Interfering with baffled B cells at the lupus tollway: Promises, successes, and failed expectations.
J Allergy Clin Immunol
; 137(5): 1325-33, 2016 05.
Article
in En
| MEDLINE
| ID: mdl-26953155
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
B-Lymphocytes
/
Lupus Erythematosus, Systemic
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
J Allergy Clin Immunol
Year:
2016
Document type:
Article