The Tolerogenic Peptide, hCDR1, Down-Regulates the Expression of Interferon-α in Murine and Human Systemic Lupus Erythematosus

PLoS ONE

Volumn 8, Issue 3, 2013, Pages

  Sthoeger, Zev ^a,b   Zinger, Heidy ^a   Sharabi, Amir ^a   Asher, Ilan ^b   Mozes, Edna ^a  

^a WEIZMANN INSTITUTE OF SCIENCE   (Israel)

^b KAPLAN MEDICAL CENTER   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERFERON; DOUBLE STRANDED DNA ANTIBODY; EDRATIDE; INTERLEUKIN 1BETA; MESSENGER RNA; PLACEBO; RECOMBINANT ALPHA INTERFERON; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA;

ADULT; AGED; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIPHOSPHOLIPID SYNDROME; ARTICLE; BRITISH ISLETS LUPUS ASSESSMENT GROUP SCORE; CLINICAL ARTICLE; CONTROLLED STUDY; DISEASE ACTIVITY; DOWN REGULATION; FEMALE; GENE EXPRESSION; HUMAN; HUMAN CELL; IMMUNOMODULATION; MALE; MOUSE; NONHUMAN; PERIPHERAL BLOOD MONONUCLEAR CELL; PROTEINURIA; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SCORING SYSTEM; SLEDAI; SPLEEN CELL; SYSTEMIC LUPUS ERYTHEMATOSUS;

AMINO ACID SEQUENCE; ANIMALS; AUTOANTIGENS; CELLS, CULTURED; DOWN-REGULATION; FEMALE; HUMANS; IMMUNOLOGIC FACTORS; INTERFERON-ALPHA; LEUKOCYTES, MONONUCLEAR; LUPUS ERYTHEMATOSUS, SYSTEMIC; MALE; MICE; MOLECULAR SEQUENCE DATA; NERVE TISSUE PROTEINS; PEPTIDES;

MURINAE; MUS;

EID: 84875549170     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0060394     Document Type: Article

References (49)

