The effects of BAFF and BAFF-R-Fc fusion protein in immune thrombocytopenia.
Elevated level of B-cell activating factor (BAFF) has been implicated in the pathogenesis of some autoimmune diseases. Blockade of receptor and ligand binding by decoy receptor has demonstrated a clinical benefit in both oncologic and immunologic diseases. In this report, we have detected plasma BAFF and BAFF mRNA expression in immune thrombocytopenia (ITP) patients by enzyme-linked immunosorbent assay (ELISA) and real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR). The effects of recombinant human BAFF (rhBAFF) and BAFF-R-Fc fusion protein (BR3-Fc) on B cells, T cells, platelets, secretion of interferon gamma (IFNgamma), and interleukin-4 (IL-4) were measured by flow cytometry and ELISA. Patients with active disease had higher levels of plasma BAFF and BAFF mRNA than patients in remission and controls. In in vitro assays, rhBAFF promoted the survival of CD19(+) and CD8(+) cells, and increased the apoptosis of platelets and the secretion of IFN-gamma. BR3-Fc successfully corrected the effects of rhBAFF on lymphocytes, platelets, and cytokines. These findings suggest that BAFF may play a pathogenic role in ITP by promoting the survival of CD19(+) and CD8(+) cells, and increasing the apoptosis of platelets and the secretion of IFN-gamma. Blockade of BAFF by BR3-Fc might be a promising therapeutic approach for ITP.
Zhu
Xiao-juan
XJ
Hematology Oncology Centre, Qilu Hospital, Shandong University, Jinan, Republic of China.
Shi
Yan
Y
Peng
Jun
J
Guo
Cheng-shan
CS
Shan
Ning-ning
NN
Qin
Ping
P
Ji
Xue-bin
XB
Hou
Ming
M
D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D053264:B-Cell Activating Factor / Q000276:immunology / Q000378:metabolism*; D053265:B-Cell Activation Factor Receptor / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects; D015847:Interleukin-4 / Q000096:biosynthesis; D008297:Male; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D007141:Immunoglobulin Fc Fragments; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C505719:TNFSF13B protein, human; D015847:Interleukin-4; D007371:Interferon-gamma