A point-of-care (POC) test that could be implemented at peripheral levels of the health system in low-income countries has been predicted to reduce tuberculosis (TB)-related mortality by one-third. However, no truly POC test is in the diagnostic pipeline. For maximum impact, a POC test should have high specificity such that a positive test result can be followed by the immediate initiation of treatment. However, a highly sensitive but less specific POC test is a more realistic short-term goal and could be used as an important screening tool in peripheral health care settings ? a negative result would effectively rule-out active TB and a positive result would initiate referral for further testing. Thus, as a first step toward the development of a POC rule-out test, our objective is to identify immunologic biomarkers that are highly sensitive for active TB in HIV-infected TB suspects. To address this objective, we will conduct a nested case-control study using clinical data and banked blood samples from an NHLBI-funded study of HIV-infected TB suspects at Mulago Hospital (Kampala, Uganda). We will measure antibody responses to at least 28 Mycobacterium tuberculosis proteins and levels of up to 48 chemokines/cytokines in plasma of 100 TB cases and 100 age-, gender-, and CD4 stratum-matched controls using Luminex-based multiplex assays. We will use logistic regression and novel classification algorithms to identify antibody and cytokine/chemokine response profiles predictive of TB status. We anticipate that data collection and analysis will be completed in 8-10 months, and will provide critical pilot data for an R01 application to further validate promising biomarker profiles and to evaluate their clinical impact.