Serra-Vidal Mᵃdel Mar, Latorre Irene, Franken Kees L C M, Díaz Jéssica, de Souza-Galvão Maria Luiza, Casas Irma, Maldonado José, Milà Cèlia, Solsona Jordi, Jimenez-Fuentes M Ángeles, Altet Neus, Lacoma Alícia, Ruiz-Manzano Juan, Ausina Vicente, Prat Cristina, Ottenhoff Tom H M, Domínguez José
Department of Microbiology, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Hospital Universitari Germans Trias i Pujol Badalona, Spain ; Department of Genetics and Microbiology, Universitat Autònoma de Barcelona Bellaterra, Spain ; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III Badalona, Spain.
Department of Immunohematology and Blood Transfusion/Department of Infectious Diseases, Leiden University Medical Center Leiden, Netherlands.
Front Microbiol. 2014 Oct 8;5:517. doi: 10.3389/fmicb.2014.00517. eCollection 2014.
The aim of our work here was to evaluate the immunogenicity of 60 mycobacterial antigens, some of which have not been previously assessed, notably a novel series of in vivo-expressed Mycobacterium tuberculosis (IVE-TB) antigens. We enrolled 505 subjects and separated them in individuals with and without latent tuberculosis infection (LTBI) vs. patients with active tuberculosis (TB). Following an overnight and 7 days stimulation of whole blood with purified recombinant M. tuberculosis antigens, interferon-γ (IFN-γ) levels were determined by ELISA. Several antigens could statistically significantly differentiate the groups of individuals. We obtained promising antigens from all studied antigen groups [dormancy survival regulon (DosR regulon) encoded antigens; resuscitation-promoting factors (Rpf) antigens; IVE-TB antigens; reactivation associated antigens]. Rv1733, which is a probable conserved transmembrane protein encoded in DosR regulon, turned out to be very immunogenic and able to discriminate between the three defined TB status, thus considered a candidate biomarker. Rv2389 and Rv2435n, belonging to Rpf family and IVE-TB group of antigens, respectively, also stood out as LTBI biomarkers. Although more studies are needed to support our findings, the combined use of these antigens would be an interesting approach to TB immunodiagnosis candidates.
我们在此开展这项工作的目的是评估60种分枝杆菌抗原的免疫原性，其中一些抗原此前尚未得到评估，特别是一系列新型的体内表达的结核分枝杆菌（IVE-TB）抗原。我们招募了505名受试者，并将他们分为潜伏性结核感染（LTBI）阳性和阴性个体以及活动性结核病（TB）患者。在用纯化的重组结核分枝杆菌抗原对全血进行过夜和7天刺激后，通过酶联免疫吸附测定（ELISA）法测定干扰素-γ（IFN-γ）水平。几种抗原在统计学上能够显著区分不同个体组。我们从所有研究的抗原组中获得了有前景的抗原[休眠生存调节子（DosR调节子）编码的抗原；复苏促进因子（Rpf）抗原；IVE-TB抗原；再激活相关抗原]。Rv1733是一种可能由DosR调节子编码的保守跨膜蛋白，结果显示其具有很强的免疫原性，并且能够区分三种确定的结核病状态，因此被视为一种候选生物标志物。分别属于Rpf家族和IVE-TB抗原组的Rv2389和Rv2435n，也作为LTBI生物标志物脱颖而出。尽管需要更多研究来支持我们的发现，但联合使用这些抗原将是一种用于结核病免疫诊断候选物的有趣方法。
