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Volume 123, Issue 5, Pages (November 2002)

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Presentation on theme: "Volume 123, Issue 5, Pages (November 2002)"— Presentation transcript:

1 Volume 123, Issue 5, Pages 1468-1477 (November 2002)
Dysregulated peripheral and mucosal Th1/Th2 response in Whipple's disease  Thomas Marth, Nicole Kleen, Andreas Stallmach, Sabine Ring, Sheriff Aziz, Carsten Schmidt, Warren Strober, Martin Zeitz, Thomas Schneider  Gastroenterology  Volume 123, Issue 5, Pages (November 2002) DOI: /gast Copyright © 2002 American Gastroenterological Association Terms and Conditions

2 Fig. 1 (A–E) Cytokine production and (F) cell proliferation after in vitro stimulation by PBMCs with phytohemagglutinin from WD patients and healthy donors as determined by enzyme-linked immunosorbent assay and [3H] thymidine incorporation, respectively. The baseline cytokine production and cell proliferation without cell stimulation was generally very low (<3 pg/mL for IL-4; <20 pg/mL for IL-2 and IL-5; <50 pg/mL for IFN-γ; <1000 cpm for thymidine incorporation). Data represent mean ± SEM from 20 WD patients total (as denoted in Patients and Methods section, consisting of group I, n = 5 patients; group II, n = 8 patients [except for IFN-γ and the IFN/IL-4 ratio n = 7]; and group III, n = 7 patients) or mean ± SEM from 14 healthy donors. (A) IL-2 secretion; (B) IFN-γ secretion; (C) IL-4 secretion; (D) IFN-γ /IL-4 ratio; (E) IL-5 secretion; (F) cell proliferation. *P < 0.05, +P < 0.01 vs. controls. ■, All patients; □, controls. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

3 Fig. 2 Monokine production after in vitro stimulation by PBMCs with SAC, SAC + IFN-γ, or LPS + IFN-γ from WD patients and healthy donors as determined by enzyme-linked immunosorbent assay. The number of patients and controls as well as statistics are given in the legend to Figure 1. The baseline cytokine production without stimulation was low (<0.5 pg/mL for IL-12p40; <5 pg/mL for IL-12p70; <1 pg/mL for TNF-α). Data show mean ± SEM from 20 WD patients and mean ± SEM from 14 controls. For IL-12p40 stimulated with SAC + IFN-γ and with LPS + IFN-γ n = 16 (i.e., group I, n = 3; group II, n = 6; and group III, n = 7) and for SAC stimulation n = 15 (same as earlier but group II, n = 5). (A) IL-12p40 secretion–SAC stimulation; (B) IL-12p40 secretion–SAC + IFN-γ stimulation; (C) IL-12p40 secretion–LPS + IFN-γ stimulation; (D) IL-12p70 secretion–SAC + IFN-γ stimulation; (E) IL-12p70 secretion–LPS + IFN-γ stimulation; (F) TNF-α secretion–LPS + IFN-γ stimulation. *P < 0.05, and +P < 0.01 vs. controls. ■, All patients; □, controls. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

4 Fig. 3 Subgroup analysis. Cytokine and monokine production as well as cell proliferation after in vitro stimulation by PBMCs from different WD patient groups (●, group I, n = 5 patients; ●, group II, n = 8 patients; ▩, group III, n = 7 patients; in some tests only up to 15 patients were available, see legends to Figures 1 and 2) determined by techniques as detailed in the legends to Figures 1 and 2. (A) IL-2 secretion; (B) IFN-γ secretion; (C) IL-4 secretion; (D) IFN-γ/IL-4 ratio; (E) IL-5 secretion; (F) cell proliferation; (G) IL-12p40 secretion–SAC stimulation; (H) IL-12p40 secretion–SAC + IFN-γ stimulation; (I) IL-12p40 secretion–LPS + IFN-γ stimulation; (J) IL-12p70 secretion–SAC + IFN-γ stimulation; (K) IL-12p70 secretion–LPS + IFN-γ stimulation; (L) TNF-α secretion–LPS + IFN-γ stimulation. Data show mean ± SEM from the indicated WD patient groups. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

5 Fig. 4 Reduced intestinal CD4+ T-cell numbers in WD. After the isolation of LPMCs from biopsy specimens of WD patients, from normal controls and from patients with chronic H. pylori infection, CD4 T-cell numbers were determined by flow cytometry as described in the Patients and Methods section. Shown is a box plot analysis with the median (thick line), the 75% and 25% percentile (upper and lower box limits), and the standard deviation; the group size was 6 individuals each (for WD patients 2 patients each from groups I to III). The difference of the WD group was statistically significant (P < 0.05) compared with the other groups. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

6 Fig. 5 Impaired mucosal IFN-γ secretion. The production of IFN-γ from WD LPMCs and control LPMCs stimulated with anti-CD2/CD28 was determined as described in the Patients and Methods section. The difference from WD to controls was significantly different as determined by the 2-sided Wilcoxon rank test (P < 0.05). □, Individual value; ▩, group median. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions


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