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Expression of TIM-3, Human β-defensin-2, and FOXP3 and Correlation with Disease Activity in Pediatric Crohn's Disease with Infliximab Therapy.

Kim MJ, Lee WY, Choe YH - Gut Liver (2015)

Bottom Line: A significant difference in HBD-2 mRNA expression was found in colonic mucosa between CD patients before infliximab therapy and the healthy controls (p=0.013).Our study suggests that both the adaptive and innate immune systems are closely linked to each other in CD pathogenesis.And the results of our study indicate that it could be a useful therapeutic tool, where restoration of TIM-3, HBD-2 and the function of Tregs may repair the dysfunctional immunoregulation in CD.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea.

ABSTRACT

Background/aims: This study investigated the expression of T cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3), human β-defensin (HBD)-2, forkhead box protein 3 (FOXP3), and the frequency of CD4(+) CD25(+) FOXP3(+) regulatory T cells (Tregs) in children with Crohn's disease (CD) during infliximab therapy.

Methods: We enrolled 20 CD patients who received infliximab treatment for 1 year. Peripheral blood and colonic mucosal specimens were collected from all CD patients and from healthy control individuals.

Results: A significant difference in TIM-3 mRNA expression was evident in peripheral blood mononuclear cells and colonic mucosa between CD patients before infliximab therapy and the healthy controls (p<0.001 and p=0.005, respectively). A significant difference in HBD-2 mRNA expression was found in colonic mucosa between CD patients before infliximab therapy and the healthy controls (p=0.013). In the active phase of CD, at baseline, the median percentage of T cells that were CD25(+) FOXP3(+) was 1.5% (range, 0.32% to 3.49%), which increased after inflixmab treatment for 1 year to 2.2% (range, 0.54% to 5.02%) (p=0.008).

Conclusions: Our study suggests that both the adaptive and innate immune systems are closely linked to each other in CD pathogenesis. And the results of our study indicate that it could be a useful therapeutic tool, where restoration of TIM-3, HBD-2 and the function of Tregs may repair the dysfunctional immunoregulation in CD.

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Expression of human β-defensin (HBD)-2 mRNA in the colonic mucosa and its correlation with disease activity. (A) The expression of HBD-2 mRNA in the colonic mucosa of the Crohn’s disease (CD) patients and healthy controls was determined by real-time reverse transcription-polymerase chain reaction. The HBD-2 mRNA expression in the colonic mucosa of CD patients before infliximab therapy (IFX Tx) was significantly higher than that in the healthy controls (p=0.013). After IFX Tx, HBD-2 mRNA expression was decreased compared with that before therapy (p=0.017). Box plots define the values for the median, range, and 25th and 75th percentiles. The range is represented by the upper and lower limits of the vertical lines. (B) A negative correlation was found between the T cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) mRNA expression in peripheral blood mononuclear cells and the HBD-2 mRNA expression in the colonic mucosa in the CD patients (r2=0.344, p=0.007). (C) Correlation of HBD-2 mRNA expression in the colonic mucosa with the clinical disease activity index during IFX Tx (r2=0.074, p=0.091).
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f5-gnl-09-370: Expression of human β-defensin (HBD)-2 mRNA in the colonic mucosa and its correlation with disease activity. (A) The expression of HBD-2 mRNA in the colonic mucosa of the Crohn’s disease (CD) patients and healthy controls was determined by real-time reverse transcription-polymerase chain reaction. The HBD-2 mRNA expression in the colonic mucosa of CD patients before infliximab therapy (IFX Tx) was significantly higher than that in the healthy controls (p=0.013). After IFX Tx, HBD-2 mRNA expression was decreased compared with that before therapy (p=0.017). Box plots define the values for the median, range, and 25th and 75th percentiles. The range is represented by the upper and lower limits of the vertical lines. (B) A negative correlation was found between the T cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) mRNA expression in peripheral blood mononuclear cells and the HBD-2 mRNA expression in the colonic mucosa in the CD patients (r2=0.344, p=0.007). (C) Correlation of HBD-2 mRNA expression in the colonic mucosa with the clinical disease activity index during IFX Tx (r2=0.074, p=0.091).

Mentions: HBD-2 mRNA expression in the colonic mucosa was examined using quantitative real-time RT-PCR. A significant difference in HBD-2 mRNA expression was found between colonic mucosa from CD patients before infliximab therapy and that from healthy controls (p=0.013) (Fig. 5A). After infliximab therapy, HBD-2 mRNA expression in CD patients was decreased compared to that before therapy (p=0.017) (Fig. 5A). A negative correlation was found between TIM-3 mRNA expression in PBMC and HBD-2 mRNA expression in colonic mucosa from CD patients (r2=0.344, p=0.007) (Fig. 5B). However, a correlation was not found between HBD-2 mRNA expression in colonic mucosa from CD patients and PCDAI during infliximab therapy (r2=0.074, p=0.091) (Fig. 5C).


