Journal of Vaccines & Vaccination

Underlying novel molecular genetic defects and immunopathological mechanisms in Pakistani patients with BCG complications

7^th Middle East - Global Summit and Expo on Vaccines & Vaccination

September 28-29, 2015 Dubai, UAE

Taj Ali Khan

Kohat Univerity of Science & Technology, Pakistan

Scientific Tracks Abstracts: J Vaccines Vaccin

Abstract:

Background: The attenuated bacille Calmette-Guérin (BCG) vaccine is a widely practiced vaccine in many countries including Pakistan for prophylaxis against tuberculosis. BCG-itis and BCG-osis can be associated with BCG vaccine in patients with an underlying immunodeficiency. This study was performed to determine the underlying novel defects in patients with BCG complications. Methods: Clinical data of patients were obtained from the medical records. Molecular and immunological evaluation was performed in children who developed BCG-itis (both auxiliary and cervical adenitis) after vaccinatio. Peripheral blood mononuclear cells (PBMCs) from the patients and healthy controls were evaluated for the ability to produce IFN-γ and IL-12, to phosphorylate STAT1 and STAT4, and to express the IFN-γ and IL-12 receptors in order to screen or confirm possible defects in the IL-12/IFN-γ axis. In addition, defects in toll-like receptor (TLR) signaling were analyzed by measuring the shedding of CD62L on neutrophils, TLR expression, and IkBα degradation in monocytes. Defects of NADPH oxidase components were evaluated by dihydrorhodamine (DHR) assay and NADPH proteins expression. Genetic analysis was performed by Sanger sequencing. Moncoytes-derived macrophages (MDMs) were evaluated for their capacity to phagocytose and control intracellular Mycobacterium tuberculosis growth. Results: Functional and molecular abnormalities were identified in IL-12/IFN-g axis, TLR signaling and NADPH oxidase complex. Conclusion: Pakistani patients have heterogeneous mutations associated with susceptibility to BCG complication. In addition, the inability of MDMs to control the intracellular growth of M. tuberculosis indicates this contributes to patients´ susceptibility to mycobacterial infections. Live vaccines such as BCG should be postponed for a few months�?? in suspected cases of primary immunodeficiency disease, until appropriate screening tests exclude this diagnosis.

Biography :

Taj Ali Khan has completed his PhD from University of Sao Paulo, Brazil and applied for the Postdoctoral studies in the same University. He is the Faculty Member in the Department of Microbiology, KUST, KPK, Pakistan. He has published more than 4 papers in reputed journals and many are in preparation.

Email: microbiologist63@yahoo.com