Interfering with baffled B cells at the lupus tollway: Promises, successes, and failed expectations

Namrata Singh; Bharat Kumar; Vijay Aluri; Petar Lenert

doi:10.1016/j.jaci.2015.12.1326

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Interfering with baffled B cells at the lupus tollway: Promises, successes, and failed expectations

Journal article

Open access

Peer reviewed

Interfering with baffled B cells at the lupus tollway: Promises, successes, and failed expectations

Namrata Singh, Bharat Kumar, Vijay Aluri and Petar Lenert

Journal of allergy and clinical immunology, Vol.137(5), pp.1325-1333

05/2016

DOI: 10.1016/j.jaci.2015.12.1326

PMID: 26953155

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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.

Tumor Necrosis Factor Ligand Superfamily Member 13 - immunology

Animals

B-Lymphocytes - immunology

Humans

Toll-Like Receptors - immunology

Lupus Erythematosus, Systemic - immunology

Toll-Like Receptors - antagonists & inhibitors

B-Cell Activating Factor - immunology

Syk Kinase - antagonists & inhibitors

Interferon Type I - immunology

Protein-Tyrosine Kinases - antagonists & inhibitors

Details

Title: Subtitle: Interfering with baffled B cells at the lupus tollway: Promises, successes, and failed expectations
Creators: Namrata Singh - Division of Immunology, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa
Bharat Kumar - Division of Immunology, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa
Vijay Aluri - Division of Immunology, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa
Petar Lenert - Division of Immunology, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa. Electronic address: petar-lenert@uiowa.edu
Resource Type: Journal article
Publication Details: Journal of allergy and clinical immunology, Vol.137(5), pp.1325-1333
DOI: 10.1016/j.jaci.2015.12.1326
PMID: 26953155
ISSN: 0091-6749
eISSN: 1097-6825
Language: English
Date published: 05/2016
Academic Unit: Epidemiology; Immunology; Internal Medicine
Record Identifier: 9984094399102771

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