An antibody-based construct carrying DNA-mimotope and targeting CR1(CD35) selectively suppresses human autoreactive B-lymphocytes

被引:27
作者
Voynova, Elisaveta [1 ]
Tchorbanov, Andrey [1 ]
Prechl, Jozsef [2 ]
Nikolova, Milena [3 ]
Baleva, Marta [4 ]
Erdei, Anna [2 ,5 ]
Vassilev, Tchavdar [1 ]
机构
[1] Bulgarian Acad Sci, Inst Microbiol, Dept Immunol, BG-1040 Sofia, Bulgaria
[2] Eotvos Lorand Univ, Dept Immunol, Budapest, Hungary
[3] Med Univ Sofia, Univ Hosp Alexandrovska, Dept Nephrol, Sofia, Bulgaria
[4] Med Univ Sofia, Univ Hosp Alexandrovska, Dept Allergol, Sofia, Bulgaria
[5] Eotvos Lorand Univ, Hungarian Acad Sci, Dept Immunol, Res Grp, Budapest, Hungary
关键词
inhibitory B cell receptors; complement receptor 1 (CD35); SLE;
D O I
10.1016/j.imlet.2007.12.016
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
There is an urgent and unmet need for therapeutic agents targeting selectively disease-associated B-lymphocytes in autoantibody-mediated diseases. We have constructed a chimeric molecule able to cross-link cell surface immunoglobulin with the inhibitory complement receptor type 1 (CD35) on DNA-specific B cells from SLE (systemic lupus erythematosus) patients with the aim of selectively silencing them. This engineered molecule is made of copies of the DNA-mimotope peptide DWEYSVWLSN coupled to a monoclonal anti-CD35 antibody. We found that the DNA-like peptide chimera induced a dose-dependent decrease in the number of IgG anti-dsDNA antibody producing cells when PBMCs of lupus patients were cultured in its presence. Our data present evidence that clustering BCR and the inhibitory CRI on disease-associated autoreactive B-lymphocytes selectively suppresses autoantibody production. (C) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:168 / 173
页数:6
相关论文
共 22 条
[1]   Delayed memory B cell recovery in peripheral blood and lymphoid tissue in systemic lupus erythematosus after B cell depletion therapy [J].
Anolik, Jennifer H. ;
Barnard, Jennifer ;
Owen, Teresa ;
Zheng, Bo ;
Kemshetti, Sunil ;
Looney, R. John ;
Sanz, Inaki .
ARTHRITIS AND RHEUMATISM, 2007, 56 (09) :3044-3056
[2]   Rituximab improves peripheral B cell abnormalities in human systemic lupus erythematosus [J].
Anolik, JH ;
Barnard, J ;
Cappione, A ;
Pugh-Bernard, AE ;
Felgar, RE ;
Looney, RJ ;
Sanz, I .
ARTHRITIS AND RHEUMATISM, 2004, 50 (11) :3580-3590
[3]   A novel mouse with B cells but lacking serum antibody reveals an antibody-independent role for B cells in murine lupus [J].
Chan, OTM ;
Hannum, LG ;
Haberman, AM ;
Madaio, MP ;
Shlomchik, MJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (10) :1639-1647
[4]   Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for immunotherapy of systemic lupus erythematosus [J].
Doerner, Thomas ;
Kaufmann, Joerg ;
Wegener, William A. ;
Teoh, Nick ;
Goldenberg, David M. ;
Burmester, Gerd R. .
ARTHRITIS RESEARCH & THERAPY, 2006, 8 (03)
[5]   The therapeutic potential of anti-CD20 - What do B-cells do? [J].
Eisenberg, R ;
Looney, RJ .
CLINICAL IMMUNOLOGY, 2005, 117 (03) :207-213
[6]  
ERDEI A, 1994, MED INTELL UNIT
[7]   First clinical trials of a new heteropolymer technology agent in normal healthy volunteers and patients with systemic lupus erythematosus: safety and proof of principle of the antigen-heteropolymer ETI-104 [J].
Iking-Konert, C ;
Stocks, S ;
Weinsberg, F ;
Engelbrecht, R ;
Bleck, E ;
Perniok, A ;
Fischer-Betz, R ;
Pincus, S ;
Nardone, L ;
Schneider, M .
ANNALS OF THE RHEUMATIC DISEASES, 2004, 63 (09) :1104-1112
[8]   Differential effects of epratuzumab on peripheral blood B cells of patients with systemic lupus erythematosus versus normal controls [J].
Jacobi, A. M. ;
Goldenberg, D. M. ;
Hiepe, F. ;
Radbruch, A. ;
Burmester, G. R. ;
Doerner, T. .
ANNALS OF THE RHEUMATIC DISEASES, 2008, 67 (04) :450-457
[9]   Complement receptor type 1 (CD35) mediates inhibitory signals in human B lymphocytes [J].
Józsi, M ;
Prechl, J ;
Bajtay, Z ;
Erdei, A .
JOURNAL OF IMMUNOLOGY, 2002, 168 (06) :2782-2788
[10]   Naturally processed chromatin peptides reveal a major autoepitope that primes pathogenic T and B cells of lupus [J].
Kaliyaperumal, A ;
Michaels, MA ;
Datta, SK .
JOURNAL OF IMMUNOLOGY, 2002, 168 (05) :2530-2537