BAFF and innate immunity: new therapeutic targets for systemic lupus erythematosus

  title={BAFF and innate immunity: new therapeutic targets for systemic lupus erythematosus},
  author={Fabien B Vincent and Eric F. Morand and Fabienne Mackay},
  journal={Immunology and Cell Biology},
Recently, the B cell has emerged as a cornerstone of systemic lupus erythematosus (SLE) pathogenesis. This has been highlighted by studies of the cytokine B‐cell‐activating factor of the tumour necrosis factor (TNF) family (BAFF), a crucial factor regulating B‐cell maturation, survival and function. Overexpression of BAFF in mice leads to the development of an SLE‐like disease, independent of T cells but instead relying on innate immunity mechanisms. Moreover, BAFF has been shown to be elevated… 

The BAFF/APRIL system in SLE pathogenesis

Results suggesting that neutralizing BAFF can have effects on the immune system other than depletion of B cells are reviewed, and aspects of the BAFF system for which data in relation to SLE are still missing are identified.

The BAFF / APRIL system as therapeutic target in multiple sclerosis

A more comprehensive understanding of the cell/molecular mechanism immune reactions specifically regulated by BAFF/APRIL in MS would better elucidate the specific cell phenotype targeted by actual anti-BAFF/apRIL therapies; this may enable the identification of either specific biomarkers of MS subgroups that would benefit of anti- BAFF or APRIL treatments or new targets of MS-specific anti-APRil therapies.

Immune Profiling of Systemic Lupus Erythematosus

Models for predicting if an individual has SLE, if an SLE patient has renal involvement and predicting SLE Disease Activity Index are developed, forming the basis for improved diagnosis and assessment of SLE in the future.

The BAFF/APRIL system: Emerging functions beyond B cell biology and autoimmunity

Targeting B Cells and Plasma Cells in Glomerular Diseases: Translational Perspectives.

Whereas memory B cells and plasma cells appear to be key in ANCA-associated vasculitis and antibody-mediated transplant rejection, respectively, SLE seems likely to be driven by both autoimmune compartments, which have implications for the future development of targeted therapeutics in immune-mediated renal disease.

B-cell-targeted therapies in systemic lupus erythematosus and ANCA-associated vasculitis: current progress

In anti-neutrophil cytoplasmic antibody-associated vasculitis, rituximab is effective for remission induction and in relapsing disease, however, the optimal long-term re-treatment strategy remains to be determined.

Renal tubular epithelial cell-derived BAFF expression mediates kidney damage and correlates with activity of proliferative lupus nephritis in mouse and men

Investigating whether renal tubular epithelial cells (TEC) are an important source of BAFF and thus may contribute to the pathogenesis and progression of SLE indicates that renal-derived BAFF may play an important role in the pathophysiology of the systemic autoimmune disease SLE.

Novel contributors to B cell activation during inflammatory CNS demyelination; An oNGOing process

Current evidence for BAFF-dependent signaling through the NgR multimeric complex is provided, elucidating their association within the CNS compartment and underlying the importance of these potential pathogenic molecular regulators as possible therapeutic targets to limit relapse rates and potentially MS progression.

Role of B-Cell Activating Factor (BAFF) in Inflammatory Bowel Disease

The current evidence with respect to the role of BAFF in diagnosis and assessing the activity of IBD is summarized, as well as putative therapeutic implications that may arise from exploring of this relation.

Systemic Lupus Erythematosus (SLE) Therapy: The Old and the New

Current pharmacological and non-pharmacological treatment options and emerging therapies in SLE are provided and growing evidence is emerging of the importance of correct lifestyle habits in the management of lupus manifestations and comorbidities.



BAFF and MyD88 signals promote a lupuslike disease independent of T cells

Autoimmunity in BAFF Tg mice results from altered B cell tolerance, but requires TLR signaling and is independent of T cell help, and it is possible that SLE patients with elevated levels of BAFF show a similar basis for disease.

Insights into the heterogeneity of human B cells: diverse functions, roles in autoimmunity, and use as therapeutic targets

A better understanding of B cell functions is of the essence and a focus of the research in this division, which is investigating these issues through a variety of approaches, including the study of the phenotype and function of human B cell populations in health, their perturbation in autoimmune disease states, the effects of targeted biologic therapies, and theStudy of relevant murine models.

Cutting Edge: A Role for B Lymphocyte Stimulator in Systemic Lupus Erythematosus1

The results suggest that BLyS may be a useful marker for early activation of an autoimmune diathesis and likely plays a critical role in triggering activation of self-Ag-driven autoimmune B cells in human SLE and may provide an effective therapeutic target in systemic autoimmunity.

TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease

These findings demonstrate the involvement of zTNF4 and its receptors in the development of SLE and identify TACI–Ig as a promising treatment of autoimmune disease in humans.

Depletion of B Cells in Murine Lupus: Efficacy and Resistance1

Whereas successful B cell depletion is a promising therapy for lupus, at least some patients might be resistant to the therapy as a byproduct of the autoimmune condition itself, and this was true with multiple anti-CD20 Abs, including a new anti-mouse CD20 Ab, and in several different autoimmune-prone strains.

The innate immune system in SLE: type I interferons and dendritic cells

A new therapeutic option in patients with SLE is inhibition of IFN- α, and recent data from a phase I clinical trial suggests that administration of neutralizing monoclonal antibodies against anti-IFN-α can ameliorate disease activity.

Differential effects on BAFF and APRIL levels in rituximab-treated patients with systemic lupus erythematosus and rheumatoid arthritis

Increased BAFF levels were observed during absence of circulating B cells in patients with systemic lupus erythematosus and rheumatoid arthritis treated with the B-cell-depleting agent rituximab, suggesting that BAFF and APRIL are differentially regulated in different autoimmune diseases and, in addition, differently affected by ritUXimab treatment.

Importance of Cellular Microenvironment and Circulatory Dynamics in B Cell Immunotherapy1

It is demonstrated that factors derived from the microenvironment, including signals from the B cell-activating factor belonging to the TNF family/BLyS survival factor, integrin-regulated homeostasis, and circulatory dynamics of B cells define distinct in vivo mechanism(s) and sensitivities of cells in anti-hCD20 mAb-directed therapies.

BAFF Augments Certain Th1-Associated Inflammatory Responses1

Using BAFF Tg mice, a typical Th1-mediated response, the cutaneous delayed-type hypersensitivity reaction, is examined, and a much greater degree of paw swelling and inflammation is found than in control mice, consistent with the idea that BAFF augments T cell as well as B cell responses, particularly Th2-type responses.