- Pediatric Gastroenterology
Clinical Assistant Professor, Pediatrics - Gastroenterology
Board Certification: American Board of Pediatrics, Pediatric Gastroenterology (2007)
Fellowship: Stanford University Medical Center (2006) CA
Board Certification: American Board of Pediatrics, Pediatrics (2003)
Residency: Georgetown University Hospital (2003) DC
Internship: Georgetown University Hospital (2001) DC
Medical Education: University of Texas Southwestern Medical School Registrar (2000) TX
Increased Number of Regulatory T Cells in Children With Eosinophilic Esophagitis
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
2010; 51 (3): 283-289
There are limited data on the role of regulatory T cells (Treg) in the disease pathology of eosinophilic esophagitis (EoE). We tested the differences in Treg in subjects with EoE compared with those with gastroesophageal reflux disease (GERD) and healthy controls (HC).Pediatric patients evaluated by endoscopy were recruited for our study. Participants were categorized into 3 groups: EoE, GERD, and HC. RNA purified from esophageal biopsies were used for real-time quantitative polymerase chain reaction assays and tested for forkhead box P3 (FoxP3) mRNA expression. Treg were identified as CD4+CD25hiCD127lo cells in peripheral blood and as CD3+/FoxP3+cells in esophageal tissue.Forty-eight subjects were analyzed by real-time quantitative polymerase chain reaction: EoE (n = 33), GERD (n = 7), and HC (n = 8). FoxP3 expression was higher by up to 1.5-fold in the EoE group compared with the GERD and HC groups (P < 0.05). Protein levels of FoxP3 in blood and tissue were then investigated in 21 subjects: EoE (n = 10), GERD (n = 6), and HC (n = 5). The percentage of Treg and their subsets in peripheral blood were not significant between groups (P > 0.05). The amount of Treg in esophageal tissue was significantly greater in the EoE group (mean 10.7 CD3+/FoxP3+cells/high power field [HPF]) compared with the other groups (GERD, mean 1.7 CD3+/FoxP3+cells/HPF and HC, mean 1.6 CD3+/FoxP3+cells/HPF) (P < 0.05).We show that Treg are increased in esophageal tissue of EoE subjects compared with GERD and HC subjects. The present study illustrates another possible mechanism involved in EoE that implicates impairment of immune homeostasis.
View details for DOI 10.1097/MPG.0b013e3181e0817b
View details for PubMedID 20639775
Increased local and systemic FGF expression in eosinophilic esophagitis
WILEY-BLACKWELL. 2010: 343
View details for Web of Science ID 000329462101384
Eotaxin and FGF enhance signaling through an extracellular signal-related kinase (ERK)-dependent pathway in the pathogenesis of Eosinophilic esophagitis.
Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology
2010; 6 (1): 25-?
Eosinophilic esophagitis (EoE) is characterized by the inflammation of the esophagus and the infiltration of eosinophils into the esophagus, leading to symptoms such as dysphagia and stricture formation. Systemic immune indicators like eotaxin and fibroblast growth factor were evaluated for possible synergistic pathological effects. Moreover, blood cells, local tissue, and plasma from EoE and control subjects were studied to determine if the localized disease was associated with a systemic effect that correlated with presence of EoE disease.Real-time polymerase chain reaction from peripheral blood mononuclear cells (PBMC), immunohistochemistry from local esophageal biopsies, fluid assays on plasma, and fluorescence-activated cell sorting on peripheral blood cells from subjects were used to study the systemic immune indicators in newly diagnosed EoE (n = 35), treated EoE (n = 9), Gastroesophageal reflux disease (GERD) (n = 8), ulcerative colitis (n = 5), Crohn's disease (n = 5), and healthy controls (n = 8).Of the transcripts tested for possible immune indicators, we found extracellular signal-regulated kinase (ERK), Bcl-2, bFGF (basic fibroblast growth factor), and eotaxin levels were highly upregulated in PBMC and associated with disease presence of EoE. Increased FGF detected by immunohistochemistry in esophageal tissues and in PBMC was correlated with low levels of pro-apoptotic factors (Fas, Caspase 8) in PBMC from EoE subjects. Plasma-derived bFGF was shown to be the most elevated and most specific in EoE subjects in comparison to healthy controls and disease control subjects.We describe for the first time a possible mechanism by which increased FGF is associated with inhibiting apoptosis in local esophageal tissues of EoE subjects as compared to controls. Eotaxin and FGF signaling pathways share activation through the ERK pathway; together, they could act to increase eosinophil activation and prolong the half-life of eosinophils in local tissues of the esophagus in EoE subjects.
