Anti-CD20 antibody suppresses anti-HLA antibody formation in a HLA-A2 transgenic mouse model of sensitization.
Transpl Immunol
; 19(3-4): 178-86, 2008 Jul.
Article
em En
| MEDLINE
| ID: mdl-18595710
ABSTRACT
BACKGROUND:
B cell depletion by anti-CD20 antibody is used in desensitization protocols and for treatment of antibody-mediated rejection (AMR). However, little is known about the efficacy and the mechanism(s) of action.METHODS:
A mouse model of HLA sensitization was used to study the effectiveness of anti-CD20 treatment on B cell depletion and anti-HLA antibody suppression.RESULTS:
Immunization of C57BL/6 mice with skin grafts from a transgenic C57BL.Tg/HLA-A2.1 mouse resulted in robust production of anti-HLA IgM and IgG antibodies, and accelerated rejection of a secondary skin allograft (within 3 days) featured by intragraft IgG and C4d deposition. Both IgM and IgG alloantibodies are specific to HLA-A2 as well as to a panel of class I HLA, including A1, A3, A25, A26, A29, and A30. These alloantibodies were complement-dependently cytotoxic (CDC) against HLA-A2 expressing target cells. Administration of 2 doses of a mouse-anti-mouse CD20 monoclonal antibody significantly reduced the levels of anti-HLA IgG2a antibodies, suppressed serum CDC, and prolonged survival of the secondary skin allografts. Suppression of anti-HLA IgG antibodies was associated with significant depletion of B220(+)/CD5(-) B cells from the blood, the spleen and the bone marrow of the treated animals.CONCLUSION:
Anti-CD20 treatment effectively depletes B220(+)/CD5(-) B cells, resulting in potent suppression of anti-HLA IgG and prolongation of skin graft survival. The data are in support for the use of anti-CD20 antibodies in highly-HLA sensitized patients undergoing desensitization and for the treatment of AMR.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antígeno HLA-A2
/
Antígenos CD20
/
Rejeição de Enxerto
/
Sobrevivência de Enxerto
/
Anticorpos Monoclonais
/
Formação de Anticorpos
Tipo de estudo:
Guideline
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Transpl Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
TRANSPLANTE
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos