Targeting BAFF and APRIL in systemic lupus erythematosus and other antibody-associated diseases.
Int Rev Immunol
; 36(1): 3-19, 2017 01 02.
Article
en En
| MEDLINE
| ID: mdl-28215100
ABSTRACT
The B cell-stimulating molecules, BAFF (B cell activating factor) and APRIL (a proliferation-inducing ligand), are critical factors in the maintenance of the B cell pool and humoral immunity. In addition, BAFF and APRIL are involved in the pathogenesis of a number of human autoimmune diseases, with elevated levels of these cytokines detected in the sera of patients with systemic lupus erythematosus (SLE), IgA nephropathy, Sjögren's syndrome, and rheumatoid arthritis. As such, both molecules are rational targets for new therapies in B cell-driven autoimmune diseases, and several inhibitors of BAFF or BAFF and APRIL together have been investigated in clinical trials. These include the BAFF/APRIL dual inhibitor, atacicept, and the BAFF inhibitor, belimumab, which is approved as an add-on therapy for patients with active SLE. Post hoc analyses of these trials indicate that baseline serum levels of BAFF and BAFF/APRIL correlate with treatment response to belimumab and atacicept, respectively, suggesting a role for the two molecules as predictive biomarkers. It will, however, be important to refine future testing to identify active forms of BAFF and APRIL in the circulation, as well as to distinguish between homotrimer and heteromer configurations. In this review, we discuss the rationale for dual BAFF/APRIL inhibition versus single BAFF inhibition in autoimmune disease, by focusing on the similarities and differences between the physiological and pathogenic roles of the two molecules. A summary of the preclinical and clinical data currently available is also presented.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Linfocitos B
/
Factor Activador de Células B
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Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral
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Inmunoterapia
/
Lupus Eritematoso Sistémico
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Int Rev Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos