THE PYRUVATE DEHYDROGENASE E1 SUBUNIT RV2241 (ACEE) OF MYCOBACTERIUM TUBERCULOSIS IS DIFFERENTIALLY EXPRESSED IN LOCAL CLINICAL ISOLATES AND IS IMMUNOGENIC IN PULMONARY TUBERCULOSIS PATIENTS

SCHIERLOH P; KLEPP L; GARCÍA M; VAZQUEZ C

Mar del Plata

Congreso; LXII Reunión Anual de la Sociedad Argentina de Inmunología; 2014

Sociedad Argentina de Inmunología (SAI)

Mycobacterium tuberculosis (Mtb), formerly regarded as highly conserved specie, displays a considerable degree of genetic variability that can influence the outcome of the disease as well as the innate and adaptive immune response. By proteomic approaches we searched for proteins that were differentially expressed between two local clinical isolates, one from Latin-American-Mediterranean (LAM) and other from Harlem (H) lineages. In order to analyze the immunogenic ability of differentially expressed proteins, we cloned and produced recombinant fusion proteins and tested specific antibody and cell mediated immune responses in TB patient samples (n=40). Besides, we applied a battery of immunoinformatic tools in order to contrast our experimental results. We identified seven differentially expressed proteins that were confirmed at transcriptional level. Four of these proteins were successfully cloned: Rv2241, Rv0009, Rv0407 and Rv2624c. We found that all these proteins are able to induce humoral and T-cell mediated IFN-γ (IGRA) responses in patients with drug-sensitive and drug-resistant tuberculosis. However, ROC analysis indicates that only anti-Rv2241 serological response exhibits considerable potential as TB biomarker (Area under ROC 85%, p 0.001). Consistently, bioinformatics predictions confirmed that Rv2241 exhibits higher immunogenic potential at the level of linear B-cell epitopes (p 0.01), conformational B cell epitopes (p 0.05) and MHC-I and MHC-II binding peptides (p 0.01) compared with the other three proteins. Herein we identified a new Mtb-antigen that is differentially expressed in a local clinical isolate and that induces an antibody response with potential as disease biomarker.