Document Detail

Patients with active inflammatory bowel disease lack immature peripheral blood plasmacytoid and myeloid dendritic cells.
MedLine Citation:
PMID:  15647187     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Breakdown of tolerance against the commensal microflora is believed to be a major factor in the pathogenesis of inflammatory bowel disease (IBD). Dendritic cells (DC) have been implicated in this process in various animal models, but data on human DC in IBD are very limited. AIM: To characterise plasmacytoid DC (PDC) and myeloid DC (MDC) in patients with active versus inactive IBD and healthy controls. PATIENTS AND METHODS: Peripheral blood was obtained from 106 patients (Crohn's disease (CD) n=49, ulcerative colitis (UC) n=57) and healthy controls (n=19). Disease activity was scored using the modified Truelove Witts (MTWSI) for UC and the Harvey Bradshaw severity indices (HBSI) for CD. Four colour flow cytometric analysis was used to identify, enumerate, and phenotype DC. DC from patients with acute flare ups and healthy controls were cultured and stimulated with CpG ODN 2006 or lipopolysaccharide (LPS). RESULTS: IBD patients in remission (PDC UC, 0.39%; CD, 0.35%; MDC-1 UC, 0.23%; CD, 0.22% of PBMC) have slightly lower numbers of circulating DC compared with healthy controls (PDC 0.41%, MDC-1 0.25% of PBMC). In acute flare ups IBD patients experience a significant drop of DC (PDC UC, 0.04%; CD, 0.11%; MDC-1 UC, 0.11%; CD, 0.14% of PBMC) that correlates with disease activity (correlation coefficients: PDC MTWSI, 0.93; HBSI, 0.79; MDC-1 MTWSI, 0.75; HBSI, 0.81). Moreover, both express alpha4beta7 integrin and display an immature phenotype. Freshly isolated PDC and MDC-1 from untreated flaring IBD patients express higher baseline levels of CD86 which increases further in culture and upon stimulation compared with healthy controls. CONCLUSION: IBD patients lack immature blood DC during flare ups which possibly migrate to the gut. An aberrant response to microbial surrogate stimuli suggests a disturbed interaction with commensals.
D C Baumgart; D Metzke; J Schmitz; A Scheffold; A Sturm; B Wiedenmann; A U Dignass
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Gut     Volume:  54     ISSN:  0017-5749     ISO Abbreviation:  Gut     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-01-13     Completed Date:  2005-02-07     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2985108R     Medline TA:  Gut     Country:  England    
Other Details:
Languages:  eng     Pagination:  228-36     Citation Subset:  AIM; IM    
Charité Medical Centre-Virchow Hospital, Medical School of the Humboldt-University, Department of Medicine, Division of Hepatology & Gastroenterology, D-13344 Berlin, Germany.
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MeSH Terms
Acute Disease
Antigens, CD / blood
Antigens, CD86
Cell Differentiation
Cells, Cultured
Colitis, Ulcerative / immunology
Crohn Disease / immunology
Dendritic Cells / pathology*
Inflammatory Bowel Diseases / immunology*
Linear Models
Membrane Glycoproteins / blood
Middle Aged
Myeloid Cells / pathology*
Remission Induction
Severity of Illness Index
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, CD86; 0/CD86 protein, human; 0/Membrane Glycoproteins

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