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
DOI
10.1126/scitranslmed.aaa3809