T-cell activation Rho GTPase-activating protein expression varies with inflammation location and severity in Crohn's disease

Tara M. Connelly, Arthur S. Berg, Leonard R. Harris, John P. Hegarty, Francesca M. Ruggiero, Susan M. Deiling, David L. Brinton, Walter A. Koltun

Research output: Contribution to journalArticle

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Abstract

Background The T-cell activation Rho GTPase-activating protein (TAGAP) gene has a regulatory role in T cell activation. We have previously suggested a correlation between the TAGAP-associated single nucleotide polymorphism rs212388 and protection from anal sepsis in Crohn's disease (CD) patients. The present study sought to evaluate TAGAP's expression in colonic tissue of CD patients with varying disease severity and location. Materials and methods Five transverse, 17 left, and five sigmoid colectomy specimens from 27 CD patients with varying disease severity (16 male, mean age at diagnosis 26.4 ± 2.2 y) were evaluated for TAGAP messenger RNA expression. Fisher exact, Mann-Whitney, and Welch two-sample t-tests were used for statistical evaluation. Immunohistochemistry confirmed results. Results Patients with tissue demonstrating lower TAGAP messenger RNA expression (less than the overall mean) were younger at diagnosis (mean age 21.1 ± 6.3 versus 32.5 ± 13 y, P = 0.009). Increased TAGAP expression was seen in moderate or severely diseased tissue versus tissue with no or mild disease (RQ = 1.3 ± 0.34 versus 0.53 ± 0.09, P = 0.050). This was the most dramatic in the sigmoid colon (P = 0.041). TAGAP expression was increased in more distal tissue with a significant difference seen when comparing transverse versus sigmoid colon with moderate or severe disease (0.51 ± 0.14 versus 1.9 ± 0.37, P = 0.049). Conclusions Colonic expression of TAGAP in CD patients varied according to disease severity and location, being the most elevated in patients with severe disease in the sigmoid colon. Whether changes in TAGAP expression are a result of disease response or inherent to the disease pathophysiology itself remains to be determined. This gene warrants further investigation for its role in CD.

Original languageEnglish (US)
Pages (from-to)457-464
Number of pages8
JournalJournal of Surgical Research
Volume190
Issue number2
DOIs
StatePublished - Aug 2014

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Crohn Disease
Inflammation
T-Lymphocytes
Sigmoid Colon
Sigmoid Diseases
rho GTPase-activating protein
Messenger RNA
Colectomy
Genes
Single Nucleotide Polymorphism
Sepsis
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Connelly, Tara M. ; Berg, Arthur S. ; Harris, Leonard R. ; Hegarty, John P. ; Ruggiero, Francesca M. ; Deiling, Susan M. ; Brinton, David L. ; Koltun, Walter A. / T-cell activation Rho GTPase-activating protein expression varies with inflammation location and severity in Crohn's disease. In: Journal of Surgical Research. 2014 ; Vol. 190, No. 2. pp. 457-464.
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title = "T-cell activation Rho GTPase-activating protein expression varies with inflammation location and severity in Crohn's disease",
abstract = "Background The T-cell activation Rho GTPase-activating protein (TAGAP) gene has a regulatory role in T cell activation. We have previously suggested a correlation between the TAGAP-associated single nucleotide polymorphism rs212388 and protection from anal sepsis in Crohn's disease (CD) patients. The present study sought to evaluate TAGAP's expression in colonic tissue of CD patients with varying disease severity and location. Materials and methods Five transverse, 17 left, and five sigmoid colectomy specimens from 27 CD patients with varying disease severity (16 male, mean age at diagnosis 26.4 ± 2.2 y) were evaluated for TAGAP messenger RNA expression. Fisher exact, Mann-Whitney, and Welch two-sample t-tests were used for statistical evaluation. Immunohistochemistry confirmed results. Results Patients with tissue demonstrating lower TAGAP messenger RNA expression (less than the overall mean) were younger at diagnosis (mean age 21.1 ± 6.3 versus 32.5 ± 13 y, P = 0.009). Increased TAGAP expression was seen in moderate or severely diseased tissue versus tissue with no or mild disease (RQ = 1.3 ± 0.34 versus 0.53 ± 0.09, P = 0.050). This was the most dramatic in the sigmoid colon (P = 0.041). TAGAP expression was increased in more distal tissue with a significant difference seen when comparing transverse versus sigmoid colon with moderate or severe disease (0.51 ± 0.14 versus 1.9 ± 0.37, P = 0.049). Conclusions Colonic expression of TAGAP in CD patients varied according to disease severity and location, being the most elevated in patients with severe disease in the sigmoid colon. Whether changes in TAGAP expression are a result of disease response or inherent to the disease pathophysiology itself remains to be determined. This gene warrants further investigation for its role in CD.",
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T-cell activation Rho GTPase-activating protein expression varies with inflammation location and severity in Crohn's disease. / Connelly, Tara M.; Berg, Arthur S.; Harris, Leonard R.; Hegarty, John P.; Ruggiero, Francesca M.; Deiling, Susan M.; Brinton, David L.; Koltun, Walter A.

