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Objective To predict the epitopes of Mycobacterium tuberculosis Rv2657c protein, to understand its immunogenicity Methods The T?cell and B?cell epitopes of Mycobacterium tuberculosis Rv2657c protein were predicted by DNAStar software package. The homology of Rv2657c amino acid sequence with the human protein sequences was prepared using Blast method, then the CTL epitopes were predicted using SYFPEITHI supermotif method, BIMAS quantitative motif method and NetCTL prediction method, and the Th epitopes were predicted by RANKPEP and SYFPEITHI supermotif prediction method. Results The prediction using DNAStar software package showed that Rv2657c protein had 5 B?cell epitopes and 6 T?cell epitopes. The protein had 6 CTL epitopes and there were 38 Th epitopes. Conclusion Rv2657c protein has both B?cell epitopes and T?cell epitopes. It may be a candidate target antigen for the studies of vaccine and diagnosis of tuberculosis.
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Objective To study the correlation between genetic polymorphisms of interleukin (IL)-1A/1B and susceptibility to tuberculosis (TB).Methods Genetic polymorphisms of IL-1A and IL1 B in 1032 TB patients and 1008 non-TB patients were analyzed using PCR-MassARRAY method.The correlation between genetic polymorphisms of IL-1A/1B and susceptibility to TB was statistically analyzed.Results Two tag SNPs of IL-1A and three tag SNPs of IL-1B were screened for the study.There were differences in the allele frequencies of rs2853550 and rs3783526 between TB group and non-TB group (P=0.047and P =0.034,respectively).IL-1 B SNP1 rs2853550 (P =0.025,OR =1.302,95 ％ CI =1.034-1.640,TC vs.CC) was found to be highly associated with TB,while the other SNPs showed no significant correlations with TB.Furthermore,IL-1B SNP1 rs2853550 [P=0.019,OR=1.308,95％ CI=1.045-1.638 for (TC+TT) vs.CC] in the dominant model conferred significant risk for TB,but IL-1A SNP2 rs3783526 [P=0.000,OR=0.764,95％ CI =0.591-0.988 for GG vs.(AA+GA)] in the recessive model showed protective effects against TB.The haplotype ‘TG’ in the IL-1B block showed a higher risk for TB compared with the common ‘ CA’ haplotype (P=0.032,OR=1.265,95％ CI=1.020-1.567).The diplotypes containing ‘ GA’ haplotype in IL-1A block and ‘ TG’ haplotype in IL-1B block were major risk factors for TB (for onecopy,adjusted P=0.014,OR=1.403 and 95％ CI=1.072-1.836; adjusted P=0.013,OR=1.339 and 95％ CI=1.063-1.688,respectively),but the diplotype with ‘CG’ in IL-1B block played a protective effect against TB (for two-copy,P=0.006,OR=0.664 and95％ CI=0.494-0.891).Conclusion The genetic polymorphisms of IL-1B rs2853550 might be closely associated with TB,but the GG genotype of IL1 A SNP rs3783526 might have the characteristic of anti-TB.
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Objective To study the relationship between the genetic polymorphisms of carboxylesterase 1 gene (CESI) and the susceptibility to antituberculosis drug-induced hepatotoxicity (ATBDIH).Methods Genetic polymorphisms of CES1 in 473 tuberculosis patients with or without hepatotoxicity (200∶ 273) after antituberculosis chemotherapy were analyzed by PCR-MassArray.Results In4 tags of CES1 single nucleotide polymorphism (SNP),the frequency of the rs1968753 allele had statistical difference between the hepatotoxicity group and the no-hepatotoxicity group ( P =0.0236 ).The characteristics of anti-hepatotoxicity had been shown relationship with rs8192950 ( P =0.044,OR =0.649,95％ CI =0.426-0.989,AC/AA ) and rs1968753 ( P =0.048,OR =0.556,95％ CI =0.311-0.995,GG/AA).The diplotypes with ‘ CGC' haplotype exhibited significant protection against hepatotoxicity at one copy (P=0.048,OR=0.654,95％CI=0.430-0.996).Conclusions The genetic polymorphisms of CESI might have significant association with ATBDIH.SNP rs8192950 AC genotype and rs1968753 GG genotype might be the candidates for risk prediction of ATBDIH.
