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01-06-2003 | Commentary

SLE - Systemic lupus erythematosus: a BLySful, yet BAFFling, disorder

Author: William Stohl, MD, PhD

Published in: Arthritis Research & Therapy | Issue 3/2003

Abstract

BLyS/BAFF (B-lymphocyte stimulator/B-cell activating factor) is a vital B-cell survival factor. Overexpression of BLyS in mice may lead to systemic-lupus-erythematosus-like (SLE-like) disease, and BLyS overexpression is common in human SLE. Treatment of SLE-prone mice with a BLyS antagonist ameliorates disease progression and enhances survival, making BLyS an attractive therapeutic target in human disease. However, several unresolved issues remain, including what is the contributory role of APRIL (a tumor-necrosis-factor superfamily member related to BLyS) in the 'autoimmunogenic' effects of BLyS, identification of the 'optimal' BLyS antagonist, and identification of those SLE patients most likely to benefit from BLyS antagonist therapy.

Moore PA, Belvedere O, Orr A, Pieri K, LaFleur DW, Feng P, Soppet D, Charters M, Gentz R, Parmelee D, Li Y, Galperina O, Giri J, Roschke V, Nardelli B, Carrell J, Sosnovtseva S, Greenfield W, Ruben SM, Olsen HS, Fikes J, Hilbert DM: BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science. 1999, 285: 260-263. 10.1126/science.285.5425.260.CrossRefPubMed

Shu H-B, Hu W-H, Johnson H: TALL-1 is a novel member of the TNF family that is down-regulated by mitogens. J Leukocyte Biol. 1999, 65: 680-683.PubMed

Schneider P, MacKay F, Steiner V, Hofmann K, Bodmer J-L, Holler N, Ambrose C, Lawton P, Bixler S, Acha-Orbea H, Valmori D, Romero P, Werner-Favre C, Zubler RH, Browning JL, Tschopp J: BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J Exp Med. 1999, 189: 1747-1756. 10.1084/jem.189.11.1747.PubMedCentralCrossRefPubMed

Mukhopadhyay A, Ni J, Zhai Y, Yu G-L, Aggarwal BB: Identification and characterization of a novel cytokine, THANK, a TNF homologue that activates apoptosis, nuclear factor-κB, and c-Jun NH₂-terminal kinase. J Biol Chem. 1999, 274: 15978-15981. 10.1074/jbc.274.23.15978.CrossRefPubMed

Gross JA, Johnston J, Mudri S, Enselman R, Dillon SR, Madden K, Xu W, Parrish-Novak J, Foster D, Lofton-Day C, Moore M, Littau A, Grossman A, Haugen H, Foley K, Blumberg H, Harrison K, Kindsvogel W, Clegg CH: TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature. 2000, 404: 995-999. 10.1038/35010115.CrossRefPubMed

Thompson JS, Schneider P, Kalled SL, Wang L, Lefevre EA, Cachero TG, MacKay F, Bixler SA, Zafari M, Liu Z-Y, Woodcock SA, Qian F, Batten M, Madry C, Richard Y, Benjamin CD, Browning JL, Tsapis A, Tschopp J, Ambrose C: BAFF binds to the tumor necrosis factor receptor-like molecule B cell maturation antigen and is important for maintaining the peripheral B cell population. J Exp Med. 2000, 192: 129-135. 10.1084/jem.192.1.129.PubMedCentralCrossRefPubMed

Do RKG, Hatada E, Lee H, Tourigny MR, Hilbert D, Chen-Kiang S: Attenuation of apoptosis underlies B lymphocyte stimulator enhancement of humoral immune response. J Exp Med. 2000, 192: 953-964. 10.1084/jem.192.7.953.PubMedCentralCrossRefPubMed

Batten M, Groom J, Cachero TG, Qian F, Schneider P, Tschopp J, Browning JL, Mackay F: mediates survival of peripheral immature B lymphocytes. J Exp Med. 2000, 192: 1453-1465. 10.1084/jem.192.10.1453.PubMedCentralCrossRefPubMed

Gross JA, Dillon SR, Mudri S, Johnston J, Littau A, Roque R, Rixon M, Schou O, Foley KP, Haugen H, McMillen S, Waggie K, Schreckhise RW, Shoemaker K, Vu T, Moore M, Grossman A, Clegg CH: 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. 10.1016/S1074-7613(01)00183-2.CrossRefPubMed

10.

Schiemann B, Gommerman JL, Vora K, Cachero TG, Shulga-Morskaya S, Dobles M, Frew E, Scott ML: An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway. Science. 2001, 293: 2111-2114. 10.1126/science.1061964.CrossRefPubMed

11.

Mackay F, Woodcock SA, Lawton P, Ambrose C, Baetscher M, Schneider P, Tschopp J, Browning JL: Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med. 1999, 190: 1697-1710. 10.1084/jem.190.11.1697.PubMedCentralCrossRefPubMed

12.

Khare SD, Sarosi I, Xia X-Z, McCabe S, Miner K, Solovyev I, Hawkins N, Kelley M, Chang D, Van G, Ross L, Delaney J, Wang L, Lacey D, Boyle WJ, Hsu H: Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice. Proc Natl Acad Sci USA. 2000, 97: 3370-3375. 10.1073/pnas.050580697.PubMedCentralCrossRefPubMed

13.

