Antibodies directed against complement components and systemic lupus erythematosus
Authors:
P. Horák 1; H. Ciferská 1; J. Zadražil 1; Z. Heřmanová 2
Authors‘ workplace:
III. interní klinika, FN a LF UP Olomouc, 2 Oddělení klinické imunologie, FN Olomouc
1
Published in:
Čes. Revmatol., 16, 2008, No. 1, p. 16-22.
Category:
Overview Reports
Overview
SLE is a disease characterized by overproduction of various types of autoantibodies. Under certain circumstances, it is possible to detect the presence of autoantibodies directed against neoepitopes of complement system, as well. Neoepitopes are not present in native proteins, but develop with their structural alterations. The following antibodies come under known anticomplement auoantibodies: C3 nephritic factor, antibody directed against C1 inhibitor or antibodies directed against C1R (C1 receptor). Anti-C1q antibodies are concededly the most significant autoantibodies directed against complement system. They are present in about one third of patients with SLE and there is a correlation with clinical activity and the presence of lupus glomerulonephritis. High titers of anti-C1q antibodies are accompanied by decreased levels of C1, as well as C3 and especially C4 complement component. The presence of anti-C1q antibodies is not limited or specific for lupus only. They were described for the first time in case of HUVS (Hypocomplementemic Urticarial Vasculitis Sydrome), later in Felty’s syndrome, rheumatoid vasculitis, hepatitis C and in senescent population, as well. The association of anti-C1q antibodies, complement consumption and presence of renal affection in case of SLE calls into question, whether and how do these autoantibodies participate in organ affection pathogenesis. As shown in animal models of disease, the presence of both anti-dsDNA and anti-C1q antibodies is necessary for the genesis of lupus nephritis. Their mutual interaction triggers the mechanisms of development of renal affection mediated by immune complexes.
Key words:
systemic lupus erythematosus, complement system, anti-C1q antibodies
Sources
1. Sherer Y, Gorstein A, Fritzler M, Shoenfeld Y. Autoantibody explosion in systemic lupus erythematosus: More than 100 different antibodies found in SLE patients. Sem Arthritis Rheum 2004; 34: 501–537.
2. Walport MJ. Complement and systemic lupus erythematosus. Arthritis Res 2002; 4, Suppl.3: 279–293.
3. Pickering MC, Walport MJ. The complement system. In.: Hochberg MC, Silman AJ, Smolen JS, et al.: Rheumatology, Third Edition, Mosby, 2003, 1323–1336.
4. Cooper NR. The classical complement pathway: activation and regulation of first complement component. Adv Immunol 1985; 37: 151–216.
5. Fearon DT, Locksley RM. The instructive role of innate immunity in acquired immune response. Science 1996; 272: 50–53.
6. Carrol MC. The role of complement and complement receptors in induction and regulation of immunity. Annu Rev Immunol 1998; 6: 545–568.
7. Sim RB, Reid KB. C1: molecular interactions with activating systems. Immunol Today 1991; 12: 307–311.
8. Walport MJ, Ng YC, Lachmann PJ. Erythrocytes transfused into patients with SLE and haemolytic anaemia lose complement receptor type 1 from their cell surface. Clin Exp Immunol 1987; 69: 501–507.
9. Walport MJ, Davies KA, Botto M. C1q and systemic lupus erythematosus. Immunobiology 198;199: 265–285.
10. Herrmann M, Voll RE, Lolowos W, et al. Etiopathogenesis of systemic lupus erythematosus. Immunologist 2000; 8: 345–350.
11. Walport MJ. Advances in immunology: Complement (first of two parts). NEJM 2001; 344: 1058–1066.
12. Navratil JS, Korb LC, Ahearn JM. Systemic lupus erythematosus and complement deficiency: clues to a novel role for the classical complement pathway in the maintenance of immune tolerance. Immunopharmacol 1999; 42: 47–52.
