Cytokines BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand) and their role in autoimmune diseases
Authors:
O. Kryštůfková
Authors‘ workplace:
Revmatologický ústav, Praha
Published in:
Čes. Revmatol., 16, 2008, No. 1, p. 9-15.
Category:
Overview Reports
Overview
B-lymphocytes play a significant role in pathogenesis of autoimmune diseases, and they are the target cells in therapy of resistant forms of connective tissue diseases (CTD). Cytokine BAFF (B-cell activating factor) supports maturation and survival of various differentiation stages of B-lymphocytes including autoreactive clones. The functions of BAFF are complex, since it has three receptors, two of which are shared with another ligand called APRIL (a proliferation-inducing ligand). These are BAFF-R (BAFF receptor), BCMA (B-cell maturation antigen) and TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor), and are differentially expressed in various stages of B-cells maturation. The fact that high levels of cytokines BAFF and APRIL in serum and expression in affected organs have been found in patients with various connective tissue diseases, such as primary Sjögren syndrome, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis or dermatomyositis/polymyositis indicates biological significance of these cytokines in pathogenesis of CTD. Abnormal levels of BAFF have correlated with the activity of disease or with the positivity of autoantibodies or their titer. Based on these findings and experience with neutralization of BAFF by means of antibodies or receptors in mice models of autoimmune diseases, this cytokine has become potential therapeutic target. The block of BAFF can be preferable to induction of B-lymphocytes depletion by antibodies against the molecule CD20 (e.g. rituximab), which can not be found on the surface of all differentiation stages of B-lymphocytes. It has been found out, that rituximab therapy leads to elevation of BAFF levels in serum, what could lead to proliferation of autoreactive clones in the course of B-cells repopulation. At the present time, the monoclonal antibody against BAFF – belimumab and recombinant receptor TACI fused Ig - atacicept and BAFF-R-Ig (BR3-Fc) are successfully being studied in clinical trials.
Key words:
BAFF, APRIL, BAFF receptor, BCMA, TACI, systemic rheumatic diseases
Sources
1. Mackay F, Woodcock SA, Lawton P, et al. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med 1999; 190: 1697–1710.
2. Mackay F, Schneider P, Rennert P, Browning J. BAFF AND APRIL: a tutorial on B cell survival. Annu Rev Immunol 2003; 21: 231–264.
3. Bodmer JL, Schneider P,Tschopp J. The molecular architecture of the TNF superfamily. Trends Biochem Sci 2002; 27: 19–26.
4. Lopez-Fraga M, Fernandez R, Albar JP, Hahne M. Biologically active APRIL is secreted following intracellular processing in the Golgi apparatus by furin convertase. EMBO Rep 2001; 2: 945–951.
5. Gavin AL, Ait-Azzouzene D, Ware CF, Nemazee D. DeltaBAFF, an alternate splice isoform that regulates receptor binding and biopresentation of the B cell survival cytokine, BAFF. J Biol Chem 2003; 278: 38220–38228.
6. Roschke V, Sosnovtseva S, Ward CD, et al. BLyS and APRIL form biologically active heterotrimers that are expressed in patients with systemic immune-based rheumatic diseases. J Immunol 2002; 169: 4314–4321.
7. Pradet-Balade B, Medema JP, Lopez-Fraga M, et al. An endogenous hybrid mRNA encodes TWE-PRIL, a functional cell surface TWEAK-APRIL fusion protein. Embo J 2002; 21: 5711–5720.
8. Hahne M, Kataoka T, Schroter M, et al. APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth. J Exp Med 1998; 188: 1185–1190.
9. Litinskiy MB, Nardelli B, Hilbert DM, et al. DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nat Immunol 2002; 3: 822–829
10. Nardelli B, Belvedere O, Roschke V, et al. Synthesis and release of B-lymphocyte stimulator from myeloid cells. Blood 2001; 97: 198–204.
11. Munoz-Fernandez R, Blanco FJ, Frecha C, et al. Follicular dendritic cells are related to bone marrow stromal cell progenitors and to myofibroblasts. J Immunol 2006; 177: 280–289.
12. Kato A, Truong-Tran AQ, Scott AL, Matsumoto K, Schleimer RP. Airway epithelial cells produce B cell-activating factor of TNF family by an IFN-beta-dependent mechanism. J Immunol 2006; 177: 7164–7172.
13. Ittah M, Miceli-Richard C, Eric Gottenberg J, et al. B cell-activating factor of the tumor necrosis factor family (BAFF) is expressed under stimulation by interferon in salivary gland epithelial cells in primary Sjogren’s syndrome. Arthritis Res Ther 2006; 8: R51.
14. Ohata J, Zvaifler NJ, Nishio M, et al. Fibroblast-like synoviocytes of mesenchymal origin express functional B cell-activating factor of the TNF family in response to proinflammatory cytokines. J Immunol 2005; 174: 864–870.
