Local Immune Responses in Atypical Pulmonary Tuberculosis among Tanzanian AIDS Patients

Gibson S. Kibiki, Clement F. Kalambo, Suzanne E. Stroup, and Eric R. Houpt (2006) CHEST,
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PURPOSE: It is well established that the clinical and radiographic presentation of Tb in the setting of HIV/AIDS can become atypical however the immune features associated with this change are unclear. METHODS: We performed bronchoscopy on 55 HIV patients in Tanzania with no clear diagnosis and abnormal chest radiographs. BAL fluid was tested for tuberculosis by culture, DNA probe, and PCR and also tested for 23 cytokines and chemokines by Luminex assay. RESULTS: Thirteen (24%) were found to have Tb based on culture, DNA probe, and PCR of BAL fluid. Among these 13 HIV+/Tb+ cases, CD4 count positively correlated with the extent of cavitary disease (measured radiographically) as well as Tb burden in BAL fluid (real-time PCR Ct). HIV+/Tb+ patients revealed higher BAL RANTES, GM-CSF, and IP-10 levels than the 22 HIV+/Tb- patients assayed (49.54 ± 7.97 vs. 30.78 ± 3.21, 10.29 ± 1.44 vs. 5.11 ± 0.99, and 977 ± 341 vs. 293 ± 73 pg cytokine/mg BAL protein, respectively P < 0.05). BAL TGF-B1 correlated negatively with the extent of chest disease as quantified radiographically (CXR score 0-18, R = -0.57, P < 0.05). Finally, patients with non-cavitary Tb had higher BAL IL-7, IL-6, and IP-10 than those with cavitary tuberculosis (n = 7 and 6, respectively, P < 0.05). Other cytokines/chemokines exhibited no statistical correlations with CD4 count, radiographic findings, or Tuberculosis. CONCLUSION: These data from sub-Saharan Africa suggest HIV-associated Tb and the loss of cavitation seen with advanced AIDS exhibit distinct immunological features. CLINICAL IMPLICATIONS: The findings may have implications for understanding the co-pathogenesis of HIV/Tb (e.g., elevated RANTES may favor transmission of CXCR4 virus) as well as that of the atypical Tb observed in the setting of advanced AIDS (e.g., marked by augmentation of the T cell chemokine IP-10).