Linked Life Data

15238091

Source:http://linkedlifedata.com/resource/pubmed/id/15238091

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2004-7-7
pubmed:abstractText
Rituximab (RTX) has proven efficacious in the treatment of rheumatoid arthritis (RA). Herein, we assessed the apoptosis-inducing capability of RTX in vitro on RA peripheral blood B-cell subsets and also compared the effects of RTX on B cells from rheumatoid factor-positive (RF+) and RF- patients. The likely relevance of B cells in disease was assessed by measuring B-cell-modulating serum cytokines. Peripheral blood B cells were isolated and cultured with the presence or absence of RTX. The levels of apoptosis within the naïve, memory and IgD+CD27+ B-cell subpopulations were determined by cytofluorometric analysis and caspase 3/7 assays. Levels of serum cytokines were measured with a multiplex cytokine array system. RTX induced significant apoptosis in all B-cell subsets in both RA and controls. In naïve and memory B cells from RA patients, RTX induced significantly higher levels of apoptosis than in controls. RTX induced apoptosis of B cells in RF+ and RF- patients. Serum levels of interleukin-1beta (IL-1beta), IL-4, IL-10 and IL-13 were profoundly increased in RF+ patients compared to RF- patients and controls. Although our cohort was small (10 RA patients), the data suggest that RTX induces apoptosis in all investigated subsets of B cells from RA patients. Interestingly, memory B cells from RA patients were more sensitive to RTX than memory cells from normal controls, suggesting that the delay in treatment response to RTX observed in clinical trials may be due in part to memory cell depletion. The apoptotic effects of RTX were similar in RF+ and RF- patients, but serum levels of B-cell-activating cytokine levels were only elevated in RF+ but not RF- patients. These data suggest that RTX is less effective in RF- RA because B cells play a less significant role in RA pathogenesis in RF- patients.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0300-9475
pubmed:author
pubmed:issnType
Print
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
209-18
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:articleTitle
Apoptotic effect of rituximab on peripheral blood B cells in rheumatoid arthritis.
pubmed:affiliation
Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Armauer Hansen Building, N-5021 Bergen, Norway. peter.szodoray@gades.uib.no
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't