Objective: To evaluate the clinical implication of combined measurement of bone marrow (BM) T lymphocyte intracellular IFNgamma with HLA-DRB1*1501 in predicting the response to immunosuppressive therapy (IST) in patients with aplastic anemia (AA).
Methods: Enrolled into the present study were 51 idiopathic AA patients treated with cyclosporine A (CsA) based IST. BM CD(8)(+) T lymphocyte intracellular IFNgamma was determined with flow cytometry and HLA-DRB1*1501 detected with PCR-sequence specific primer before treatment. The relationship between laboratory indices and clinical response were investigated and the potential usefulness of parameters in predicting the response to IST for AA was evaluated.
Results: These HLA-DRB1*1501 shows sensitivity of 45.7% (16/35) and specificity of 87.5% (14/16) respectively. Intracellular IFNgamma has sensitivity of 94.3% (33/35) and specificity of 62.5% (10/16), respectively. With combination of intracellular IFNgamma with HLA-DRB1*1501, the parallel test increases the sensitivity of 97.1% (34/35) and the negative predictive value of 90.0% (9/10). On the other hand, the serial test improves the specificity and positive predictive value which both achieve 93.7% (15/16). It could be calculated through a logistic regression equation that the probabilities of prediction of four subgroups of patients whose results are both positive reaction, a positive intracellular IFNgamma plus negative HLA-DRB1*1501, a negative intracellular IFNgamma plus positive HLA-DRB1*1501 and both negative reaction are 89.0%, 77.4%, 34.5% and 18.2%, respectively.
Conclusions: Combination of BM T cells intracellular IFNgamma stain and HLA-DRB1*1501 phenotype can be a useful predictor for AA patients in immunosuppressive therapy. The patients with both positive results of the two tests may have more possibilities to response to IST. It may have an important implication for the majority of AA patients whose intracellular IFNgamma stain has a positive reaction.