Role of nucleosomes for induction and glomerular binding of autoantibodies in lupus nephritis

Current Opinion in Nephrology and Hypertension

Volumn 8, Issue 3, 1999, Pages 299-306

  Berden, Jo H M ^a   Licht, Ruud ^a   Van Bruggen, Mieke C J ^a   Tax, Wil J M ^a  

^a RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINUCLEAR ANTIBODY; AUTOANTIBODY; AUTOANTIGEN; COLLAGEN TYPE 4; HEPARAN SULFATE; HISTONE;

ANTIGEN BINDING; APOPTOSIS; AUTOIMMUNITY; CROSS REACTION; GLOMERULUS BASEMENT MEMBRANE; HELPER CELL; HUMAN; IMMUNE RESPONSE; IMMUNOGENICITY; IMMUNOPATHOGENESIS; LUPUS ERYTHEMATOSUS NEPHRITIS; NUCLEOSOME; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; SYSTEMIC LUPUS ERYTHEMATOSUS; T LYMPHOCYTE ACTIVATION;

ANIMALS; ANTIBODIES, ANTINUCLEAR; APOPTOSIS; AUTOANTIBODIES; COLLAGEN; CROSS REACTIONS; HEPARITIN SULFATE; HUMANS; KIDNEY GLOMERULUS; LUPUS ERYTHEMATOSUS, SYSTEMIC; LUPUS NEPHRITIS; LYMPHOCYTE ACTIVATION; NUCLEOSOMES; T-LYMPHOCYTES, HELPER-INDUCER;

EID: 0032813046     PISSN: 10624821     EISSN: None     Source Type: Journal    
DOI: 10.1097/00041552-199905000-00005     Document Type: Review

References (57)