Zhang J, Roschke V, Baker KP, Wang Z, Alarcón GS, Fessler BJ, Bastian H, Kimberly RP, Zhou T: Cutting edge: a role for B lymphocyte stimulator in systemic lupus erythematosus. J Immunol. 2001, 166: 6-10.CrossRefPubMed

14.

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. 10.1002/1529-0131(200106)44:6<1313::AID-ART223>3.0.CO;2-S.CrossRefPubMed

15.

Groom J, Kalled SL, Cutler AH, Olson C, Woodcock SA, Schneider P, Tschopp J, Cachero TG, Batten M, Wheway J, Mauri D, Cavill D, Gordon TP, Mackay CR, Mackay F: Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjögren's syndrome. J Clin Invest. 2002, 109: 59-68. 10.1172/JCI200214121.PubMedCentralCrossRefPubMed

16.

Stohl W, Cheema GS, Briggs W, Xu D, Sosnovtseva S, Roschke V, Ferrara DE, Labat K, Sattler FR, Pierangeli SS, Hilbert DM: B lymphocyte stimulator protein-associated increase in circulating autoantibody levels may require CD4⁺ T cells: lessons from HIV-infected patients. Clin Immunol. 2002, 104: 115-122. 10.1006/clim.2002.5238.CrossRefPubMed

17.

Kayagaki N, Yan M, Seshasayee D, Wang H, Lee W, French DM, Grewal IS, Cochran AG, Gordon NC, Yin J, Starovasnik MA, Dixit VM: BAFF/BLyS receptor 3 binds the B cell survival factor BAFF ligand through a discrete surface loop and promotes processing of NF-κB2. Immunity. 2002, 10: 515-524. 10.1016/S1074-7613(02)00425-9.CrossRef

18.

Thompson JS, Bixler SA, Qian F, Vora K, Scott ML, Cachero TG, Hession C, Schneider P, Sizing ID, Mullen C, Strauch K, Zafari M, Benjamin CD, Tschopp J, Browning JL, Ambrose C: BAFF-R, a novel TNF receptor that specifically interacts with BAFF. Science. 2001, 293: 2108-2111. 10.1126/science.1061965.CrossRefPubMed

19.

Yan M, Brady JR, Chan B, Lee WP, Hsu B, Harless S, Cancro M, Grewal IS, Dixit VM: Identification of a novel receptor for B lymphocyte stimulator that is mutated in a mouse strain with severe B cell deficiency. Curr Biol. 2001, 11: 1547-1552. 10.1016/S0960-9822(01)00481-X.CrossRefPubMed

20.

Marsters SA, Yan M, Pitti RM, Haas PE, Dixit VM, Ashkenazi A: Interaction of the TNF homologues BLyS and APRIL with the receptor homologues BCMA and TACI. Curr Biol. 2000, 10: 785-788. 10.1016/S0960-9822(00)00566-2.CrossRefPubMed

21.

Yu G, Boone T, Delaney J, Hawkins N, Kelley M, Ramakrishnan M, McCabe S, Qiu W-r, Kornuc M, Xia X-Z, Guo J, Stolina M, Boyle WJ, Sarosi K, Hsu H, Senaldi G, Theill LE: APRIL and TALL-1 and receptors BCMA and TACI: system for regulating humoral immunity. Nat Immunol. 2000, 1: 252-256. 10.1038/79802.CrossRefPubMed

22.

Wu Y, Bressette D, Carrell JA, Kaufman T, Feng P, Taylor K, Gan Y, Cho YH, Garcia AD, Gollatz E, Dimke D, LaFleur D, Migone TS, Nardelli B, Wei P, Ruben SM, Ullrich SJ, Olsen HS, Kanakaraj P, Moore PA, Baker KP: Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS. J Biol Chem. 2000, 275: 35478-35485. 10.1074/jbc.M005224200.CrossRefPubMed

23.

Rennert P, Schneider P, Cachero TG, Thompson J, Trabach L, Hertig S, Holler N, Qian F, Mullen C, Strauch K, Browning JL, Ambrose C, Tschopp J: A soluble form of B cell maturation antigen, a receptor for the tumor necrosis factor family member APRIL, inhibits tumor cell growth. J Exp Med. 2000, 192: 1677-1683. 10.1084/jem.192.11.1677.PubMedCentralCrossRefPubMed

24.

Stein JV, López-Fraga M, Elustondo FA, Carvalho-Pinto CE, Rodríguez D, Gómez-Caro R, de Jong J, Martínez-A C, Medema JP, Hahne M: APRIL modulates B and T cell immunity. J Clin Invest. 2002, 109: 1587-1598. 10.1172/JCI200215034.PubMedCentralCrossRefPubMed

25.

Roschke V, Sosnovtseva S, Ward CD, Hong JS, Smith R, Albert V, Stohl W, Baker KP, Ullrich S, Nardelli B, Hilbert DM, Migone TS: BLyS and APRIL form biologically active heterotrimers that are expressed in patients with systemic immune-based rheumatic diseases. J Immunol. 2002, 169: 4314-4321.CrossRefPubMed

Title: SLE - Systemic lupus erythematosus: a BLySful, yet BAFFling, disorder
Author: William Stohl, MD, PhD
Publication date: 01-06-2003
Publisher: BioMed Central
Published in: Arthritis Research & Therapy / Issue 3/2003
Electronic ISSN: 1478-6362
DOI: https://doi.org/10.1186/ar755

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