View details for DOI 10.1186/1710-1492-6-25
View details for PubMedID 20815913
View details for PubMedCentralID PMC2976489
Decreases in circulating CD4(+)CD25(hi)FOXP3(+) cells and increases in intragraft FOXP3(+) cells accompany allograft rejection in pediatric liver allograft recipients
2009; 13 (1): 70-80
We examined CD4(+)CD25(hi)FOXP3(+) cells Treg in children following liver transplantation and determined the relationship between Treg cell levels in the blood and in the graft. Peripheral blood was obtained from pediatric liver transplant patients at sequential time points: pre-transplant, one month, 3-4 months, 6-7 months, and 11-12 months post-transplant. PBMC were isolated, labeled for CD4, CD25 and FOXP3 expression and analyzed by flow cytometry for CD4(+)CD25(hi)FOXP3(+) cells. Sorted CD4(+)CD25(hi) cells were assessed for functional activity. Pretransplant blood levels of CD4(+)CD25(hi)FOXP3(+) Treg cells were not significantly different from post-transplant blood levels of CD4(+)CD25(hi)FOXP3(+) Treg cells. However, the blood levels of CD4(+)CD25(hi)FOXP3(+) Treg cells were significantly decreased during acute rejection compared with levels when graft function was stable. Immunohistochemistry revealed that FOXP3(+) cells were increased in the portal region of livers with histopathologic evidence of acute graft rejection compared with livers without evidence of rejection and were localized primarily within the inflammatory infiltrate. These data indicate that Treg cells are found at the site of allograft rejection and may play a role in regulation of alloreactivity. Moreover, monitoring peripheral CD4(+)CD25(hi)FOXP3(+) Treg cell levels may be useful in improving the post-transplant management of pediatric liver allograft recipients.
View details for DOI 10.1111/j.1399-3046.2008.00917.x
View details for PubMedID 18331536
Trifluoroacetylated IgG4 antibodies in a child with idiosyncratic acute liver failure after first exposure to halothane
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
2008; 47 (2): 199-202
View details for PubMedID 18664874
Cold agglutinin syndrome in pediatric liver transplant recipients
2007; 11 (8): 931-936
Anemia is a common finding in post-liver transplant patients. Causes for the anemia include nutritional deficiencies, red cell aplasia as well as immune-mediated hemolysis. One of the immunologic causes of hemolytic anemia is drug-induced hemolysis. Tacrolimus is a common immunosuppressant used in post-liver transplant patients to prevent graft rejection. There have been reports of tacrolimus-associated hemolytic anemia secondary to hemolytic uremic syndrome as well as autoimmune hemolysis. There are also case-reports of severe hemolytic anemia related to cold agglutinin production in post-liver transplant patients. We described in this paper three cases of severe cold agglutinin hemolytic anemia in three pediatric liver transplant patients. Steroid therapy, plasmapheresis and withdrawal of tacrolimus led to resolution of the severe hemolytic process in each case. Whether the immune-mediated hemolysis is related to tacrolimus is not clear and needs to be characterized further.
View details for DOI 10.1111/j.1399-3046.2007.00795.x
View details for PubMedID 17976131
Peripheral regulatory T cells (CD4+CD25+FOXP3+) as a marker for rejection in pediatric liver transplant patients.
7th American Transplant Congress
WILEY-BLACKWELL. 2007: 278–279
View details for Web of Science ID 000246370200504
Cold agglutinin syndrome in post-liver transplant patients on tacrolimus.
48th Annual Meeting of the American-Society-of-Hematology
AMER SOC HEMATOLOGY. 2006: 288A–289A
View details for Web of Science ID 000242440001227
2005; 44 (7): 641-643
View details for PubMedID 16151574