1. Berden JHM. Lupus nephritis. Nephrology Forum. Kidney Int 1997; 52:538-558. A recent review, which discusses new insights into the pathophysiology of lupus nephritis, together with treatment options and clinical aspects of end-stage renal disease in patients with lupus nephritis.
2. Tax WJM, Kramers C, van Bruggen MCJ, Berden JHM. Apoptosis, nucleosomes, and nephritis in systemic lupus erythematosus [Editorial review]. Kidney Int 1995; 48:666-673.
3. Amoura Z, Chabre H, Bach J, Koutouzov S. Antinucleosome antibodies and systemic lupus erythematosus. Adv Nephrol 1997; 26:303-316.
4. Casciola-Rosen LA, Rosen A. Ultraviolet light-induced keratinocyte apoptosis: a potential mechanism for the induction of skin lesions and autoantibody production in LE. Lupus 1997; 6:175-180. A description of the model whereby autoantigen fragments generated in apoptotic blebs initiate and drive the autoimmune response.
5. Mevorach D, Zhou JL, Song X, Elkon KB. Systemic exposure to irradiated apoptotic cells induces autoantibody production. J Exp Med 1998; 188:387-392. This study demonstrates that normal mice injected with syngeneic apoptotic cells develop antinuclear autoantibodies and glomerular deposition of IgG.
6. Cabrespines A, Laderach D, Lebosse C, Bach JF, Koutouzov S. Isolation and characterization of apoptotic nucleosomes, free and complexed with lupus autoantibody generated during hybridoma B-cell apoptosis. J Autoimmun 1998; 11:19-27.
7. Dianzani U, Bragardo M, DiFranco D, Alliaudi C, Scagni P, Buonfiglio D, et al. Deficiency of the Fas apoptosis pathway without Fas gene mutations in pediatric patients with autoimmunity/lymphoproliferation. Blood 1997; 89:2871-2879.
8. McNally J, Yoo DH, Drappa J, Chu JL, Yagita H, Friedman SM, Elkon KB. Fas ligand expression and function in systemic lupus erythematosus. J Immunol 1997; 159:4628-4636. The authors show that there are no specific defects in Fas ligand function in the majority of SLE patients.
9. Nakamura N, Ban T, Yamaji K, Yoneda Y, Wada Y. Localization of the apoptosis-inducing activity of lupus anticoagulant in an annexin V-binding antibody subset. J Clin invest 1998; 101:1951-1959.
10. Yang BC, Wang YS, Lin LC, Liu MF. Induction of apoptosis and cytokine gene expression in T-cell lines by sera of patients with systemic lupus erythematosus. Scand J Immunol 1997; 45:96-102.
11. Suzuki N, Ichino M, Mihara S, Kaneko S, Sakane T. Inhibition of Fas/Fas ligand-mediated apoptotic cell death of lymphocytes in vitro by circulating anti-Fas ligand autoantibodies in patients with systemic lupus erythematosus. Arthritis Rheum 1998; 41:344-353.
12. Emlen W, Niebur J, Kadera R. Accelerated in vitro apoptosis of lymphocytes from patients with systemic lupus erythematosus. J Immunol 1994; 152:3685-3692.
13. Lorenz HM, Grünke M, Hieronymus T, Herrmann M, Kühnel A, Manger B, Kalden JR. In vitro apoptosis and expression of apoptosis-related molecules in lymphocytes from patients with systemic lupus erythematosus and other autoimmune diseases. Arthritis Rheum 1997; 40:306-317.
14. Richardson BC, Yung RL, Johnson KJ, Rowse PE, Lalwani ND. Monocyte apoptosis in patients with active lupus. Arthritis Rheum 1996; 39:1432-1434.
15. Perniok A, Wedekind K, Herrmann M, Specker C, Schneider M. High levels of circulating early apoptic peripheral blood mononuclear cells in systemic lupus erythematosus. Lupus 1998; 7:113-118. Increased numbers of circulating apoptotic cells were observed in SLE patients irrespective of disease activity, suggesting that the increase (ascribed by the authors to impaired phagocytosis) may be a cause rather than a consequence of the disease.
16. Amoura Z, Piette JC, Chabre H, Cacoub P, Papo T, Wechsler B, et al. Circulating plasma levels of nucleosomes in patients with systemic lupus erythematosus: correlation with serum antinucleosome antibody titers and absence of clear association with disease activity. Arthritis Rheum 1997; 40:2217-2225. The identification of nucleosomes in the serum of lupus patients. Levels were not correlated with disease activity as assessed by SLEDAI but were inversely correlated with anti-nucleosome activity.
17. Budagyan VM, Bulanova EG, Sharova NI, Nikonova MF, Stanislav ML, Yarylin AA. The resistance of activated T-cells from SLE patients to apoptosis induced by human thymic stromal cells. Immunol Lett 1998; 60:1-5.
18. Mehrian R, Quismorio Jr FP, Strassmann G, Stimmler MM, Horwitz DA, Kitridou RC, et al. Synergistic effect between IL-10 and bcl-2 genotypes in determining susceptibility to systemic lupus erythematosus. Arthritis Rheum 1998; 41:596-602. In a large study in Mexican Americans, a strong association was found between SLE and specific genotypes of bcl-2 and IL-10.
19. Gregory CD. Phagocytic clearance of apoptotic cells: food for thought. Cell Death Diff 1998; 5:549-550.
20. Kalden JR. Defective phagocytosis of apoptotic cells: possible explanation for the induction of autoantibodies in SLE. Lupus 1997; 6:326-327.
