Modulation of Anti-Tumor Necrosis Factor Alpha (TNF-α) Antibody Secretion in Mice Immunized with TNF-α Kinoid

被引:13
作者
Assier, Eric [1 ]
Semerano, Luca [1 ,2 ]
Duvallet, Emilie [1 ]
Delavallee, Laure [1 ]
Bernier, Emilie [3 ]
Laborie, Marion [3 ]
Grouard-Vogel, Geraldine [3 ]
Larcier, Patrick [3 ]
Bessis, Natacha [1 ]
Boissier, Marie-Christophe [1 ,2 ]
机构
[1] Cite Univ Paris, Bobigny, France
[2] Grp Hosp Avicenne Jean Verdier Rene Muret, AP HP, Serv Rhumatol, Bobigny, France
[3] Neovacs SA, Paris, France
关键词
RHEUMATOID-ARTHRITIS; CELL; METHOTREXATE; VACCINATION; MODEL; INHIBITION; INFLIXIMAB; THERAPY; AGENTS;
D O I
10.1128/CVI.05649-11
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Tumor necrosis factor alpha (TNF-alpha) blockade is an effective treatment for patients with TNF-alpha-dependent chronic inflammatory diseases, such as rheumatoid arthritis, Crohn's disease, and psoriasis. TNF-alpha kinoid, a heterocomplex of human TNF-alpha and keyhole limpet hemocyanin (KLH) (TNF-K), is an active immunotherapy targeting TNF-alpha. Since the TNF-K approach is an active immunization, and patients receiving this therapy also receive immunosuppressant treatment, we evaluated the effect of some immunosuppressive drugs on the generation of anti-TNF-alpha antibodies produced during TNF-K treatment. BALB/c mice were injected intramuscularly with TNF-K in ISA 51 adjuvant. Mice were also injected intraperitoneally with one of the following: phosphate-buffered saline, cyclophosphamide, methylprednisolone, or methotrexate. Anti-TNF-alpha and anti-KLH antibody levels were assessed by enzyme-linked immunosorbent assay and the anti-TNF-alpha neutralizing capacity of sera by L929 bioassay. Our results showed that current treatments used in rheumatoid arthritis, such as methylprednisolone and methotrexate, do not significantly alter anti-TNF-alpha antibody production after TNF-K immunization. In contrast, the administration of cyclophosphamide (200 mg/kg) after immunization significantly reduced anti-TNF-alpha antibody titers and their neutralizing capacity.
引用
收藏
页码:699 / 703
页数:5
相关论文
共 30 条
[11]   Proteasome inhibition for antibody-mediated rejection [J].
Everly, Jason J. ;
Walsh, R. Carlin ;
Alloway, Rita R. ;
Woodle, E. Steve .
CURRENT OPINION IN ORGAN TRANSPLANTATION, 2009, 14 (06) :662-666
[12]   Design of effective immunotherapy for human autoimmunity [J].
Feldmann, M ;
Steinman, L .
NATURE, 2005, 435 (7042) :612-619
[13]   COMPARISON OF INVITRO-CELL CYTO-TOXIC ASSAYS FOR TUMOR NECROSIS FACTOR [J].
FLICK, DA ;
GIFFORD, GE .
JOURNAL OF IMMUNOLOGICAL METHODS, 1984, 68 (1-2) :167-175
[14]  
Furst DE, 2010, CLIN EXP RHEUMATOL, V28, pS5
[15]   The benefit/risk profile of TNF-blocking agents: Findings of a consensus panel [J].
Hochberg, MC ;
Lebwohl, MG ;
Plevy, SE ;
Hobbs, KF ;
Yocum, DE .
SEMINARS IN ARTHRITIS AND RHEUMATISM, 2005, 34 (06) :819-836
[16]   Clinical application and evaluation of anti-TNF-alpha agents for the treatment of rheumatoid arthritis [J].
Jin, Juan ;
Chang, Yan ;
Wei, Wei .
ACTA PHARMACOLOGICA SINICA, 2010, 31 (09) :1133-1140
[17]   Influenza vaccination as model for testing immune modulation induced by anti-TNF and methotrexate therapy in rheumatoid arthritis patients [J].
Kapetanovic, M. C. ;
Saxne, T. ;
Nilsson, J. -A. ;
Geborek, P. .
RHEUMATOLOGY, 2007, 46 (04) :608-611
[18]   Influence of methotrexate, TNF blockers and prednisolone on antibody responses to pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis [J].
Kapetanovic, MC ;
Saxne, T ;
Sjöholm, A ;
Truedsson, L ;
Jönsson, G ;
Geborek, P .
RHEUMATOLOGY, 2006, 45 (01) :106-111
[19]   TRANSGENIC MICE EXPRESSING HUMAN TUMOR-NECROSIS-FACTOR - A PREDICTIVE GENETIC MODEL OF ARTHRITIS [J].
KEFFER, J ;
PROBERT, L ;
CAZLARIS, H ;
GEORGOPOULOS, S ;
KASLARIS, E ;
KIOUSSIS, D ;
KOLLIAS, G .
EMBO JOURNAL, 1991, 10 (13) :4025-4031
[20]   TNFα kinoid vaccination-induced neutralizing antibodies to TNFα protect mice from autologous TNFα-driven chronic and acute inflammation [J].
Le Buanec, Helene ;
Delavallee, Laure ;
Bessis, Natacha ;
Paturance, Sebastien ;
Bizzini, Bernard ;
Gallo, Robert ;
Zagury, Daniel ;
Boissier, Marie-Christophe .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (51) :19442-19447