DETECTION AND CHARACTERIZATION OF ANTI-IFN-Γ AUTOANTIBODY IN PATIENTS WITH ADULT-ONSET IMMUNODEFICIENCY SYNDROME

Dyah Ika Krisnawati

Abstract


Interferon (IFN)-γ, a type II IFN produced by natural killer cells, dendritic cells, and T cells,
confers crucial functions for inducing immunomodulation (such as macrophage activation,
antigen presentation, and helper T cell differentiation), causing antimicrobial (such as
antiviral replication, microbial killing, and MHC induction), and promoting anticancer
activity (such as growth inhibition, cytotoxicity, and immune priming). An emerging type of
immune disorder, called adult-onset immunodeficiency syndrome, has currently reported in
patients who show defects in IFN-γ signaling commonly resulted from the generation of anti-
IFN-γ autoantibody and partly due to mutations in IFN-γ signaling molecules. In these cases,
tuberculosis and non-tuberculosis mycobacteria infection are frequently identified regarding
IFN-γ is potent anti-tuberculosis cytokine. Until now, the detection of anti-IFN-γ
autoantibody is not recurrently in clinical and the immunopathogenesis of anti-IFN-γ
autoantibody remains unclear. This study aims to develop methods for the detection of anti-
IFN-γ autoantibody in patients with adult-onset immunodeficiency and plans to characterize
the immunopathogenic effects of anti-IFN-γ autoantibody. Specific Aim 1 of this study is to
develop methods for detecting anti-IFN-γ autoantibody. ELISA and western blot are utilized
in this study. The possible binding site is next evaluated by using synthetic peptide binding
assay. According to the results, we propose that the generation of anti-IFN-γ autoantibody
may neutralize IFN-γ effectively. Specific Aim 2 is to perform those all functional assay to
check IFN-γ-activated STAT-IRF1 signaling pathway as well as IFN-γ- mediated nitric oxide
generation, cytokine/chemokine production, T cell activation, and anti- tuberculosis activity.
These results provide methods for autoantibody detection and characterize the blockade
effects of autoantibody on IFN-γ signaling and bioactivity.
Keywords: Anti-IFN-γ autoantibody, Adult-onset immunodeficiency syndrome,
Immunopathogenesis, Signaling, Bioactivity


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