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Humoral Rejection in Allografts And Gene Expression

Humoral Rejection in Allografts And Gene Expression. Anatasia Gangadin Dr. Mario C Deng Columbia University College of Physicians and Surgeons. Key Ideas. Allograft Endomyocardial Biopsy Rejection CARGO Functional Genomics Patient Care. Patient Care. Endomyocardial biopsy.

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Humoral Rejection in Allografts And Gene Expression

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  1. Humoral Rejection in Allografts And Gene Expression Anatasia Gangadin Dr. Mario C Deng Columbia University College of Physicians and Surgeons

  2. Key Ideas • Allograft • Endomyocardial Biopsy • Rejection • CARGO • Functional Genomics • Patient Care

  3. Patient Care

  4. Endomyocardial biopsy • Currently Only way to test for rejection • Risk Factors associated

  5. Rejection Mild Severe

  6. CARGO Study • To Reduce the Number of Biopsies by taking samples of blood as opposed to heart Tissue • Being able to predict rejection after a transplant • Establishing a pattern of Genes which could ultimately predict Rejection

  7. Basic Forms Of Rejection

  8. Humoral Rejection • Accounts for 20-30% of rejections in allografts. • Common Risk Factors • Causes hemodynamic dysfunction (shock, hypertension, decreased cardiac output, and rise in pulmonary artery pressure).

  9. How Humoral Rejection Works

  10. HLA Antigen Displayed CD4 T Cell receptor CD8

  11. Gene Expression When Lymphocytes release specific cytokines and plasma cells, They are doing so because of the patient’s gene Expression, which is why some patients experience rejection or no Rejection.

  12. Experiment Aim: To compare genomic data in 121 patients and to discover a set of genes which can be used to predict Present/Future Humoral Rejection. Inclusion: • Patients with Heart Transplants within past 6 months • Patients >18 Exclusion: • Patients with Oversensitive Immune Systems • Patients > 1 transplant

  13. Methods • Gene Microarray Analysis • CD4 Staining • Gene Microarray and Statistical Analysis

  14. Gene Microarray Analysis

  15. C4D Staining

  16. Genes

  17. Future Research • To Perform Microarrays in order to pinpoint specific genes from patient blood • To sample patient blood for CD4 which may detect rejection, instead of heart tissue

  18. References • Marboe C, Deng MC, Billingham M. Nodular Endocardial Infiltrates (Quilty Lesions) Cause A Significant Variability in Diagnosis of ISHLT Grade 2 and 3A Rejection in Cardiac Allograft Recipients. Journal of Heart and Lung Transplantation July 2005; 24:s219-s226. • Evans R, Williams G, Deng MC. The Economic Implications of Noninvasive Molecular Testing for Cardiac Allograft Rejection. American Journal of Transplantation 2005; 5:1553-1558 • Deng MC, Eisen HJ, Mehra MR. Noninvasive Discrimination of Rejection in Cardiac Allograft Recipients Using gene Expression Profiling. American Journal of Transplantation 2006; 6:150-160 • Deng MC. Cardiac Transplantation. Heart 2002; 87:177-184 • Michaels PJ, Fishbein MC, Colvin RB. Humoral rejection of Human organ Transplants. Springer Seminars in Immunopathology 2003 119-140.

  19. Acknowledgements • Dr. Mario Deng • Martin Cadeiras • Manuel Prinz von Bayern • Sarfaraz Memon • Dr. Sat Bhattacharya • Columbia College of Physicians and Surgeons • Memorial Sloane Kettering Cancer Center • Harlem Children Society

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