13. Law SK, Lichtenberg NA, Holcombe FH, et al. Interaction between the labile binding sites of the fourth and fifth human complement proteins and erythrocyte cell membranes. J Immunol 1980; 125: 634–639.
14. Barilla-LaBarca ML, Atkinson JP. Rheumatic syndromes associated with complement deficiency. Curr Opin Rheumatol 2003; 15: 55–60.
15. Mitchell DA, Pickering MC, Warren J, et al. C1q deficiency and autoimmunity: the effects of genetic background on disease expression. J Immunol 2002; 168: 2538–2543.
16. Hauptmann G, Grosshans E, Heid E. Systemic lupus erythematosus and hereditary complement deficiency: A case with total C4 defect. Ann Dermatol Syphil Paris 1974; 101: 479–496.
17. Hannema AJ, Kluin-Nelemans JC, Hack CE, et al. SLE like syndrome and functional deficiency of C1q in members of a large family. Clin Exp Immunol 1984; 55:106–114.
18. Pickering MC, Botto M, Taylor PR, et al. (2000) Systemic lupus erythematosus, complement deficiency, and apoptosis. Adv Immunol 76: 227–324
19. Hauptmann G, Grosshans E, Heid E, et al. Lupus erythemateux aigu avec deficit complet de la fraction C4 du complement. Nouv Press Med 1974; 3: 881–882.
20. Schur PH. Inherited complement component abnormalities. Annu Rev Med 1986; 37: 333–346.
21. Ratnoff WD. Inherited deficiencies of complement in rheumatic diseases. Rheum Dis Clin N Am 1996; 22: 75–94.
22. Glass D, Raum D, Gibson D, et al. Inherited deficiency of the second component of complement. Rheumatic disease associations. J Clin Invest 1976; 58: 853–861.
23. Hauptmann G, Tappeiner G, Schifferli JA. Inherited deficiency of the fourth component of human complement. Immunodef Rev 1988; 1: 3–22.
24. Botto M, Walport MJ. C1q, autoimmunity and apoptosis. Immunobiol 2002; 205: 395–406.
25. Fielder AH, Walport MJ, Batchelor JR, et al. Family study of the major histocompatibility complex in patients with systemic lupus erythematosus: importance of null alleles of C4A and C4B in determining disease susceptibility. BMJ 1983;286: 425–428.
26. Christiansen FT, Dawkins RL, Uko G, et al. Complement allotyping in SLE: association with C4A null. Aust NZ J Med 1983; 13: 483–488.
27. Stone NM, Williams A, Wilkinson JD, et al. Systemic lupus erythematosus with C1q deficiency. Brit J Dermatol 2000; 142: 521–524.
28. Berkel AL, Petry F, Sanal O, et al. Development of systemic lupus erythematosus in a patient with selective complement C1q deficiency. Eur J Ped 1997;156: 113–115.
29. Botto M, Walport MJ. Hereditary deficiency of C3 in animals and humans. Int Rev Immunol 1993; 10: 37–50.
30. Pickering MC, Botto M, Taylor PR, et al. Systemic lupus erythematosus, complement deficiency, and apoptosis. Adv Immunol 2000; 76: 227–234.
31. Korb LC, Ahearn JM. C1q binds directly and specifically to surface blebs of apoptotic human keratinocytes: complement deficiency and systemic lupus erythematosus revisited. J Immunol 1997; 158: 4525–4528.
32. Prodeus AP, Gorg S, Shen LM, et al. A critical role of complement in maintenance of self tolerance. Immunity 1998; 9: 721–731.
33. Paul E, Carrol MC. SAP less chromatin triggers systemic lupus erythematosus. Nature Medicine 1999; 5: 607–608.
34. Gommerman JL, Carrol MC. Negative selection of B lymphocytes: a novel role for innate immunity. Immunol Rev 2000; 173: 120–130.
