ABSTRACT
In recent decades, the treatment of autoimmune diseases has moved from the use of hormones and conventional immunosuppressive drugs to biological agents. B cell proliferation and maturation play crucial roles in the development of autoimmune diseases. The tumor necrosis factor superfamily ligand B cell activating factor (BAFF) and its receptor mediate B cell survival through regulating signaling pathways. Therefore, BAFF and its receptors are important therapeutic targets for the treatment of autoimmune diseases. This review describes the mechanism of BAFF and its receptor in the human body system and introduces the latest views on how over-activation of BAFF pathway promotes the development of autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, and rheumatoid arthritis. In connection to the treatment of the above three diseases, this review discusses the clinical trials and application status of three BAFF-targeting antibody drugs, including Belimumab, Tabalumab and Atacicept. Finally, this review proposes new strategies that targeting the BAFF pathway to provide a new treatment for autoimmune diseases.
Subject(s)
Humans , Autoimmune Diseases/drug therapy , B-Cell Activating Factor/therapeutic use , B-Lymphocytes , Interleukin-4 , Lupus Erythematosus, Systemic/drug therapyABSTRACT
Objective@#To evaluate the efficacy and prognostic factors in core binding factor (CBF) acute myeloid leukemia (AML) under current therapy modalities, therefore optimizing the treatment strategies.@*Methods@#Standard cytological and immune methods including next generation sequencing (NGS) were used for risk stratification. Complete remission (CR) rate, disease-free survival (DFS) and overall survival (OS) were assessed by multivariate Logistic and Cox regression models in a total of 206 adults (aged 16-65 years) with CBF-AML, including 152 AML patients with t(8;21) and 54 with inv(16).@*Results@#The CR rate of inv(16) patients after first course was 54/54(100%), significantly higher than that of t(8;21) patients [127/147(86.4%), P=0.005]. The fusion transcript level and KIT mutation were independent factors related to CR rate in t(8;21) patients (P=0.044 and 0.027; respectively). DFS and OS in inv(16) patients tended to be more superior than that in t(8;21) patients (P=0.066 for DFS; P=0.306 for OS; respectively). Multivariate Cox identified negative expression of CD19 and female gender the independent predictors of inferior DFS in t(8;21) patients (P=0.000 for CD19; P=0.006 for sex; respectively). Analysis of combining CD19 with gender indicated that females/CD19-subpopulation had significantly poor DFS than did males/CD19+ ones (Bonferroni-P<0.000 01). The number of mutations in each patient, FLT3-ITD and additional karyotype abnormalities did not affect CR rate and DFS (all P>0.05).@*Conclusions@#Patients with inv(16) have better induction response than those with t(8;21). High level of fusion transcripts and positive KIT mutation are associated with low CR rate in t(8;21) patients. Negative CD19 expression and female gender are independent predictors of inferior DFS in t(8;21) patients.
ABSTRACT
Objective To investigate the significance of serum CD25 / serum ferritin in the diagnosis of lymphoma-associated hemophagocytic syndrome (LAHS),so as to provide the clinical basis for improving its recognition and giving effective therapy. Methods The serums were collected from 70 patients with hemophagocytic syndrom in Beijing Friendship Hospital, Capital Medical University during the period from October 2008 to June 2011, including 31 LAHS cases and 39 other disease-associated HPS cases. The serum CD25 level in HPS patients was measured with enzyme-linked immunosorbent assay (ELISA), and the serum ferritin was measured on the same day. Then the serum CD25/ferritin ratio was calculated and the differences of the serum CD25, serum ferritin and serum CD25/ferritin ratio between two groups were compared. Results The variance of serum CD25 [(15760.52±7851.74) pg/ml vs (12727.41±11285.28) pg/ml,t=-1.78,P=0.075] and serum ferritin levels (1750.00 ng/ml vs 2947.00 ng/ml,Z=-1.490,P=0.136)were not statistically significant between two groups,while the serum CD25/serum ferritin ratio in LAHS patients was significantly higher than the other group(8.57×10-3 vs 2.84×10-3,Z=-2.106,P=0.035).Conclusion The serum CD25/ serum ferritin ratio is statistically higher in LAHS patients, which might be a novel useful marker for predicting underlying malignant lymphoma in HPS patients.