In: Journal of Surgical Research, Vol. 190, No. 2, 08.2014, p. 457-464.

Research output: Contribution to journalArticle

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T1 - T-cell activation Rho GTPase-activating protein expression varies with inflammation location and severity in Crohn's disease

AU - Connelly, Tara M.

AU - Berg, Arthur S.

AU - Harris, Leonard R.

AU - Hegarty, John P.

AU - Ruggiero, Francesca M.

AU - Deiling, Susan M.

AU - Brinton, David L.

AU - Koltun, Walter A.

PY - 2014/8

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N2 - Background The T-cell activation Rho GTPase-activating protein (TAGAP) gene has a regulatory role in T cell activation. We have previously suggested a correlation between the TAGAP-associated single nucleotide polymorphism rs212388 and protection from anal sepsis in Crohn's disease (CD) patients. The present study sought to evaluate TAGAP's expression in colonic tissue of CD patients with varying disease severity and location. Materials and methods Five transverse, 17 left, and five sigmoid colectomy specimens from 27 CD patients with varying disease severity (16 male, mean age at diagnosis 26.4 ± 2.2 y) were evaluated for TAGAP messenger RNA expression. Fisher exact, Mann-Whitney, and Welch two-sample t-tests were used for statistical evaluation. Immunohistochemistry confirmed results. Results Patients with tissue demonstrating lower TAGAP messenger RNA expression (less than the overall mean) were younger at diagnosis (mean age 21.1 ± 6.3 versus 32.5 ± 13 y, P = 0.009). Increased TAGAP expression was seen in moderate or severely diseased tissue versus tissue with no or mild disease (RQ = 1.3 ± 0.34 versus 0.53 ± 0.09, P = 0.050). This was the most dramatic in the sigmoid colon (P = 0.041). TAGAP expression was increased in more distal tissue with a significant difference seen when comparing transverse versus sigmoid colon with moderate or severe disease (0.51 ± 0.14 versus 1.9 ± 0.37, P = 0.049). Conclusions Colonic expression of TAGAP in CD patients varied according to disease severity and location, being the most elevated in patients with severe disease in the sigmoid colon. Whether changes in TAGAP expression are a result of disease response or inherent to the disease pathophysiology itself remains to be determined. This gene warrants further investigation for its role in CD.

AB - Background The T-cell activation Rho GTPase-activating protein (TAGAP) gene has a regulatory role in T cell activation. We have previously suggested a correlation between the TAGAP-associated single nucleotide polymorphism rs212388 and protection from anal sepsis in Crohn's disease (CD) patients. The present study sought to evaluate TAGAP's expression in colonic tissue of CD patients with varying disease severity and location. Materials and methods Five transverse, 17 left, and five sigmoid colectomy specimens from 27 CD patients with varying disease severity (16 male, mean age at diagnosis 26.4 ± 2.2 y) were evaluated for TAGAP messenger RNA expression. Fisher exact, Mann-Whitney, and Welch two-sample t-tests were used for statistical evaluation. Immunohistochemistry confirmed results. Results Patients with tissue demonstrating lower TAGAP messenger RNA expression (less than the overall mean) were younger at diagnosis (mean age 21.1 ± 6.3 versus 32.5 ± 13 y, P = 0.009). Increased TAGAP expression was seen in moderate or severely diseased tissue versus tissue with no or mild disease (RQ = 1.3 ± 0.34 versus 0.53 ± 0.09, P = 0.050). This was the most dramatic in the sigmoid colon (P = 0.041). TAGAP expression was increased in more distal tissue with a significant difference seen when comparing transverse versus sigmoid colon with moderate or severe disease (0.51 ± 0.14 versus 1.9 ± 0.37, P = 0.049). Conclusions Colonic expression of TAGAP in CD patients varied according to disease severity and location, being the most elevated in patients with severe disease in the sigmoid colon. Whether changes in TAGAP expression are a result of disease response or inherent to the disease pathophysiology itself remains to be determined. This gene warrants further investigation for its role in CD.

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