Altered Toll-like receptor 9 responses in circulating B cells at the onset of extensive chronic graft-versus-host disease.
Biol Blood Marrow Transplant
; 13(4): 386-97, 2007 Apr.
Article
em En
| MEDLINE
| ID: mdl-17382246
ABSTRACT
B cells appear to play a role in chronic graft-versus-host disease (cGVHD) as shown in murine models and the success of anti-CD20 B cell antibody treatment in humans. Recent studies have shown that immunostimulatory microbial CpG-DNA splenic responses were enhanced in murine GVHD. We hypothesized that CpG-induced B cell responses are increased in human cGVHD. Newly diagnosed cGVHD patients enrolled on the COG protocol ASCT0031 were divided into early (3-8 months postblood and marrow transplant [BMT]) and late (> or =9 months post-BMT) onset groups and compared to time-matched control BMT patients. A significantly greater percentage of phosphorothioate (PS)-modified CpG stimulated B cells from cGVHD patients demonstrated an increased expression of CD86 compared to controls (P = .0004). This response had a significant correlation between B cell TLR9 expression (r(2) = 0.65; P = .002) and CD86 upregulation using the entirely TLR9-dependent native phosphodiester CpG (P = .003). The PS-modified CpG response at 2 months after initiation of cGVHD therapy demonstrated a trend toward predicting therapeutic response at 9 months post-BMT (P = .07). These findings suggest that an increased number of B cells, primed for a TLR9 response, may play a role in the pathophysiology of cGVHD.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
/
Transplante de Células-Tronco Hematopoéticas
/
Ilhas de CpG
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Receptor Toll-Like 9
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Doença Enxerto-Hospedeiro
Tipo de estudo:
Guideline
/
Prognostic_studies
Limite:
Adolescent
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Child
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Child, preschool
/
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article