21. Licht R, Jacobs CWM, Tax WJM, Berden JHM. An assay for the quantitative measurement of in vitro phagocytosis of early apoptotic thymocytes by resident peritoneal macrophages. J Immunol Methods 1999; 223:237-248.
22. Herrmann M, Voll RE, Zoller OM, Hagenhofer M, Ponner BB, Kalden JR. Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus. Arthritis Rheum 1998; 41:1241-1250. The first study reporting that macrophages from SLE patients have a decreased capacity to engulf apoptotic cells.
23. Walport MJ, Davies KA, Botto M. C1q deficiencies and C1q in autoimmunity. Immunobiology 1998; 199:265-285.
24. 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.
25. Botto M, Dell' Agnola C, Bygrave AE, Thompson ME, Cook HT, Petry F, et al. Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat Genet 1998; 19:56-59. In mice with a congenital C1q deficiency, anti-nuclear autoantibodies are formed, and 25% of these knock-out mice develop an immune complex glomerulonephritis with an increased number of apoptotic bodies in the glomerulus. These observations are explained by an impairment of apoptotic cell clearance caused by the C1q deficiency.
26. Manfredi AA, Rovere P, Heltai S, Galati G, Nebbia G, Tincani A, et al. Apoptotic cell clearance in systemic lupus erythematosus. II. Role of beta2-glycoprotein I. Arthritis Rheum 1998; 41:215-223.
27. Manfredi AA, Rovere P, Galati G, Heltai S, Bozzolo E, Soldini L, et al. Apoptotic cell clearance in systemic lupus erythematosus. I. Opsonization by antiphospholipid antibodies. Arthritis Rheum 1998; 41:205-214.
28. Laderach D, Bach J, Koutouzov S. Nucleosomes inhibit phagocytosis of apoptotic thymocytes by peritoneal macrophages from MRL +/+ lupus-prone mice. J Leukocyte Biol 1998; 64:774-780.
29. Voll RE, Herrmann M, Roth EA, Stach C, Kalden JR, Girkontaite I. Immunosuppressive effects of apoptotic cells. Nature 1997; 390:350-351. In the presence of apoptotic cells, lipopolysaccharide-activated monocytes produce substantially more of the anti-inflammatory cytokine IL-10, and less TNF-α, IL-1/β and IL-12.
30. Albert ML, Sauter B, Bhardwaj N. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 1998; 392:86-89. This study and [31] show that dendritic cells and macrophages, respectively, can generate T cell epitopes from engulfed apoptotic cells and present these in the content of MHC class I.
31. Bellone M, Iezzi G, Rovere P, Galati G, Ronchetti A, Protti MP, et al. Processing of engulfed apoptotic bodies yields T cell epitopes. J Immunol 1997; 159:5391-5399. See [30].
32. Kaliyaperumal A, Mohan C, Wu W, Datta SK. Nucleosomal peptide epitopes for nephritis-inducing T helper cells of murine lupus. J Exp Med 1996; 183:2459-2469.
33. Mohan C, Adams S, Stanik V, Datta SK. Nucleosome, a major immunogen for pathogenic autoantibody-inducing T cells of lupus. J Exp Med 1993; 177:1367-1381.
34. Datta SK, Kaliyaperumal A. Nucleosome-driven autoimmune response in lupus. Pathogenic T helper cell epitopes and costimulatory signals. Ann NY Acad Sci 1997; 815:155-170.
35. Shi Y, Kaliyaperumal A, Lu L, Southwood S, Sette A, Michaels MA, Datta SK. Promiscuous presentation and recognition of nucleosomal autoepitopes in lupus: role of autoimmune T cell receptor alpha chain. J Exp Med 1998; 187:367-378. Remarkable results were obtained when the recognition of nucleosomal epitopes by pathogenic T helper cells was analyzed. The T cell receptor recognized a core histone peptide in the context of MHC class II from all murine haplotypes tested, and even when bound to human DR molecules. Furthermore, only the alpha chain of the T cell receptor appeared to be relevant for binding.
36. Voll RE, Roth EA, Girkontaite I, Fehr H, Herrmann M, Lorenz HM, Kalden JR. Histone-specific Th0 and Th1 clones derived from systemic lupus erythematosus patients induce double-stranded DNA antibody production. Arthritis Rheum 1997; 40:2162-2171. After stimulation of mononuclear cells from SLE patients with autologous apoptotic cells, histone-specific T helper clones were obtained that could support the production of anti-dsDNA antibodies.
37. Rekvig OP, Moens U, Frederiksen K, Traavik T. Human polyoma virus BK and immunogenicity of mammalian DNA: a conceptual framework. Methods 1997;11:44-54. A model is described in which the in-vivo expression of a DNA-binding protein derived from polyomavirus induces the production of antibodies directed against mammalian dsDNA and nucleosomes in non-autoimmune mice. Polyomavirus reactivations often occur in SLE patients.
38. Rosen A, Casciola-Rosen L, Ahearn J. Novel packages of viral and self-antigens are generated during apoptosis. J Exp Med 1995; 181:1557-1561.
39. Utz PJ, Anderson P. Posttranslational protein modifications, apoptosis, and the bypass of tolerance to autoantigens. Arthritis Rheum 1998; 41:1152-1160. An excellent review of the different mechanisms that can induce autoantigen modification during apoptosis. The possible consequences of these modifications for the loss of tolerance for these autoantigens are discussed. On the basis of these observations a hypothesis for autoantibody formation is proposed.
