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

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

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

8. APC Derived IL-8, IL-1 , IL-1 , TNF-  Th-1 Derived IL-2 IFN-γ Cytokines Measured : Th-2 Derived IL-4 IL-6 IL-10 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:

9. P = 0.01 P <0.005 P = 0.004 P = 0.006 P = 0.06 P = 0.04 GFDActivesRefractoryNormal ActivesGFDRefractory IFN-  (pg/ml) IL-4 (pg/ml) RESULTS IFN-  IL-4

10. ACTIVE CD VS. NORMALS IL-4 P <0.004 IL-6 P <0.008 IL-10 P < 0.01 IL-2 P < 0.04 IFN-  P < 0.005 IL-1  P = 0.13 IL-1  P = 0.38 IL-8 P<0.0007 TNF-α P <0.03 APC DerivedTh-2 DerivedTh-1 Derived Active CD n= 25 Controls n= 16

11. GFD vs. Normals IL-4 P <0.0006 IL-6 P <0.015 IL- 10 P = 0.13 IL-2 P = 0.09 IFN-  P < 0.01 IL-1  P = 0.42 IL-1  P = 0.87 IL-8 P <0.003 TNF-α P = 0.09 APC Derived Th-2 Derived Th-1 Derived GFD n= 43 Controls n=16

12. SUMMARY 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

13. 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

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