Reduction of Dendritic Cells by Granulocyte and Monocyte Adsorption Apheresis in Patients with Ulcerative Colitis
Department of Internal Medicine, Division of Gastroenterology, University of Rostock, Ernst-Heydemann-Strasse 6, Rostock, Germany. Digestive Diseases and Sciences
(Impact Factor: 2.61).
03/2008; 53(9):2507-15. DOI: 10.1007/s10620-007-0168-8
The influence of the granulocyte/monocyte apheresis (GMCAP) on cell populations participating in mechanisms of tolerance, e.g. dendritic cells (DCs), is still not very clear. In a first step, we aimed to investigate changes in the DC population of patients suffering from ulcerative colitis (UC) (n = 13) compared to healthy subjects (n = 9). In a second step, we studied the changes in peripheral DCs in a small group of patients with active UC before and after Adacolumn apheresis (n = 7). For this purpose, plasmacytoid and myeloid DCs and their maturation markers CD40, CD80, and CD86 were measured using four-color flow cytometry in the peripheral blood. After apheresis, and in acute flare-ups, we identified a significantly lower number of lymphocytes, plasmacytoid, and myeloid DCs. In conclusion, the additional removal of peripheral DCs by GMCAP, which otherwise would contribute to the inflammatory process in the gut, may lead to a higher tolerogeneic status towards luminal antigens.
Available from: Renata D'Incà
- "In fact, interleukin-6 mRNA and interleukin-8 mRNA return to normal levels following GMA.28 Moreover, the clinical efficacy of GMA in IBD appears to be associated with an increase in circulating T regulatory lymphocytes, with a higher expression of FoxP3 in CD4+ T cells29 and with a reduction of both myeloid and plasmocytoid dendritic populations.30 Generally speaking, several elements indicate that, in addition to removal of activated cells, a reactive immunomodulatory effect is one of the mechanisms of action of GMA. "
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ABSTRACT: Granulocyte-monocyte apheresis is a relatively new therapy that has been proposed, sometimes with controversial results, for the treatment of inflammatory bowel disease, particularly ulcerative colitis. The aim of the present study was to perform a thorough review of the literature on the application of this type of treatment in ulcerative colitis and discuss the results, in order to provide an opinion on its use which is shared by the involved experts. The review of the literature was performed by searching PubMed with appropriate key words. The results obtained suggest that the major role for this treatment at this moment is for those patients with steroid dependency or with major contraindications to use of steroids. However, promising, albeit very preliminary, results have also been observed in steroid-naïve subjects, and this is of particular interest in consideration of the safety profile of this therapeutic method. As such, the Adacolumn may prove useful in specific subgroups of patients. Future phenotypic, genotypic, and molecular characterization of patients with inflammatory bowel disease might prove useful in defining better those subjects who might benefit most from this treatment modality.
Clinical and Experimental Gastroenterology 01/2013; 6(1):1-7. DOI:10.2147/CEG.S33275
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ABSTRACT: Two main functionally distinct monocytes phenotypes are known: the CD14(hi)CD16(-) "classical" and the CD14(+)CD16(+) "proinflammatory" phenotypes. The latter phenotype is elevated in patients with ulcerative colitis (UC) and is suspected to have a major role in the immunopathogenesis of UC.
To selectively deplete circulating proinflammatory CD14(+)CD16(+) monocyte phenotype.
Seven corticosteroid-naïve patients with UC (clinical activity index = 8.7 +/- 1.3) and seven healthy subjects were included. In patients with UC, granulocyte/monocyte adsorption (GMA) was done with an Adacolumn that selectively adsorbs leucocytes of the myeloid lineage. Blood from all subjects at baseline and from the patients immediately after the first GMA session was processed. Isolated monocytes were subjected to fluorescence-activated cell sorter analyses.
The seven UC patients achieved remission (CAI <or=4) after 5-10 GMA sessions. GMA induced a strong fall in the ratio (%) of CD14(+)CD16(+) to CD14(hi)CD16(-) monocytes, from 10.0 +/- 1.4 to 3.0 +/- 0.9. Further, expressions of alpha4 integrin (374.8 +/- 26.1 mean fluorescence intensity, MFI) and CX(3)CR1 (49.5 +/- 4.6 MFI) were significantly high on CD14(+)CD16(+)monocytes as compared with on CD14(hi)CD16(-) monocytes (169.2 +/- 17.2 and 33.2 +/- 3.6 MFI, respectively). Additionally, GMA significantly increased the ratio of the CD14(hi)CD16(-)CCR2(low) "immature" monocytes from 3.74 +/- 0.62 to 8.11 +/- 0.56 MFI.
We found high expressions of alpha4 integrin and CX(3)CR1 on monocytes in patients with active UC, known to promote the extravasation of CD14(+)CD16(+) monocytes into the mucosa. GMA effectively depletes CD14(+)CD16(+) monocytes and concomitantly increases CD14(hi)CD16(-)CCR2(low) "immature" monocytes; thus GMA was associated with the emergence of less inflammatory monocyte phenotype in circulation.
Digestive Diseases and Sciences 11/2009; 55(7):1886-95. DOI:10.1007/s10620-009-0974-2 · 2.61 Impact Factor
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ABSTRACT: In human blood, two main subsets of antigen-presenting-cells (APCs) have been described: plasmocytoid dendritic cells (pDC) and myeloid dendritic cells (mDC) which are further subdivided in CD11c-mDC and CD16-mDC DC. In ulcerative colitis patients (UC) peripheral blood APCs express significant levels of the activation and lack immature-tolerogeneic APCs. Adacolumn selective granulocytapheresis (GCAP) has been associated with clinical efficacy in patients with UC. In the present study we sought the effect of sequential GCAP procedures in peripheral blood APCs in patients with UC and the effect on soluble cytokines.
We used multiparametric flow cytometry to quantify peripheral blood APCs and serum cytokines in 210 samples obtained from seven patients with steroid-dependent or steroid resistant UC undergoing GCAP treatment. Samples were drawn before, after 30 and 60 min of each session.
Each GCAP session resulted in a dramatic tenfold reduction of peripheral blood CD16-mDC (P < 0.01), pDC decreased twofold (P = 0.05) but CD11c-mDC remained unchanged. This depletion was reached after 30 min and maintained at 60 min. The depletion of CD16-mDC and monocytes was associated with a reduction of serum tumor necrosis factor levels and a raise in interleukin-10 levels, although no statistical difference was reached.
The effect of GCAP in peripheral blood APC consisted mainly on a significant depletion of tumor necrosis factor-α secreting CD16-mDC. This finding could suggest a potential mechanism of GCAP beneficial effect that must be confirmed in larger series.
Journal of Gastroenterology and Hepatology 12/2010; 25(12):1869-75. DOI:10.1111/j.1440-1746.2010.06377.x · 3.50 Impact Factor
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