40. Utz PJ, Hottelet M, Schur PH, Anderson P. Proteins phosphorylated during stress-induced apoptosis are common targets for autoantibody production in patients with systemic lupus erythematosus. J Exp Med 1997; 185:843-854.
41. L gene usage, and pathogenicity.
42. Brard F, Petit S, Coquerel G, Gilbert D, Koutouzov S, Perez G, Tron F. Modeling of anti-nucleosorne immunoglobulin Fv domains: analysis of electrostatic interactions. Mol Immunol 1997; 34:793-807.
43. Berden JHM, Smeenk RJT. Nucleosome-specific auto-antibodies. In: Autoantibodies. Peter JB, Shoenfeld Y (editors). Amsterdam: Elsevier; 1996. pp. 574-581.
44. Stemmer C, Briand JP, Muller S. Mapping of linear histone regions exposed at the surface of the nucleosome in solution. J Mol Biol 1997; 273:52-60. A large scale analysis of histone epitopes accessible at the surface of nucleosomes by using monoclonal and polyclonal antibodies to 40 overlapping synthetic peptides covering the whole sequence of the four core histones. This revealed that the N terminal regions of H2A, H2B and H3 are exposed, together with the C terminal portions of H2A and H4. In addition six domains were located in the internal segments of the core histones.
45. Kramers C, Hylkoma MN, van Bruggen MCJ, van de Lagemaat R, Dijkman HBPM, Assmann KJM, et al. Anti-nucleosome antibodies complexed to nucleosomal antigens show anti-DNA reactivity and bind to rat glomerular basement membrane in vivo. J Clin Invest 1994; 94:568-577.
46. Lefkowith JB, Gilkeson GS. Nephritogenic auto-antibodies in lupus. Arthritis Rheum 1996; 39:894-903.
47. Foster MH, Cizman B, Madaio MP. Biology of disease. Nephritogenic autoantibodies in systemic lupus erythematosus: immunochemical properties, mechanisms of immune deposition, and genetic origin. Lab Invest 1993; 69:494-507.
48. D'Andrea DM, Coupaye-Gerard B, Kleyman TR, Foster MH, Madaio MP. Lupus autoantibodies interact directly with distinct glomerular and vascular cell surface antigens. Kidney Int 1996; 49:1214-1221.
49. Ravirajan CT, Pahman MA, Papadaki L, Griffiths MH, Kalsi JK, Martin AC, et al. Genetic, structural and functional properties of an IgG DNA-binding monoclonal antibody from a lupus patient with nephritis. Eur J Immunol 1998; 281:339-350. Analysis of the nephritogenic properties of two human anti-DNA mAbas by intraperitoneal inoculation of hybridomas. Only the clone (RH-14) that reacted with DNA and nucleosomes was pathogenic in contrast to the mAb that exclusively bound to dsDNA.
50. Budhai L, Oh K, Davidson A. An in vitro assay for detection of glomerular binding IgG autoantibodies in patients with systemic lupus erythematosus. J Clin Invest 1996; 98:1585-1593.
51. Raz E, Brezis M, Rosenmann E, Eilat D. Anti-DNA antibodies bind directly to renal antigens and induce kidney dysfunction in the isolated perfused rat kidney. J Immunol 1989; 142:3076-3082.
52. Gaynor B, Putterman C, Valadon P, Spatz L, Scharff MD, Diamond B. Peptide inhibition of glomerular deposition of an anti-DNA antibody. Proc Natl Acad Sci USA 1997; 94:1955-1960. Using a peptide display phage library, peptides were identified that were able to inhibit the binding of a pathogenic mAb (R4A) to dsDNA, whereas dsDNA inhibited the binding to this peptide. Co-injection of the peptide and the mAbs inhibited the glomerular binding of the mAb in vivo.
53. van Bruggen MCJ, Walgreen B, Rijke GPM, Kramers C, Smeenk RJT, Monestier M, et al. Antigen specificity of antinuclear antibodies complexed to nucleosomes determines glomerular basement membrane binding in vivo. Eur J Imrnunol 1997; 27:1564-1569. Analysis of the influence of the specificity of the anti-nuclear antibody bound to nucleosomes for the nephritogenic potential of the nucleosome/anti-nuclear antibody complex. Hybridomas secreting either anti-histone, anti-dsDNA or nucleosome-specific mAbs were inoculated in nude mice. Despite similar levels of nucleosome-IgG complexes, glomerular binding was less (15% of animals) in mice carrying anti-histone hybridomas than mice inoculated with nucleosome-specific or anti-dsDNA hybridomas (60% of animals positive).
54. van Bruggen MCJ, Walgreen B, Rijke GPM, Corsius MJAMM, Assmann KJM, et al. Heparin and heparinoids prevent the binding of immune complexes containing nucleosomal antigens to the GBM and delay nephritis in MRL/I mice. Kidney Int 1996; 50:1555-1564.
55. van Bruggen MCJ, Kramers C, Walgreen B, Elema JD, Kallenberg CGM, van den Born J, et al. Nucleosomes and histones are present in glomerular deposits in human lupus nephritis. Nephrol Dial Transplant 1997; 12:57-66. The first demonstration of nucleosomes in glomerular deposits in human lupus nephritis.
56. Termaat RM, Assmann KJM, Dijkman HBPM, Smeenk RJT, Berden JHM. Anti-DNA antibodies can bind to the glomerulus via two distinct mechanisms. Kidney Int 1992; 42:1363-1371.
57. Lefkowith JB, Kiehl M, Rubenstein J, DiValerio R, Bernstein K, Kahl L, Rubin RL, Gourley MF. Heterogeneity and clinical significance of glomerular binding antibodies in systemic lupus erythematosus. J Clin Invest 1996; 98:1373-1380.