Synthesis of covalent conjugates of hexaarabinofuranoside with proteins and their testing as antigens for serodiagnosis of tuberculosis

摘要

Specificity and sensitivity are crucial in diagnosis of tuberculosis. An insufficiently sensitive method will "miss" too many persons really sick with active tuberculosis. If the method is insufficiently specific, its use will give many false positive results among healthy people or among non-tubercular patients (the latter fact is not too critical for mass screening of population, because the primary diagnosis is always checked by alternative methods). Enzyme-linked immunosorbent analysis (ELISA), immunochro-matography (IC), and dot-blotting technique using one or several recombinant protein antigens of Mycobacterium tuberculosis were developed in the recent time for serodiagnosis of tuberculosis. In particular, an array of recombinant antigens (38-, 63-, 64-, 14-, and 59-kDa) is successfully used in commercial serological assays TB-DOT (Upper Bio-tech, China, http://www.poct.cn) and TB-Check-1 (VEDA.LAB, France, http://www.vedalab.com); the declared assay specificity reaches 99.42%, and the sensitivity is 98.52% (see Ref. 1). However, it was found when using these tests that this level of sensitivity is reached only for certain human populations, which can be associated with national and ethnic peculiarities of the humoral immune response to tuberculosis.For example, 11 recombinant proteins of M. tuberculosis have earlier been obtained and used as antigens for the analysis of 320 sera of sick and healthy peoples from the central region of Russia. None of them provided the sensitivity higher than 55%, and various combinations of antigens increased this parameter by at most 7 %.