Polymorphisms Of PPE18 And PepA Genes In Mycobacterium Tuberculosis Isolates In Children

Objective: To understand genetic polymorphism of antigens PPE18 and pep A of clinical mycobacterium tuberculosis in children and preliminarily evaluate the influence on the effectiveness of M72 vaccine by studying the effect on T cell epitopes of antigens PPE18 and pep A.Methods: 168 mycobacterium tuberculosis isolates were selected from the infection department of Children’s hospital of Chongqing from 2006 to 2013, and amplified PPE18 and pep A genes by PCR reaction. Both the gene polymorphism analysis and the T cell epitopes polymorphism analysis were based on the results of sequence comparison between amplified products and H37 Rv sequence. Among the 168 isolates, the differences in gene polymorphism between Beijing family and non-Beijing family isolates were tested by statistical method.Results: Of the 168 isolates, 117(69.64%) isolates showed PPE18 gene polymorphisms, and 110(65.48%) isolates resulted in PPE18 antigen amino acid changes; 6(3.6%) isolates showed pepA gene polymorphism, and 2(1.2%) isolates led to pepA antigen an amino acid change. The mutation rate of PPE18 protein in Beijing family isolates is significantly higher than non-Beijing family isolates; although the mutation rate of pep A protein is higher than non-Beijing family isolates, but without statistical difference.Conclusion: Both antigen PPE18 and pepA showed polymorphism among clinical isolates mycobacterium tuberculosis in children, which may lead to significantly change of protein function. The T cell epitopes of PPE18 protein is changeful, which may be a way for mycobacterium tuberculosis to escape immune response, and it implied that the protective effect induced by M72 vaccine may not satisfied for a proportion of mycobacterium tuberculosis isolates present in the natural population, especially isolates belonging to Beijing family.