35. Trouw LA, Roos A, Daha MR. Autoantibodies to complement components. Mol Immunol 2001; 38: 199–206.
36. Seelen MA, Trouw LA, Daha MR. Diagnostic and prognostic significance of anti-C1q antibodies in systemic lupus erythematosus. Curr Opin Nephrol Hypertens 2003; 12: 619–624.
37. Agnello V, Koffler D, Eisenberg JW, et al. C1q 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 1971; 134: 228–241.
38. Trouw LA, Daha MR. Role of anti-C1q autoantibodies in the pathogenesis of lupus nephritis. Expert Opin Biol Ther 2005; 5: 243–251.
39. Trendelenburg M. Antibodies against C1q in patients with systemic lupus erythematosus. Springer Semin Immunopathol 2005; 27: 276–285.
40. Antes U, Heinz HP, Loos M. Evidence for the presence of autoantibodies to the collagen-like portion of C1q in systemic lupus erythematosus. Arthritis Rheum 1988; 31: 457–464.
41. Uwatoko S, Aotsuka S, Okawa, M, et al. C1q solid-phase radioimmunoassay: evidence for detection of antibody directed against the collagen-like region of C1q in sera from patients with systemic lupus erythematosus. Clin Exp Immunol 1987; 69: 98–106.
42. Uwatoko S, Mannik M. Low-molecular weight C1q-binding immunoglobulin G in patients with systemic lupus erythematosus consists of autoantibodies to the collagen-like region of C1q. J Clin Invest 1988; 82: 816–824.
43. Trouw LA, Groeneveld TW, Seelen MA, et al. Anti-C1q autoantibodies deposit in glomeruli but are only pathogenic in combination with glomerular C1q-containing immune complexes. J. Clin Invest 2004; 114: 679–688.
44. Holers VM. Anti-C1q autoantibodies amplify pathogenic complement activation in systemic lupus erythematosus. J Clin Invest 2004; 114: 616–619.
45. Flierman R, Daha R. Pathogenic role of anti C1q autoantibodies in the development of lupus nephritis – a hypotesis. Molecular Immunol 2007; 44: 133–138.
46. Horvath L, Czirjak L, Fekete B. High levels of antibodies against Clq are associated with disease activity and nephritis but not with other organ manifestations in SLE patients. Clin Exp Rheumatol 2001; 19: 667–672.
47. Siegert CE, Daha MR, Halma C, et al. IgG and IgA autoantibodies to C1q in systemic and renal diseases. Clin Exp Rheumatol 1992; 10: 19–23.
48. Siegert CE, Daha MR, Swaak AJ, et al. The relationship between serum titers of autoantibodies to C1q and age in the general population and in patients with systemic lupus erythematosus. Clin Immunol Immunopathol 1993; 67: 204–209.
49. Marto N, Bertolaccini ML, Calabuig E, et al. Anti-C1q antibodies in nephritis: correlation between titers and renal disease activity and positive predictive value in systemic lupus erythematosus. Ann Rheum Dis 2005; 64: 444–448.
50. Moroni G, Trendelenburg M , Del Papa N, et al. Anti-C1q antibodies may help in diagnosing a renal flare in lupus nephritis. Am J Kidney Dis 2001; 37: 490–498.
51. Coremans IE, Spronk PE, Bootsma H, et al. Changes in antibodies to C1q predict renal relapses in systemic lupus erythematosus. Am J Kidney Dis 1995; 26: 595–601.
52. Wisnieski JJ, Naff GB. Serum IgG antibodies to C1q in hypocomplementemic urticarial vasculitis syndrome. Arthritis Rheum 1989; 32: 1119–1127.
53. Trendelenburg M, Schifferli JA. Apoptosis and C1q: possible explanations for the pathogenesis of systemic lupus erythematosus. J Rheumatol 2000; 59: 172–175.
54. Lienesch DW, Sherman KE, Metzger A, et al. Anti-Clq antibodies in patients with chronic hepatitis C infection. Clin Exp Rheumatol 2006; 24: 183–185.