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Objective To study the therapeutic effects of Ag85A plasmid DNA vaccines in a mouse model of multi-drug resistant-(MDR-) Mycobacterium tuberculosis infection. Methods BALB/c mice were infected with Mycobacterium tuberculosis clinical strain HB361 with isoniazid and rifampin resist-ance by intratail-vein injection and were subsequently divided into 6 groups. At the third day after infection, the mice were treated with saline (group A), vector pVAX1 (greup B), rifampin (group C), vaccae (group D), Ag85A plasmid DNA vaccines (group E),rifampin and Ag85A plasmid DNA vaccines (group F) for 60 d. The lungs and spleens from the mice were taken and their pathological changes, weight and number of myeobacterial colony were examined at the third week after the end of treatment. Results At third week af-ter the end of treatment, the gross pathological observation and histopathological examination in lung showed that the lung lesions were limited, the profile of the alveoli was relatively clear, and normal structure could be seen in 2/3 areas of the lung sections in group D, E and F. The extent of lung lesion was 50% in group D,20% in group E and F. The pathological changes in group A, B, and C were more severer than those in group D, E and F. Compared with group A, the colony-forming units (CFU) in the lungs from mice in group D,E and F decreased 52%, 68%, 78%, respectively. The CFU in the spleens from mice in group D,E and F decreased 48%, 65%, 79%, respectively. Conclusion Ag85A plasmid DNA vaccines alone or Ag85A plasmid DNA vaccines along with chemotherapy have significant therapeutic effects on the mouse model of MDR-Mycobacterium tuberculosis infection.
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Objective To develop a diagnosis model for active pulmonary tuberculosis. Methods The proteomic fingerprinting of 264 sera from active tuberculosis patients and controls were analyzed using the surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS) and protein-chip technology. The peaks were detected and filtrated by Ciphergen PrnteinChip(R) Software (version 3.1.1). Using the Biomarker Pattern 5.0 software, a diagnostic model was developed for diagnosis of active tuberculosis. Re-sults Fifty protein peaks were significantly different between the patients with active pulmonary tuberculosis and the controls with overlapping clinical features (P<0.01). Five protein peaks at 4360, 3311, 8160, 5723, 15173 m/z were chosen for the system classifier and the development of diagnosis model 1. The model differenti-ated the patients with active pulmonary tuberculosis from the controls with a sensitivity of 83.0%, and a speci-ficity of 89.6%. The diagnostic accuracy was up to 86.4%. Three protein peaks at 5643, 4486, 4360 m/z were chosen for the system classifier and the development of diagnosis model 2. The model differentiated the pa-tients with active pulmonary tuberculosis from the controls with a sensitivity of 96.9%, and a specificity of 97.8%. The diagnostic accuracy was up to 97.3%. Conclusion It might be a new diagnostic test for the de-tection of sera from the patients with active pulmonary tuberculosis using SELDI-TOF-MS and protein chip.
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Objective To study the therapeutic effects of Bizhi pills in mycobacterium tuberculosis infection.Methods KunMing mice were infected by intratail-vein injection with mycobacterium tuberculosis H37Rv, then treated with saline(A)or Rifampin(B) or Bizhi pills(C).The lungs,hvers and spleens were taken to observe their pathological changes,weighted and performed mycobacterial culture after 4 months of treatment.Results After 4 months of treatment, indexes of the lung in group C were markedly lower than that in group A (P＜0.05),but higher than that in group B,although the differences were not significant.The lesion of lung in group C were similar as that in group B,and were lessen than that in group A.No obvious lesion of lung was observed in 8 mice of group B and C,but the differences were not significant.Swell of spleen was observed in 9 mice in group A,2 mice in group B and5 mice in group C,the differences were significant(P＜0.01).The numbers of bacteria in the lung and spleen of the female mice of C group were remarkably less than that in group A, and decreased 4 times and 10 times respectively compared with group A(P＜0.01),the numbers of bacteria in the lung and spleen of the male mice of C group were less than that in group A, and decreased 3 times and 2 times respectively.However,the numbers of bacteria in the lung and spleen of the male mice of B group was decreased 14 times and 7 times respectively(P＜0.01).Conclusions The therapeutic efficacy of Bizhi pills in mice with mycobacterium tuberculosis infection is significant, but it is not as good as Rifampin.The therapeutic efficacy of Bizhi pills in female mice of mycobacterium tuberculosis infection is better than that in male mice.