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SERUM CYTOKINE PATTERNS IN CELIAC DISEASE

SERUM CYTOKINE PATTERNS IN CELIAC DISEASE. Shabab Naqvi & Ibrahim Ibrahim Mentor: Dr. Sanil Manavalan Columbia University, College of Physicians and Surgeons. Celiac disease a digestive disease that damages the small intestine and interferes with absorption of nutrients from food

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SERUM CYTOKINE PATTERNS IN CELIAC DISEASE

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  1. SERUM CYTOKINE PATTERNS IN CELIAC DISEASE Shabab Naqvi & Ibrahim Ibrahim Mentor: Dr. Sanil Manavalan Columbia University, College of Physicians and Surgeons

  2. Celiac disease • a digestive disease that damages the small intestine and interferes with absorption of nutrients from food • it is a genetic disorder • some of the symptoms of celiac disease are diarrhea, weight loss, malnutrition, etc • when people with celiac disease eat foods containing gluten, their immune system responds by damaging the small intestine • Diagnosis is by intestinal biopsy histological grading and presence of serum auto- antibodies.

  3. Key Terms • Cytokines – soluble peptides or glycoproteins that regulate immune, inflammatory responses and other biologic processes. • Interleukin (IL) – cytokines that only affect leukocytes. • Lymphocyte – A type of leukocyte (white blood cell) of the immune system. • T-Regulatory Cell – slows down and stops immune response • T-Helper Cell (Th cell) – has antigen-receptors, releases cytokines • Natural Killer Cell – kills macrophage and bad stuff • Cytotoxic T-Cell – kills cells that produce foreign antigens such as cells infected by viruses • B-Cell – creates antibodies. • Antigen – invading microbe • Antibody– protein that fights bacteria and viruses.

  4. The Gut Lumen

  5. Inflammation & Damaged enterocytes Helper T cell Plasma cells Antibodies anti-gliadin anti-endomysial And tissue trasgliutaminase ab T cell receptor HLA-DQ2/DQ8 molecule Lymphocytes (T cells , Natural Killer cells and B cells) Cytokines (Interferon-g, TNF-a, IL-15 etc) Antigen Presenting Cell GUT LUMEN GUT LUMEN Gliadin Enterocytes LAMINA PROPRIA AND INTRA EPITHILIAL SPACE

  6. AIMS Define the serum cytokine profile in patients with Celiac Disease: A) Active Disease B) Gluten Free Diet (GFD) C) Refractory disease (RD) D) Normals/Controls

  7. METHODOLOGY Serum Samples from: A) Active Disease (25) B) Gluten Free Diet (GFD) (43) C) Refractory disease (6) D) Controls (16) Measured using a Cytokine Bio-chip Array (RANDOX laboratories Ltd) Mann-Whitney Rank test and Student T-test to determine differences in the means of individual groups of patients: Cytokines Measured: Th-1 Derived IL-2 IFN-γ Th-2 Derived IL-4 IL-6 IL-10 APC Derived IL-8, IL-1a, IL-1b, TNF-a

  8. Normal Actives GFD Refractory Normal Actives GFD Refractory IFN-g IL-4 RESULTS P = 0.01 P = 0.006 P = 0.06 IL-4 (pg/ml) P <0.005 P = 0.04 IFN-g (pg/ml) P = 0.004

  9. Th-1 Derived Th-2 Derived APC Derived ACTIVE CD VS. NORMALS Active CD n= 25 Controls n= 16

  10. GFD vs. Normals APC Derived Th-2 Derived Th-1 Derived GFD n= 43 Controls n=16

  11. Patients with Celiac Disease (AD, GFD or RD) have significantly higher levels of pro-inflammatory, TH1( (IFN-γ) and TH2 (IL-4, IL-6, IL-8) cytokines when compared to normal controls. Patients on therapy (gluten-free-diet) had fewer pro-inflammatory cytokines with elevated levels than Active disease patients SUMMARY

  12. CONCLUSIONS A better understanding of cytokine abnormalities may provide insight into: -Systemic symptoms -Disease pathogenesis -Better monitoring of disease activity -New therapeutic and prognostic modalities

  13. THANK YOU To: Dr. Sanil Manavalan Dr. Jamal Naiyer Dr. Sat Bhattacharya Harlem Children Society

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