1. Tsokos GC, (2011) Systemic lupus erythematosus. N Engl J Med 365: 2110-2121.
2. Horwitz DA, Jacob CO, (1994) The cytokine network in the pathogenesis of systemic lupus erythematosus and possible therapeutic implications. Springer Semin Immunopathol 16: 181-200.
3. Segal R, Bermas BL, Dayan M, Kalush F, Shearer GM, et al. (1997) Kinetics of cytokine production in experimental systemic lupus erythematosus: involvement of T helper cell 1/T helper cell 2-type cytokines in disease. J Immunol 158: 3009-3016.
4. Cheema GS, Roschke V, Hilbert DM, Stohl W, (2011) Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases. Arthritis Rheum 44: 1313-1319.
5. Trébéden-Nègre H, Weill B, Fournier C, Batteux F, (2003) B cell apoptosis accelerates the onset of murine lupus. Eur J Immunol 33: 1603-1612.
6. Emlen W, Niebur J, Kadera R, (1994) Accelerated in vitro apoptosis of lymphocytes from patients with systemic lupus erythematosus. J Immunol 152: 3685-3692.
7. Valencia X, Yarboro C, Illei G, Lipsky PE, (2007) Deficient CD4+CD25high T regulatory cell function in patients with active systemic lupus erythematosus. J Immunol 178: 2579-2588.
8. Paust S, Cantor H, (2005) Regulatory T cells and autoimmune disease. Immunol Rev 204: 195-207.
9. Mozes E, Sharabi A, (2010) A novel tolerogenic peptide, hCDR1, for the specific treatment of systemic lupus erythematosus. Autoimmun Rev 10: 22-26.
10. Waisman A, Shoenfeld Y, Blank M, Ruiz PJ, Mozes E, (1995) The pathogenic human monoclonal anti-DNA that induces experimental systemic lupus erythematosus in mice is encoded by a VH4 gene segment. Int Immunol 7: 689-696.
11. Luger D, Dayan M, Zinger H, Liu JP, Mozes E, (2004) A peptide based on the complementarity determining region 1 of a human monoclonal autoantibody ameliorates spontaneous and induced lupus manifestations in correlation with cytokine immunomodulation. J Clin Immunol 24: 579-590.
12. Sharabi A, Haviv A, Zinger H, Dayan M, Mozes E, (2006) Amelioration of murine lupus by a peptide, based on the complementarity determining region-1 of an autoantibody as compared to dexamethasone: different effects on cytokines and apoptosis. Clin Immunol 119: 146-155.
13. Sela U, Hershkoviz R, Cahalon L, Lider O, Mozes E, (2005) Down-regulation of stromal cell-derived factor-1alpha-induced T cell chemotaxis by a peptide based on the complementarity-determining region 1 of an anti-DNA autoantibody via up-regulation of TGF-beta secretion. J Immunol 174: 302-309.
14. Sela U, Dayan M, Hershkoviz R, Cahalon L, Lider O, et al. (2006) The negative regulators Foxj1 and Foxo3a are up-regulated by a peptide that inhibits systemic lupus erythematosus-associated T cell responses. Eur J Immunol 36: 2971-2980.
15. Sharabi A, Zinger H, Zborowsky M, Sthoeger ZM, Mozes E, (2006) A peptide based on the complementarity-determining region 1 of an autoantibody ameliorates lupus by up-regulating CD4+CD25+cells and TGF-beta. Proc Natl Acad Sci U S A 103: 8810-8815.
16. Sharabi A, Mozes E, (2008) The suppression of murine lupus by a tolerogenic peptide involves foxp3-expressing CD8 cells that are required for the optimal induction and function of foxp3-expressing CD4 cells. J Immunol 181: 3243-3251.
17. Arazi A, Sharabi A, Zinger H, Mozes E, Neumann AU, (2009) In vivo dynamical interactions between CD4 Tregs, CD8 Tregs and CD4+CD25- cells in mice. PLoS One 4: e8447.
18. Rapoport MJ, Sharabi A, Aharoni D, Bloch O, Zinger H, et al. (2005) Amelioration of SLE-like manifestations in (NZBxNZW)F1 mice following treatment with a peptide based on the complementarity determining region 1 of an autoantibody is associated with a down-regulation of apoptosis and of the pro-apoptotic factor JNK kinase. Clin Immunol 117: 262-270.
19. Sharabi A, Luger D, Ben-David H, Dayan M, Zinger H, et al. (2007) The role of apoptosis in the ameliorating effects of a CDR1-based peptide on lupus manifestations in a mouse model. J Immunol 179: 4979-4987.
20. Parameswaran R, Ben David H, Sharabi A, Zinger H, Mozes E, (2009) B-cell activating factor (BAFF) plays a role in the mechanism of action of a tolerogenic peptide that ameliorates lupus. Clin Immunol 131: 223-232.
21. Lapter S, Ben-David H, Sharabi A, Zinger H, Telerman A, et al. (2011) A role for the B-cell CD74/macrophage migration inhibitory factor pathway in the immunomodulation of systemic lupus erythematosus by a therapeutic tolerogenic peptide. Immunology 132: 87-95.
22. Sela U, Sharabi A, Dayan M, Hershkoviz R, Mozes E, (2009) The role of dendritic cells in the mechanism of action of a peptide that ameliorates lupus in murine models. Immunology 128: e395-405.
23. Sthoeger ZM, Sharabi A, Dayan M, Zinger H, Asher I, et al. (2009) The tolerogenic peptide hCDR1 downregulates pathogenic cytokines and apoptosis and upregulates immunosuppressive molecules and regulatory T cells in peripheral blood mononuclear cells of lupus patients. Hum Immunol 70: 139-145.
24. Sthoeger ZM, Sharabi A, Molad Y, Asher I, Zinger H, et al. (2009) Treatment of lupus patients with a tolerogenic peptide, hCDR1 (Edratide): immunomodulation of gene expression. J Autoimmun 33: 77-82.
