The Study Of T Lymphocyte Activation And CD55~-CD59~- Blood Cells In Patients With Aplastic Anemia Accepted Inimmunosuppressive Therapy

Objective:More and more studies had indicated that pathogenesy of aplastic anemia concerned with an disorder of T cellular immunity. Immunosuppressive therapy(IST) is the standard approach to treat in acquired aplastic anemia(AA).A good many of patients had achieved remission or improvement by using IST.Otherwise,one third of AA patients had treatment futility.We studied some immune index,such as the index about Lymphocyte Activation,minim CD55^- CD59^- blood cells.We trid to find out some connection between those idex and Immunosuppressive therapy and investigated the latent value of predicting curative effect about IST.Subject and method:31 AA patients(male/female:18/13),aged 12-76 year.(median 36 year),accepted from Jun.2007-Jul.2008 were studied and tested for immunosuppressive therapy(mainly with cyclosporin,5mg/kg/d) for at least 6 months,observation continued to the 6_th month if the treatment is ineffective in the first three months,after which the ineffectiveness shall be deemed a failure.CD3⁺, CD4⁺ and CD8⁺ immunocyte and CD55^- CD59^- granular cell,CD55^- CD59^-akaryocyte as shall be counted by flow cytometry(with determination of IFN-γand IL-4 expression in CD4⁺ and CD8⁺ immunocyte) prior to treatment of the patient with aplastic anemia.Comparison study of the indicators and the variance in patient recovery as documented in follow-ups.Screening of meaningful indicator of therapeutic effect based on in cross sectional study and ROC curve was conducted to evaluate the clinical prospective of the predictive indicators.Result:1.Normal CD3⁺ cell count in peripheral blood mononuclear cells in AA patients,CD3⁺ CD4⁺ cell count decreasing(P=-0.034),CD3⁺ CD8⁺ significantly increasing(P=0.005) and CD4+/CD8+ratio lowered(P=0.003) as compared with the control group for significance.The patients were then divided into 3 immune groups:The groupâ… :CD4⁺/CD8⁺ ratio≤1;The groupâ…¡:CD4⁺/CD8⁺ratio＞1 but＜2;The groupâ…¢:CD4⁺/CD8⁺ ratio≥2.Effectiveness ratio of combined immunosuppressive therapy:The groupâ… vs.The groupâ…¡(P=0.002) and The groupâ… +The groupâ…¢vs.The groupâ…¡(P=0.003) resulted in significant difference,as apposed to the result of The groupâ… vs.The groupâ…¢(P=0.137) and The groupâ…¡vs. The groupâ…¢(P=0.242).2.Increased proportion of CD55^- CD59^- cell counts with statistic significance(P＜0.05).The increase in PHN-type cell counts was dominated by CD55^- CD59^- gannual cells but the PNH⁺ patients(80.0%8/10) had no better results after the treatment course than its negative counterparts(52.4%11/21).3.the patient PBMNC registered higher Th1 and Tcl cell counts than control.Patient with positive IFN-γdetection in CD8⁺ cells resulted better than its negative counterparts after the treatment course(P＜0.001).4.Assessment of predictability with the indicators based on cross-sectional study:peak sensitivity(95.6%) and accuracy (82.9%) was found in IFN-γpositive detection with lowest specificity(60.0%);best specificity(83.3%) was found in PNH cell positive detection,but with weak sensitivity(42.1%) and accuracy(58.1%).5.ROC curve analysis:IFN-γlevel in CD8⁺ cells count toped in area curve(0.812),followed by IFN-γlevel in CD4⁺ cells(0.811).Conclusion:the study was aimed at determining the feasibility of applying the immune-related indicators to the outcome prediction of the IST in the very beginning of diagnosis,so as to guide the proper choice of clinical treatment. AA patients has higher proportion of CD3⁺ and CD8⁺ T cells and lower proportion of CD4⁺/CD8⁺ cells in total lymph cells in peripheral blood,as compared with the control group,indicating the involvement of CD8⁺ cells in the mechanism of pathogenesis.Further analysis of the three immune The groups for the IST outcome found significant difference in The groupâ… vs.The groupâ…¡and The groupâ… +The groupâ…¢vs.The groupâ…¡as apposed to the result of The groupâ… vs.The groupâ…¢and The groupâ…¡vs.The groupâ…¢,indicating only the cases with abnormity found by immunoassay(esp.CD4⁺/CD8⁺ inversion) achieves good outcome of the combined immunosuppressive therapy.32.7%(16/49) cases were detected of PNH-type cells.Although had the higher remission rate,the positive ones had no better result than the negative ones in the IS therapy.This result maybe concerned with the less cases.Unbalance Tc1/Tc2 and Th1/Th2 ratios were found in the AA patients:their Th1 and Tc1 counts were significantly higher than health subject.Those with positive detection of IFN-γin CD8⁺ cells had significant better outcome than their negative counterparts.Screening of meaningful indicator of therapeutic effect based on in cross-sectional study and ROC curve to evaluate the clinical prospective of the predictive indicators resulted in most significance found in the positive detection of IFN-γin CD8⁺ cells as the predictive indicator of therapeutic effect,which had the highest sensitivity and accuracy but weak specificity,thus prone to misdiagnosis. Therefore single indicator(no matter which) does not meet the requirement in the outcome prediction of IST,while a combination of the effective ones shall maybe exploited in guiding to a better solution in the clinical practice.