Title

Therapeutics to block autoantibody initiation and propagation in systemic lupus erythematosus and rheumatoid arthritis

Publication Date

2015

Journal Title

Sci Transl Med

Abstract

Most current therapies for the autoimmune diseases systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), as well as many of the drugs in the therapeutic pipeline, reduce the autoimmune inflammatory process but lead to a general immunosuppression. The goal of the next generation of therapies should be to reduce autoimmunity while at the same time better maintain immunocompetence. We propose three approaches for accomplishing this goal: (i) modulate antigen presentation to the adaptive immune system, (ii) alter B cell selection in the germinal center, and (iii) use decoy antigens to prevent the formation of proinflammatory immune complexes. These approaches are based on recent advances in the field: We now appreciate the role of dendritic cell function in autoimmune disease and the importance of citrullinated proteins as neoantigens in RA. There is also new recognition that most pathogenic autoantibodies are produced by B cells that have matured within the germinal center and that immune complexes in both diseases contain ligands for Toll-like receptors. We propose that treatments that target these newly revealed aspects of RA and SLE will decrease systemic inflammation with less immunocompromise.

Volume Number

7

Issue Number

280

Pages

5

Document Type

Article

EPub Date

2015/03/27

Status

Faculty; Northwell Researcher

Facility

School of Medicine; Northwell Health

Primary Department

Molecular Medicine

Additional Departments

General Internal Medicine

PMID

25810309

DOI

10.1126/scitranslmed.aaa3809

For the public and Northwell Health campuses

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