International Research in Thailand

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This past year we have opened, enrolled, and closed our study to new enrollment because we reached our total enrollment target in 6 months. We enrolled 212 patients into five groups, including those with severe opportunistic infections, patients with pulmonary tuberculosis, patients with disseminated tuberculosis, and normals. We have performed in-depth analysis of the plasma from these patients looking for autoantibodies to 41 different cytokines. The only anticytokine autoantibody that was associated with opportunistic infection was the anti-interferon gamma autoantibody, which was found in approximately 90% of those with severe opportunistic infections. All these patients were HIV uninfected and had no other recognized cause of immune dysfunction. Interestingly, those with pulmonary tuberculosis and those with disseminated tuberculosis did not have significant levels of anti-interferon gamma autoantibodies. These results were highly statistically significant. Importantly, the entire defect in those with opportunistic infections seems to be in the plasma component, since when those patients cells were washed clean of their own plasma, their function as normal. Further, addition of inhibitory plasma to normal cells fully recapitulated the defect in vitro. Therefore, we have shown in a large cohort of patients in Thailand and Taiwan with severe opportunistic infections, including nontuberculous mycobacteria, that autoantibodies to interferon gamma account for the defect and reproduce a state of severe immunodeficiency. As a result of this project and in order to extend these diagnostic opportunities to the field, we have developed a simple screening assay for anti-interferon gamma autoantibodies that will allow us to identify, follow, and titer activity.