| ObjectivesThe study was to investigate the changing patterns of the immune and hematopoietic functionalities of the severe aplastic anemia(SAA) patients with complete remission(CR) after treated with immunosuppressive therapy(IST), evaluating the correlations among the immune parameters as well as the immune and hematopoietic parameters. These results can be leveraged as the theoretical base for establishing scientific and effective AA treatment plans and early judgment of prognosis of SAA patients.At the same time, select the newly diagnosed SAA patients with combined CMV, parvovirus B19 and EB virus infection, analyze the change of the immune parameters and compare with those from the non-infected SAA patients. This help to draw conclusions of the effect of virus infection on the immune functionalities and effectiveness of the treatments for the SAA patients.MethodologyThe SAS patients studied in this research were treated in the Hematology Department of Tianjin Medical University General Hospital from October 2004 to July 2014. They were both newly diagnosed patients and patients in the recovery stage after treated with IST.Part One: A total of 31 SAA patients, who had achieved complete remission(CR), had been studied for up to 3 years IST. Their immune and hematopoietic functionality changes had been evaluated at 0, 0.5, 1, 2, and 3 year(s) IST. The immune functionality parameters monitored included the CD3+CD4+ to CD3+CD8+ ratio, Th1 to Th2 ratio, myeloid dendritic cell(m DC) to plasmacytoid dendritic cell(p DC) ratio, as well as CD8+HLA-DR+ percentage. The hematopoietic functionality parameters included peripheral blood cell counts and bone marrow assay. A cohort study was performed on these parameters in order to find the changing patterns of the parameters during treatment.Part Two: A total of 56 SAA patients with combined CMV, parvovirus B19 and EB virus infection had been studied. The percentages and ratios of the T-cell subset, Th subset, DC subset, the activated T-cell subset and NK cell subset had been analyzed.These results had been compared with those of the SAA patients(a total 96 cases) who did not have virus infection. The effectiveness of IST for patients with and without virus infection has been studied.ResultsPart One The CD3+CD4+/CD3+CD8+ ratio for the SAA patients at 0, 0.5, 1, 2, 3 years IST were 0.34±0.21, 0.60±0.4, 0.62±0.41, 0.85±0.45, and 0.94±0.34 respectively. The increased ratio after 1 year IST was of statistical significance and the ratio continued to climb at 3 years IST(P < 0.05). The Th1/Th2 ratio at 0, 0.5, 1, 2, 3 year(s) IST were 12.54±11.55, 3.15±1.95, 2.15±2.11, 2.64±2.55, and 2.20±1.36 respectively. The decreased ratio after 6 months was of statistical significance and the ratio kept decreasing afterwards. The m DC/p DC ratio was 0.88±1.06 at 3 years IST, which is significantly lower than that of untreated patients(2.67±3.44 with P < 0.05); the CD8+HLA-DR+ ratio was 42.05±26.85, 19.24±15.41, 20.67±9.93, and 15.94±8.58 at 0, 0.5, 1, 2, 3 year(s) IST. The decreased ratio at six months post-IST had statistical significance. Furthermore, it continued to decrease in the follow-up measurements(P < 0.05). Among the hematopoietic parameters, the peripheral blood neutrophilis count, reticulocyte count, bone marrow granulocytes ratio, and bone marrow megakaryocyte count all increased apparently at 0.5 IST(P < 0.05). The ratio of bone marrow erythroid cells also increased apparently at 1 year IST, compared to that of untreated patients. The ratios of m DC/p DC and Th1/Th2 exhibit positive correlation(P<0.05). The percentage of CD8+HLA-DR+ and quantity of peripheral blood neutrophilis showed inverse correlation(P < 0.05).Part Two When compared with patients without virus infection, the SAA patients with CMV-Ig M, parvovirus B19-Ig M and EB virus infection had increased CD8+ T cell percentage. Furthermore, the absolute value of CD8+T cell had increased as well. The CD4/CD8+ T cell ratios for all three groups had decreased. Among them, the CMV-Ig M and parvovirus B19-Ig M groups also showed decreased percentage of CD4+ T cell(P < 0.05). The percentages of the CD8+HLA-DR+/CD8+T for all three groups had increased. Moreover, the CD4+HLA-DR+/CD8+HLADR+ percentages for the CMV-Ig M and parvovirus B19-Ig M groups had both decreased and CD4+HLA-DR+/CD4+ T cell for theparvovirus B19-Ig M group had decreased as well(P < 0.05). When compared with patients without virus infection, the SAA patients with combined parvovirus B19-Ig M infection exhibit increased Th1 percentage(P < 0.05) as well as increased p DC percentage(P < 0.05). Patients infected with EB virus showed lower NK cell percentage. Three years after IST, the treatment is significantly less effective for the SAA patients with combined virus infection than those without.ConclusionsPart One For the SAA patients who responded well(CR) to IST, improvements in peripheral neutrophilis and bone marrow myeloid cells were first observed. They further revealed improvements in the CD8+HLA-DR+ percentage, Th1/Th2 ratio, CD3+CD4+/CD3+CD8+ ratio, along with m DC/p DC ratio during IST. Moreover, the recoveries of immune parameters and hematopoietic parameters were correlated, suggesting IST prompted improvements of patients’ immune functionalities, which is the pivotal factor for the SAA patients to achieve CR.Part Two CMV, parvovirus B19 and EB virus infection worsen the immune functionality abnormality of the newly diagnosed SAA patients. Compared with patients who did not have virus infection, the efficiency of IST had significantly reduced. |
PDF Full Text Request