کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6062922 | 1201845 | 2016 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Interfering with baffled BÂ cells at the lupus tollway: Promises, successes, and failed expectations
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
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چکیده انگلیسی
B cells play an important role in systemic lupus erythematosus by acting not only as precursors of autoantibody-producing cells but also as antigen-presenting, cytokine-secreting, and regulatory cells. Unopposed activation of B cells through their B-cell receptor for antigen, as seen in B cells lacking Lyn kinase, results in systemic autoimmunity. The B-cell activating factor of the TNF family (BAFF), nucleic acid-sensing Toll-like receptors (TLRs), and type I interferon can affect B-cell survival and decrease their threshold for activation. Herein we discuss both direct and indirect strategies aimed at targeting B cells in patients with lupus by blocking BAFF, type I interferon, or TLR7 to TLR9. Although BAFF-depleting therapy with belimumab achieved approval for lupus, other BAFF inhibitors were much less beneficial in clinical trials. Inhibitors of the B-cell receptor for antigen signaling and antibodies against type I interferon are in the pipeline. The TLR7 to TLR9 blocker hydroxychloroquine has been in use in patients with lupus for more than 50 years, but oligonucleotide-based inhibitors of TLR7 to TLR9, despite showing promise in animal models of lupus, have not reached the primary end point in a recent phase 1 trial. These data point toward possible redundancies in B-cell signaling/survival pathways, which must be better understood before future clinical trials are executed.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Allergy and Clinical Immunology - Volume 137, Issue 5, May 2016, Pages 1325-1333
Journal: Journal of Allergy and Clinical Immunology - Volume 137, Issue 5, May 2016, Pages 1325-1333
نویسندگان
Namrata MD, Bharat MD, Vijay MD, Petar MD, PhD,