15. Krumbholz M, Theil D, Derfuss T, et al. BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma. J Exp Med 2005; 201: 195–200.
16. Schaumann DH, Tuischer J, Ebell W, Manz RA, Lauster R. VCAM-1-positive stromal cells from human bone marrow producing cytokines for B lineage progenitors and for plasma cells: SDF-1, flt3L, and BAFF. Mol Immunol 2007; 44: 1606–1612.
17. Abe M, Kido S, Hiasa M, et al. BAFF and APRIL as osteoclast-derived survival factors for myeloma cells: a rationale for TACI-Fc treatment in patients with multiple myeloma. Leukemia 2006; 20: 1313-1315.
18. Mackay F, Sierro F, Grey ST,Gordon TP. The BAFF/APRIL system: an important player in systemic rheumatic diseases. Curr Dir Autoimmun 2005; 8: 243–265.
19. Moon EY, Lee JH, Oh SY, et al. Reactive oxygen species augment B-cell-activating factor expression. Free Radic Biol Med 2006; 40: 2103–2111.
20. Avery DT, Kalled SL, Ellyard JI, et al. BAFF selectively enhances the survival of plasmablasts generated from human memory B cells. J Clin Invest 2003; 112: 286–297.
21. O’Connor BP, Raman VS, Erickson LD, et al. BCMA is essential for the survival of long-lived bone marrow plasma cells. J Exp Med 2004; 199: 91–98.
22. Klein B, Tarte K, Jourdan M, et al. Survival and proliferation factors of normal and malignant plasma cells. Int J Hematol 2003; 78: 106–113.
23. Ng LG, Sutherland AP, Newton R, et al. B cell-activating factor belonging to the TNF family (BAFF)-R is the principal BAFF receptor facilitating BAFF costimulation of circulating T and B cells. J Immunol 2004; 173: 807–817.
24. Chang SK, Arendt BK, Darce JR, Wu X, Jelinek DF. A role for BLyS in the activation of innate immune cells. Blood 2006; 108: 2687–2694.
25. Mackay F, Leung H. The role of the BAFF/APRIL system on T cell function. Semin Immunol 2006; 18: 284–289.
26. Schneider P. The role of APRIL and BAFF in lymphocyte activation. Curr Opin Immunol 2005; 17: 282–289.
27. Thien M, Phan TG, Gardam S, et al. Excess BAFF rescues self-reactive B cells from peripheral deletion and allows them to enter forbidden follicular and marginal zone niches. Immunity 2004; 20: 785–798.
28. Kalled SL, Ambrose C,Hsu YM. The biochemistry and biology of BAFF, APRIL and their receptors. Curr Dir Autoimmun 2005; 8: 206–242.
29. Castigli E,Geha RS. TACI, isotype switching, CVID and IgAD. Immunol Res 2007; 38: 102–111.
30. Gross JA, Johnston J, Mudri S, et al. TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature 2000; 404: 995–999.
31. Zhang M, Ko KH, Lam QL, et al. Expression and function of TNF family member B cell-activating factor in the development of autoimmune arthritis. Int Immunol 2005; 17: 1081–1092.
32. Stohl W. BlySfulness does not equal blissfulness in systemic lupus erythematosus: a therapeutic role for BLyS antagonists. Curr Dir Autoimmun 2005; 8: 289–304.
33. Pers JO, Daridon C, Devauchelle V, et al. BAFF overexpression is associated with autoantibody production in autoimmune diseases. Ann N Y Acad Sci 2005; 1050: 34–39.
34. Schaller M, Stohl W, Tan SM, et al. Raised levels of anti-glucose-6-phosphate isomerase IgG in serum and synovial fluid from patients with inflammatory arthritis. Ann Rheum Dis 2005; 64: 743–749.
35. Matsushita T, Hasegawa M, Matsushita Y, et al. Elevated serum BAFF levels in patients with localized scleroderma in contrast to other organ-specific autoimmune diseases. Exp Dermatol 2007; 16: 87–93.
36. Matsushita T, Hasegawa M, Yanaba K, et al. Elevated serum BAFF levels in patients with systemic sclerosis: enhanced BAFF signaling in systemic sclerosis B lymphocytes. Arthritis Rheum 2006; 54: 192–201.
37. Thangarajh M, Masterman T, Hillert J, Moerk S, Jonsson R. A proliferation-inducing ligand (APRIL) is expressed by astrocytes and is increased in multiple sclerosis. Scand J Immunol 2007; 65: 92–98.
38. Thangarajh M, Masterman T, Rot U, et al. Increased levels of APRIL (a proliferation-inducing ligand) mRNA in multiple sclerosis. J Neuroimmunol 2005; 167: 210–214
39. Krumbholz M, Specks U, Wick M, et al. BAFF is elevated in serum of patients with Wegener’s granulomatosis. J Autoimmun 2005; 25: 298–302.