25. Lee PY, Reeves WH, (2006) Type I interferon as a target of treatment in SLE. Endocr Metab Immune Disord Drug Targets 6: 323-330.
26. Crow MK, Kirou KA, (2004) Interferon-alpha in systemic lupus erythematosus. Curr Opin Rheumatol 16: 541-547.
27. Ytterberg SR, Schnitzer TJ, (1982) Serum interferon levels in patients with systemic lupus erythematosus. Arthritis Rheum 25: 401-406.
28. Kirou KA, Lee C, George S, Louca K, Peterson MG, et al. (2005) Activation of the interferon-alpha pathway identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease. Arthritis Rheum 52: 1491-1503.
29. Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, et al. (2003) Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A 100: 2610-2615.
30. Santiago-Raber ML, Baccala R, Haraldsson KM, Choubey D, Stewart TA, et al. (2003) Type-I interferon receptor deficiency reduces lupus-like disease in NZB mice. J Exp Med 197: 777-788.
31. Zagury D, Le Buanec H, Mathian A, Larcier P, Burnett R, et al. (2009) IFNalpha kinoid vaccine-induced neutralizing antibodies prevent clinical manifestations in a lupus flare murine model. Proc Natl Acad Sci U S A 106: 5294-5299.
32. Shahin D, El-Refaey AM, El-Hawary AK, Salam AA, Machaly S, et al. (2011) Serum Interferon-alpha level in first degree relatives of systemic lupus erythematosus patients: correlation with autoantibodies titers. The Egyptian J Med Hum Genetics 12: 139-146.
33. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, et al. (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25: 1271-1277.
34. Sela U, Mauermann N, Hershkoviz R, Zinger H, Dayan M, et al. (2005) The inhibition of autoreactive T cell functions by a peptide based on the CDR1 of an anti-DNA autoantibody is via TGF-beta-mediated suppression of LFA-1 and CD44 expression and function. J Immunol 175: 7255-7263.
35. Ben-David H, Sharabi A, Parameswaran R, Zinger H, Mozes E, (2009) A tolerogenic peptide down-regulates mature B cells in bone marrow of lupus-afflicted mice by inhibition of interleukin-7, leading to apoptosis. Immunology 128: 245-252.
36. Sharabi A, Lapter S, Mozes E, (2010) Bcl-xL is required for the development of functional regulatory CD4 cells in lupus-afflicted mice following treatment with a tolerogenic peptide. J Autoimmun 34: 87-95.
37. Sthoeger ZM, Dayan M, Tcherniack A, Green L, Toledo S, et al. (2003) Modulation of autoreactive responses of peripheral blood lymphocytes of patients with systemic lupus erythematosus by peptides based on human and murine anti-DNA autoantibodies. Clin Exp Immunol 131: 385-392.
38. Farkas A, Tonel G, Nestle FO, (2008) Interferon-alpha and viral triggers promote functional maturation of human monocyte-derived dendritic cells. Br J Dermatol 158: 921-929.
39. Gigante M, Mandic M, Wesa AK, Cavalcanti E, Dambrosio M, et al. (2008) Interferon-alpha (IFN-alpha)-conditioned DC preferentially stimulate type-1 and limit Treg-type in vitro T-cell responses from RCC patients. J Immunother 31: 254-262.
40. Yan B, Ye S, Chen G, Kuang M, Shen N, et al. (2008) Dysfunctional CD4+,CD25+regulatory T cells in untreated active systemic lupus erythematosus secondary to interferon-alpha-producing antigen-presenting cells. Arthritis Rheum 58: 801-812.
41. Braun D, Caramalho I, Demengeot J, (2002) IFN-alpha/beta enhances BCR-dependent B cell responses. Int Immunol 14: 411-419.
42. Badr G, Saad H, Waly H, Hassan K, Abdel-Tawab H, et al. (2010) Type I interferon (IFN-alpha/beta) rescues B-lymphocytes from apoptosis via PI3Kdelta/Akt, Rho-A, NFkappaB and Bcl-2/Bcl(XL). Cell Immunol 263: 31-40.
43. Litinskiy MB, Nardelli B, Hilbert DM, He B, Schaffer A, et al. (2002) DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nat Immunol 3: 822-829.
44. Mitani Y, Takaoka A, Kim SH, Kato Y, Yokochi T, et al. (2001) Cross talk of the interferon-alpha/beta signalling complex with gp130 for effective interleukin-6 signalling. Genes Cells 6: 631-640.
45. Sela U, Dayan M, Hershkoviz R, Lider O, Mozes E, (2008) A peptide that ameliorates lupus up-regulates the diminished expression of early growth response factors 2 and 3. J Immunol 180: 1584-1591.
46. Sharabi A, Sthoeger ZM, Mahlab K, Lapter S, Zinger H, et al. (2009) A tolerogenic peptide that induces suppressor of cytokine signaling (SOCS)-1 restores the aberrant control of IFN-gamma signaling in lupus-affected (NZB×NZW)F1 mice. Clin Immunol 133: 61-68.
47. Mauermann N, Sthoeger Z, Zinger H, Mozes E, (2004) Amelioration of lupus manifestations by a peptide based on the complementarity determining region 1 of an autoantibody in severe combined immunodeficient (SCID) mice engrafted with peripheral blood lymphocytes of systemic lupus erythematosus (SLE) patients. Clin Exp Immunol 137: 513-520.
48. Gladman DD, Ibañez D, Urowitz MB, (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29: 288-291.
49. Yee CS, Isenberg DA, Prabu A, Sokoll K, Teh LS, et al. (2008) BILAG-2004 index captures systemic lupus erythematosus disease activity better than SLEDAI-2000. Ann Rheum Dis 67: 873-876.