-DNA in exacerbations of systemic lupus erythematosus (SLE).
    Medicine (Baltimore). 1981 May;60(3):208-17 PMID: 7231154
  7. The classical complement pathway: mechanism of activation of the first component by antigen-antibody complexes.
    Prog Allergy. 1982;30:135-92 PMID: 7041131
  8. Pathophysiology of circulating immune complexes.
    Arthritis Rheum. 1982 Jul;25(7):783-7 PMID: 6213236
  9. Complement and lupus erythematosus.
    Arthritis Rheum. 1982 Jul;25(7):793-8 PMID: 7049183
  10. Serologic and HLA associations in subacute cutaneous lupus erythematosus, a clinical subset of lupus erythematosus.
    Ann Intern Med. 1982 Nov;97(5):664-71 PMID: 6982644
  11. The 1982 revised criteria for the classification of systemic lupus erythematosus.
    Arthritis Rheum. 1982 Nov;25(11):1271-7 PMID: 7138600
  12. C1Q receptors on cultured human gingival fibroblasts: analysis of binding properties.
    J Immunol. 1983 Apr;130(4):1871-5 PMID: 6339617
  13. Binding of cytoskeletal proteins by monoclonal anti-DNA lupus autoantibodies.
    Clin Immunol Immunopathol. 1984 May;31(2):261-71 PMID: 6370522
  14. The classical complement pathway: activation and regulation of the first complement component.
    Adv Immunol. 1985;37:151-216 PMID: 3890478
  15. Autoantibody to the C3b/C4b receptor and absence of this receptor from erythrocytes of a patient with systemic lupus erythematosus.
    J Clin Invest. 1985 Jul;76(1):182-90 PMID: 4019777
  16. The role of complement and its receptor in the elimination of immune complexes.
    N Engl J Med. 1986 Aug 21;315(8):488-95 PMID: 2942776
  17. Complement activation during systemic lupus erythematosus. C3a and C5a anaphylatoxins circulate during exacerbations of disease.
    Arthritis Rheum. 1986 Sep;29(9):1085-9 PMID: 3489467
  18. Human blood platelets possess specific binding sites for C1q.
    J Immunol. 1987 Mar 1;138(5):1537-41 PMID: 3492557
  19. C1q inhibits the expression of B lymphoblastoid cell line interleukin 1 (IL 1).
    J Immunol. 1987 Apr 15;138(8):2593-7 PMID: 3494080
  20. C1q enhancement of antibody-dependent granulocyte-mediated killing of nonphagocytosable targets in vitro.
    J Clin Invest. 1988 Sep;82(3):945-9 PMID: 2843577
  21. Physiological and pathological aspects of circulating immune complexes.
    Kidney Int. 1989 Apr;35(4):993-1003 PMID: 2651776
  22. A novel assay for neutrophil clustering activity of human sera: relation to disease activity and neutropenia in systemic lupus erythematosus.
    Ann Rheum Dis. 1990 Jan;49(1):46-50 PMID: 2310227
  23. IgG autoantibodies against C1q are correlated with nephritis, hypocomplementemia, and dsDNA antibodies in systemic lupus erythematosus.
    J Rheumatol. 1991 Feb;18(2):230-4 PMID: 2023216
  24. Characterization of the autoantigen calreticulin.
    J Immunol. 1991 Nov 1;147(9):3031-9 PMID: 1919005
  25. The role of C3 in the immune response.
    Immunol Today. 1991 Sep;12(9):332-7 PMID: 1755944
  26. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE.
    Arthritis Rheum. 1992 Jun;35(6):630-40 PMID: 1599520
  27. The calcium-binding protein calreticulin is a major constituent of lytic granules in cytolytic T lymphocytes.
    J Exp Med. 1993 Jan 1;177(1):1-7 PMID: 8418194
  28. Structure and homology of human C1q receptor (collectin receptor).
    Immunology. 1993 Mar;78(3):341-8 PMID: 8478019
  29. An acute model for IgA-mediated glomerular inflammation in rats induced by monoclonal polymeric rat IgA antibodies.
    Clin Exp Immunol. 1993 Jun;92(3):514-21 PMID: 8099859
  30. C1Q, a subunit of the first component of complement, enhances the binding of aggregated IgG to rat renal mesangial cells.
    J Immunol. 1993 Oct 15;151(8):4315-24 PMID: 8409404
  31. Cleavage and inactivation of human C1 inhibitor by the human leukocyte proteinase, proteinase 3.
    Eur J Immunol. 1993 Nov;23(11):2939-44 PMID: 8223871
  32. Cell-surface protein identified on phagocytic cells modulates the C1q-mediated enhancement of phagocytosis.
    J Immunol. 1994 Apr 15;152(8):4005-16 PMID: 8144968
  33. Isolation, cDNA cloning, and overexpression of a 33-kD cell surface glycoprotein that binds to the globular "heads" of C1q.
    J Exp Med. 1994 Jun 1;179(6):1809-21 PMID: 8195709
  34. Novel functions for calreticulin: interaction with integrins and modulation of gene expression?
    Trends Biochem Sci. 1994 Jul;19(7):269-71 PMID: 8048166
  35. Calreticulin is released from activated neutrophils and binds to C1q and mannan-binding protein.
    Clin Immunol Immunopathol. 1994 Sep;72(3):405-9 PMID: 8062452
  36. Viral induction of the human autoantigen calreticulin.
    Clin Invest Med. 1994 Jun;17(3):196-205 PMID: 7923996
  37. Identification of a gC1q-binding protein (gC1q-R) on the surface of human neutrophils. Subcellular localization and binding properties in comparison with the cC1q-R.
    J Clin Invest. 1995 Apr;95(4):1569-78 PMID: 7706463
  38. Cell surface calreticulin is a putative mannoside lectin which triggers mouse melanoma cell spreading.
    J Biol Chem. 1995 Jul 7;270(27):15926-9 PMID: 7608143
  39. Chaperone function of calreticulin when expressed in the endoplasmic reticulum as the membrane-anchored and soluble forms.
    J Biol Chem. 1995 Sep 1;270(35):20298-304 PMID: 7657600
  40. Regulation of the function of the first component of complement by human C1q receptor.
    Eur J Immunol. 1995 Aug;25(8):2206-10 PMID: 7664783
  41. Localisation of the C1q binding site within C1q receptor/calreticulin.
    FEBS Lett. 1996 Nov 18;397(2-3):245-9 PMID: 8955356
  42. Release of calreticulin from neutrophils may alter C1q-mediated immune functions.
    Biochem J. 1997 Mar 1;322 ( Pt 2):543-50 PMID: 9065775
  43. Serum immune complexes and disease activity in lupus nephritis.
    Lancet. 1977 Mar 12;1(8011):564-7 PMID: 65659
Article Info
Journal
Clinical and experimental immunology
Abbr.
Clin Exp Immunol
ISSN
0009-9104
DOI
10.1046/j.1365-2249.1998.00473.x
Published
1998-02-00
Pages
359-64
Language
English
Region
England
NLM ID
0057202
PMCID
PMC1904908
Subset
IM
External Links
PubMed source DOI: 10.1046/j.1365-2249.1998.00473.x PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2