Expression of TIM-3, Human β-defensin-2, and FOXP3 and Correlation with Disease Activity in Pediatric Crohn's Disease with Infliximab Therapy.

Kim MJ, Lee WY, Choe YH - Gut Liver (2015)

Expression of human β-defensin (HBD)-2 mRNA in the colonic mucosa and its correlation with disease activity. (A) The expression of HBD-2 mRNA in the colonic mucosa of the Crohn’s disease (CD) patients and healthy controls was determined by real-time reverse transcription-polymerase chain reaction. The HBD-2 mRNA expression in the colonic mucosa of CD patients before infliximab therapy (IFX Tx) was significantly higher than that in the healthy controls (p=0.013). After IFX Tx, HBD-2 mRNA expression was decreased compared with that before therapy (p=0.017). Box plots define the values for the median, range, and 25th and 75th percentiles. The range is represented by the upper and lower limits of the vertical lines. (B) A negative correlation was found between the T cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) mRNA expression in peripheral blood mononuclear cells and the HBD-2 mRNA expression in the colonic mucosa in the CD patients (r2=0.344, p=0.007). (C) Correlation of HBD-2 mRNA expression in the colonic mucosa with the clinical disease activity index during IFX Tx (r2=0.074, p=0.091).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4413971&req=5

f5-gnl-09-370: Expression of human β-defensin (HBD)-2 mRNA in the colonic mucosa and its correlation with disease activity. (A) The expression of HBD-2 mRNA in the colonic mucosa of the Crohn’s disease (CD) patients and healthy controls was determined by real-time reverse transcription-polymerase chain reaction. The HBD-2 mRNA expression in the colonic mucosa of CD patients before infliximab therapy (IFX Tx) was significantly higher than that in the healthy controls (p=0.013). After IFX Tx, HBD-2 mRNA expression was decreased compared with that before therapy (p=0.017). Box plots define the values for the median, range, and 25th and 75th percentiles. The range is represented by the upper and lower limits of the vertical lines. (B) A negative correlation was found between the T cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) mRNA expression in peripheral blood mononuclear cells and the HBD-2 mRNA expression in the colonic mucosa in the CD patients (r2=0.344, p=0.007). (C) Correlation of HBD-2 mRNA expression in the colonic mucosa with the clinical disease activity index during IFX Tx (r2=0.074, p=0.091).
Mentions: HBD-2 mRNA expression in the colonic mucosa was examined using quantitative real-time RT-PCR. A significant difference in HBD-2 mRNA expression was found between colonic mucosa from CD patients before infliximab therapy and that from healthy controls (p=0.013) (Fig. 5A). After infliximab therapy, HBD-2 mRNA expression in CD patients was decreased compared to that before therapy (p=0.017) (Fig. 5A). A negative correlation was found between TIM-3 mRNA expression in PBMC and HBD-2 mRNA expression in colonic mucosa from CD patients (r2=0.344, p=0.007) (Fig. 5B). However, a correlation was not found between HBD-2 mRNA expression in colonic mucosa from CD patients and PCDAI during infliximab therapy (r2=0.074, p=0.091) (Fig. 5C).

Bottom Line: A significant difference in HBD-2 mRNA expression was found in colonic mucosa between CD patients before infliximab therapy and the healthy controls (p=0.013).Our study suggests that both the adaptive and innate immune systems are closely linked to each other in CD pathogenesis.And the results of our study indicate that it could be a useful therapeutic tool, where restoration of TIM-3, HBD-2 and the function of Tregs may repair the dysfunctional immunoregulation in CD.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea.

ABSTRACT

Background/aims: This study investigated the expression of T cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3), human β-defensin (HBD)-2, forkhead box protein 3 (FOXP3), and the frequency of CD4(+) CD25(+) FOXP3(+) regulatory T cells (Tregs) in children with Crohn's disease (CD) during infliximab therapy.

Methods: We enrolled 20 CD patients who received infliximab treatment for 1 year. Peripheral blood and colonic mucosal specimens were collected from all CD patients and from healthy control individuals.

Results: A significant difference in TIM-3 mRNA expression was evident in peripheral blood mononuclear cells and colonic mucosa between CD patients before infliximab therapy and the healthy controls (p<0.001 and p=0.005, respectively). A significant difference in HBD-2 mRNA expression was found in colonic mucosa between CD patients before infliximab therapy and the healthy controls (p=0.013). In the active phase of CD, at baseline, the median percentage of T cells that were CD25(+) FOXP3(+) was 1.5% (range, 0.32% to 3.49%), which increased after inflixmab treatment for 1 year to 2.2% (range, 0.54% to 5.02%) (p=0.008).

Conclusions: Our study suggests that both the adaptive and innate immune systems are closely linked to each other in CD pathogenesis. And the results of our study indicate that it could be a useful therapeutic tool, where restoration of TIM-3, HBD-2 and the function of Tregs may repair the dysfunctional immunoregulation in CD.

Show MeSH
Related in: MedlinePlus