40. Asashima N, Fujimoto M, Watanabe R, et al. Serum levels of BAFF are increased in bullous pemphigoid but not in pemphigus vulgaris. Br J Dermatol 2006; 155: 330–336.
41. Thangarajh M, Masterman T, Helgeland L, et al. The thymus is a source of B-cell-survival factors-APRIL and BAFF-in myasthenia gravis. J Neuroimmunol 2006; 178: 161–166.
42. Cheema GS, Roschke V, Hilbert DM, Stohl W. Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases. Arthritis Rheum 2001; 44: 1313–1319.
43. Stohl W, Metyas S, Tan SM, et al. B lymphocyte stimulator overexpression in patients with systemic lupus erythematosus: longitudinal observations. Arthritis Rheum 2003; 48: 3475–3486.
44. Jiang Y, Ohtsuji M, Abe M, et al. Polymorphism and chromosomal mapping of the mouse gene for B-cell activating factor belonging to the tumor necrosis factor family (Baff) and association with the autoimmune phenotype. Immunogenetics 2001; 53: 810–813.
45. Kawasaki A, Tsuchiya N, Fukazawa T, Hashimoto H,Tokunaga K. Analysis on the association of human BLYS (BAFF, TNFSF13B) polymorphisms with systemic lupus erythematosus and rheumatoid arthritis. Genes Immun 2002; 3: 424–429.
46. Koyama T, Tsukamoto H, Masumoto K, et al. A novel polymorphism of the human APRIL gene is associated with systemic lupus erythematosus. Rheumatology (Oxford) 2003; 42: 980–985.
47. Wenzel J, Schmidt R, Proelss J, et al. Type I interferon-associated skin recruitment of CXCR3+ lymphocytes in dermatomyositis. Clin Exp Dermatol 2006; 31: 576–582.
48. Eloranta M-L, Barbasso Helmers S, Ulfgren A-K, et al. A possible mechanism for endogenous activation of the type I interferon system in myositis patients with anti–Jo-1 or anti–Ro52/Anti–Ro60 autoantibodies. Arthritis Rheum 2007; 56: 3112-24.
49. Greenberg SA, Pinkus JL, Pinkus GS, et al. Interferon-alpha/beta-mediated innate immune mechanisms in dermatomyositis. Ann Neurol 2005; 57: 664–678.
50. Greenberg SA, Pinkus GS, Amato AA, Pinkus JL. Myeloid dendritic cells in inclusion-body myositis and polymyositis. Muscle Nerve 2007; 35: 17–23.
51. Ramanujam M, Davidson A. The current status of targeting BAFF/BLyS for autoimmune diseases. Arthritis Res Ther 2004; 6: 197–202.
52. Sutherland AP, Mackay F,Mackay CR. Targeting BAFF: immunomodulation for autoimmune diseases and lymphomas. Pharmacol Ther 2006; 112: 774–786.
53. Vallerskog T, Heimburger M, Gunnarsson I, et al. Differential effects on BAFF and APRIL levels in rituximab-treated patients with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Res Ther 2006; 8: R167.
54. Lavie F, Miceli-Richard C, Ittah M, et al. Increase of B cell-activating factor of the TNF family (BAFF) after rituximab treatment: insights into a new regulating system of BAFF production. Ann Rheum Dis 2007; 66: 700–703.
55. Baker KP, Edwards BM, Main SH, et al. Generation and characterization of LymphoStat-B, a human monoclonal antibody that antagonizes the bioactivities of B lymphocyte stimulator. Arthritis Rheum 2003; 48: 3253–3265.
56. Pelletier M, Thompson JS, Qian F, et al. Comparison of soluble decoy IgG fusion proteins of BAFF-R and BCMA as antagonists for BAFF. J Biol Chem 2003; 278: 33127–33133.
57. Gross JA, Dillon SR, Mudri S, et al. TACI-Ig neutralizes molecules critical for B cell development and autoimmune disease. impaired B cell maturation in mice lacking BLyS. Immunity 2001; 15: 289–302.
58. Patel DR, Wallweber HJ, Yin J, et al. Engineering an APRIL-specific B cell maturation antigen. J Biol Chem 2004; 279: 16727–16735.
59. Kayagaki N, Yan M, Seshasayee D, et al. BAFF/BLyS receptor 3 binds the B cell survival factor BAFF ligand through a discrete surface loop and promotes processing of NF-kappaB2. Immunity 2002; 17: 515–524.
60. Mackay F, Silveira PA,Brink R. B cells and the BAFF/APRIL axis: fast-forward on autoimmunity and signaling. Curr Opin Immunol 2007; 19: 327–336.
61. Dillon SR, Gross JA, Ansell SM, Novak AJ. An APRIL to remember: novel TNF ligands as therapeutic targets. Nat Rev Drug Discov 2006; 5: 235–246.
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