The Expression And Significance Of HLA-DR15 In The Patients With Aplastic Anemia,Myelodysplastic Syndrome And Systemic Lupus Erythematosus

Objective:Aplastic anemia(AA) and myelodysplastic syndrome(MDS)are common hematologic diseases.In AA peripheral blood pancytopenia was caused by bone marrow failure and reduction of hematopoietic tissue.In MDS the ineffective hematopoiesis and dysplasia was caused by the abnormal hematopoietic stem cell clone.Although the pathogenesis in both diseases was different,the abnormal immune system was involved in pathogenic process.Clinically,immunosuppressive therapy(IST) is one of the important treatment methods in AA and MDS. Recent studies had found that the expression frequency of human leukocyte antigen DR15(HLA-DR15) was higher in AA,MDS than normal.There was a significant correlation between HLA-DR15 positive and the response to IST.HLA-DR15 positive patients show higher efficiency to IST and more dependence to cyclosporine A(CsA). Systemic lupus erythematosus(SLE) is a chronic systemic autoimmune disease which has a clinical manifestation of multiple system damage. The susceptibility to SLE is related to a number of genes.Abnormal frequency of HLA-Ⅱcategory,HLA-DR2,DR4 were found in SLE.DR2 (HLA-DR15)is a susceptive gene;DR4 is protective gene to SLE.In this study,The expression frequency of HLA-DR15 in patients with AA,MDS and SLE was detected.The control was normal persons and patients with malignant blood tumors.The immunoglobulin levels,T lymphocyte subsets in AA and MDS were also be detected and the relationship with HLA-DR15 was analyzed.IST efficacy of HLA-DR15 positive and negative groups were observed preliminarily to AA and MDS.Methods:The peripheral blood from 28 cases of AA,38 cases of MDS,49 cases of SLE,57 cases of normal persons and 108 cases of blood malignant tumor samples were collected.HLA-DR15 was detected by the technique of PCR-SSP;Immunoglobulin was detected by the method of immune turbidimetry.T cell subsets were detected by Flow cytometry.The basic clinical data and the data of efficacy to IST in AA,MDS patients were collected.Results:①The expression rates of HLA-DR15 in normal control group and the blood malignant tumor group were 24.6%and 26.9% respectively.The difference between the two groups has no significance (P=0.750＞0.05).②The expression rates of HLA-DR15 in AA group was 78.6%. Compared with normal control group the difference was statistically significant(P=0.000＜0.05).OR value was 11.262 and its 95% confidence interval was(3.803,33.350).③The expression rates of HLA-DR15 in MDS group was 63.2%. Compared with normal control group the difference was statistically significant(P=0.001＜0.05).OR value was 4.710 and its 95% confidence interval was(1.940,11.434).④The expression rates of HLA-DR15 in SLE group was 49%. Compared with normal control group the difference was statistically significant(P=0.014＜0.05).OR value was 2.949 and its 95% confidence interval(1.295,6.715).⑤The rates of abnormal level immunoglobulin in AA patients was 28.6%, in which HLA-DR15 positive group was 36.4%and negative group was 0%,the difference between the two groups has no significance(P= 0.310＞0.05).The rates of abnormal T cell subsets was 35.7%,in which HLA-DR15 positive group was 36.4%,33.3%for the negative group,the difference between the two groups has no significance(P＝0.890＞0.05).⑥The rates of abnormal level immunoglobulin in MDS patients was 29.7%,in which HLA-DR15 positive group was 34.8%,21.4%for the negative group,the difference between the two groups has no significance(P=0.382＞0.05).The rates of abnormal T cell subsets was 51.4%,in which HLA-DR15 positive group was 42.9%,64.3%for the negative group,the difference between the two groups has no significance(P=0.102＞0.05).⑦The efficiency of IST to AA patients was 43.8%,in which HLA-DR15 positive group was 53.8%and negative group was 0,the difference between the two groups has statistically significant(P=0.046＜0.05). The efficiency of IST to MDS patients was 37.5%(3/8),in which HLA-DR15 positive group was 50%(1/2)and negative group was 33.3%(2/6),the difference between the two groups has no significance(P =0.676＞0.05).Conclusion:1.The frequency of HLA-DR15 antigen in AA,MDS,SLE patients was significantly higher than that in normal control and the blood malignant tumor patients,statistically the difference is significant. In AA,MDS,SLE group the higher OR values show that there was a positive association between the diseases and HLA-DR15.Since the higher OR value shows the stronger association,the strongest association between the disease and the expression of HLA-DR15 existed in AA patients.HLA-DR15 is susceptibility gene in AA,MDS,SLE.2.It is common that the abnormal level of immunoglobulin and the abnormal T cell subsets in AA and MDS.The abnormal level of immunoglobulin and abnormal T cell subsets were more common in the HLA-DR15 positive group in AA patients.But the difference between the two groups had no statistically significance;the abnormal level of immunoglobulin was more common in HLA-DR15 positive group in MDS,The abnormal T-cell subsets was seen more commonly in negative group,the difference between the two groups showed no statistical significance. 3.The AA patients who taking CsA regularly as IST show good effect,the effect rate in the HLA-DR15 positive group was higher than the negative group.The difference between the two groups had statistically significant.HLA-DR15 may be the predicted gene to the efficiency of IST.In MDS group,the effect rate was no significance between HLA-DR15 positive group and negative.This may be related to the less cases and irregular use of IST.