Research Of Combined Measurement HLA-DRB1~*1501 And TNF-α-308 Gene Polymorphism In Predicting The Response To Immunosuppressive Therapy For Aplastic Anemia

Objective:To investigate the correlation of phenotype of HLA-DRB1*1501 and the polymorphism of tumor necrosis factor-a(TNF-a)-308G/A gene with response to immunosuppressive therapy (IST)based on the principle of CsA for aplastic anemia(AA). To evaluate the potential value of combination of HLA-DRB1*1501 and TNF-α-308 gene polymorphism detection in predicting response to IST in patient with aplastic anemia.Materials and Metheods:1 Fouty newly dianosed AA patients were treated with IST based on the principle of CsA, consisting of 18 famales and 22 males with median age of 36(range 11-79 years).31 cases were severe AA(SAA) and 9 cases were non-severe AA(NSAA).The treatment effect were determined in 3-6 months.2 The polymorphisms of TNF-a-308G/A were examined by PCR-RFLP.3 Phenotypes of HLA-DRB1*1501 were determind by PCR-SSP.4 The relaton between laboratoy indices and clinical response were investigated to compare the difference with these parameters in patients with different responses to IST. To evaluate the potential value of combination of HLA-DRB1*1501 and TNF-α-308 gene polymorphism detection in predicting response to IST in patient with aplastic anemia.Results 114 of HLA-DRB1*1501 genotypes were detected in 40 AA patients, frequency of phenotype was 35%(14/40) and frequency of genotype was 19.4%. The frequency of phenotype and genotype in AA patients were observably higher than in healthy people. The frequencies of phenotype of HLA-DRB1*1501 were 50% and 12.5% respectively in patients with IST treatment effectively and ineffectively, and the frequencies of genotypes of HLA-DRB1*1501 were 29.3% and 6.46% respectively. There is a observable difference in two groups.12 AA patients were treated effectively with IST in 14 HLA-DRB1*1501 positive patients and the effective rate was 85.7%,12 patients were treated effectively with IST in 26 HLA-DRB1*1501 negative patients and the effective rate was 46.2%, The distinction had statistical significance.213 of TNF-α308A genotypes were detected in 40 AA patients, frequency of phenotype was 32.5%(13/40) and frequency of genotype was 17.8%. The frequency of phenotype and genotype in AA patients were observably higher than in healthy people. The frequencies of phenotype of TNF-a 308A were 45.8% and 12.5% respectively in patients with IST treatment effectively and ineffectively, and the frequencies of genotypes of TNF-a 308A were 26.4% and 6.46% respectively. There is a observable difference in two groups.11 AA patients were treated effectively with IST in 13 TNF-a 308A positive patients and the effective rate was 84.6%,13 patients were treated effectively with IST in 27 TNF-a 308A negative patients and the effective rate was 48.1%, The distinction had statistical significance.3 The potential value of combination of HLA-DRB1*1501 and TNF-α-308 gene polymorphism detection in predicting response to IST were evaluated by Logistic regression equation and ROC curve analysis. The predictive probabilities of 0.963,0.785,0.754 and 0.354 were calculated from Logistic regression equation for four groups of patients as follows:positive for both reaction, positive HLA-DRB1*1501 and negative TNF2, negative HLA-DRB1*1501 and positive TNF2 and negative for both reaction, respectively. So the predictive probabilities of positive for both reaction, positive HLA-DRB1*1501 and negative TNF2, negative HLA-DRB1*1501 and positive TNF2 were greater than cutoff point (P=0.6778). And the predictive probabilities of positive for both reaction was above positive HLA-DRB1*1501 and negative TNF2, negative HLA-DRB1*1501 and positive TNF2. They suggested that treatment effects were better of patients with positive for both reaction than positive HLA-DRB1*1501 and negative TNF2, negative HLA-DRB1*1501 and positive TNF2. The predictive probabilities of negative for both reaction was less than cutoff point suggesting patients with negative for both reaction canot react excellent to IST possibly.Conclusion:1 This study investigated and evaluated certain predicts which seemed to be of potential predictive value. It is confirmed that genetic parameters are essential to predict response to IST for AA patient.2 Combination of HLA-DRB1*1501 gene phenotype and TNF-α-308 gene polymorphisms can be a useful predictor for AA patient treated with IST. Superior to each of the single test, the combination shows a greatly improved sensitivity3 Patients with positive for both reaction, positive HLA-DRB1*1501 and negative TNF2, negative HLA-DRB1*1501 and positive TNF2 are indicated good response to IST and the former being of a superior predictive power over the latter two. Patients with negative HLA-DRB1*1501 and negative TNF2 may predicts a bed outcome of treatment, suggesting clinician to select other immunosuppressive therapy or other therapeutic method.4 Both tests are well established in methodology, simple and time-saving to be performed. Combination of this two parameters provides physicians with a quick judgment for patient'possible response to treatment and provides a effective and convenient method to predict response to IST for clinician.