55. Saadoun D, Sadallah S, Trendelenburg M, et al. Anti-1q antibodies in hepatitis C virus infection. Clin Exp Immunol 2006; 145: 308–312.
56. Fremeaux-Bacchi V, Noel LH, Schifferli JA. No lupus nephritis in the absence of anti-C1q autoantibodies? Nephrol Dial Transplant 2002;17: 2041–2043.
57. Kumar A, Gupta R, Varghese T, et al. Anti-C1q antibody as a marker of disease activity in systemic lupus erythematosus. Indian J Med Res 1999; 10: 190–193.
58. Monova D, Monov S, Rosenova K, et al. Autoantibodies against C1q: view on association between systemic lupus erythematosus disease manifestation and C1q autoantibodies. Ann Rheum Dis 2002; 61: 563–564.
59. Trendelenburg M, Marfurt J, Gerber SA, et al. Lack of occurrence of severe lupus nephritis among anti-C1q autoantibody negative patients. Arthritis Rheum 1999; 42: 187–188.
60. Trendelenburg M, Lopez-Trascasa M, Potlukova E, et al. High prevalence of anti C1q antibodies in biopsy–proven active lupus nephritis, Nephrol Dial Transplant 2006; 21: 3115–3121.
61. Mosca M, Chimenti D, Pratesi F, et al. Prevalence and clinico-serological correlations of anti enolase, anti C1q, and dsDNA antibodies in patients with systemic lupus erythematosus J Rheumatol 2006; 33: 695–697.
62. Horák P, Heřmanová Z, Zadražil J, et al. C1q complement component and antibodies reflect SLE activity and kidney involvement. Clin Rheumatol 2006; 25: 532–536.
63. Kazatchkine MD, Fearon DT. Deficiencies of human complement receptors type 1 (CR1, CD35) and type 2 (CR2, CD21). Immunodef Rev 1990; 2: 17–41.
64. Iida K, Mornaghi R, Nussenzweig V. Complement receptor (CR) deficiency in erythrocytes from the patients with systemic lupus erythematosus. J Exp Med 1981; 155: 1427–38.
65. Tausk FA, McCutchan A, Spechko P, et al. Altered erythrocyte C3b receptor expression, immune complexes, and complement activation in homosexual men in varying risk groups for acquired immune deficiency syndrome. J Clin Invest 1986; 78: 977–82.
66. Kanto T, Hayashi N, Takehara T, et al. Low expression of erythrocyte complement receptor type 1 in chronic hepatitis C patients. J Med Virol 1996; 50: 126–34.
67. Sadallah S, Hess C, Trendelenburg M, et al. Autoantibodies against complement receptor 1 (CD35) in SLE, liver cirrhosis and HIV-infected patients Clin Exp Immunol 2003;131: 174–181.
68. Davies KA, Hird V, Stewart S, et al. A study of in vivo immune complex formation and clearance in man. J Immunol 1990; 144: 4613–4620.
69. Trouw LA, Roos A, Daha MR. Autoantibodies to complement components. Molecular Immunol 2001; 38: 199–206.
70. West CD, Witte DP, McAdams A. Composition of nephritic factor-generated glomerular deposits in membranoproliferative glomerulonephritis type 2. Am J Kidney Dis 2001; 37: 1120–1130.
71. D’Incan M, Tridon A, Ponard D, et al. Acquired angioedema with C1 inhibitor deficiency: Is the distinction between type I and type II still relevant? Dermatology 1999; 199: 227–230.
Labels
Dermatology & STDs Paediatric rheumatology RheumatologyArticle was published in
Czech Rheumatology
2008 Issue 1
Most read in this issue
- Antibodies directed against complement components and systemic lupus erythematosus
- Influence of supervised physical therapy on spinal mobility and pain in patients with ankylosing spondylitis
- Idiopathic retroperitoneal fibrosis: Less common cause of low back pain. Use of tamoxifen in the treatment of the diesease
- Cytokines BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand) and their role in autoimmune diseases