Improving B-cell depletion in systemic lupus erythematosus and rheumatoid arthritis

Mota, Pedro; Reddy, Venkat; Isenberg, David

doi:10.1080/1744666x.2017.1259068

Cited by 15 publications

(13 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The establishment of RTX B-cell depletion therapy in SLE by clinical trials has confronted several hurdles including the heterogeneity of the disease and the beneficial effects of background therapy that might mask the added value of short-term RTX treatment (61). Small study size, lack of robust design, and shortterm follow-up are further limitations of RTX clinical trials.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Outcomes of rituximab therapy in refractory lupus: A meta-analysis

Alshaiki¹,

Obaid²,

Almuallim³

et al. 2018

Eur J Rheumatol

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

“…B lymphocytes are documented to play a major role in the pathogenesis of SLE (61). Thus, B-cell depletion therapy has gained much interest for management of SLE and LN.…”

Section: Discussionmentioning

confidence: 99%

Outcomes of rituximab therapy in refractory lupus: A meta-analysis

Alshaiki¹,

Obaid²,

Almuallim³

et al. 2018

Eur J Rheumatol

View full text Add to dashboard Cite

“…Nevertheless, the targeting of B cell survival through B cell activating factor (BAFF) inhibition has shown some success for the treatment of less severe disease manifestations, such as skin and joint manifestations in certain trials (123,124). The failure of rituximab and certain BAFF inhibitors in some SLE trials is in contrast to clinical experience and treatment guidelines (125). Numerous reasons for these failed trials have been proposed, including the liberal additional use of glucocorticoids to treat patients (potentially masking a beneficial impact of rituximab) and the inability of rituximab to successfully deplete tissue memory B cells (125).…”

Section: [H2] Kidney Transplantationmentioning

confidence: 99%

“…The failure of rituximab and certain BAFF inhibitors in some SLE trials is in contrast to clinical experience and treatment guidelines (125). Numerous reasons for these failed trials have been proposed, including the liberal additional use of glucocorticoids to treat patients (potentially masking a beneficial impact of rituximab) and the inability of rituximab to successfully deplete tissue memory B cells (125).…”

Section: [H2] Kidney Transplantationmentioning

confidence: 99%

Effector and regulatory B cells in immune-mediated kidney disease

2018

View full text Add to dashboard Cite

B cells have a central role in many autoimmune diseases, including in those with renal involvement, as well as in the immunological response to kidney transplantation. The majority of studies of B cells have focused on their pathological role as antibody producers. However, these cells have broad functions in immune responses beyond immunoglobulin secretion, including antigen presentation to T cells and cytokine production. Importantly, not all B cell subsets enhance immune responses. Regulatory B (Breg) cells attenuate inflammation and contribute to the maintenance of immune tolerance. Breg cells are numerically deficient and/or dysfunctional in several autoimmune diseases that can affect the kidney, including systemic lupus erythematosus and anti-neutrophil cytoplasmic antibody-associated vasculitis, as well as in some groups of renal transplant recipients with alloimmune graft damage. B cell-targeting biologics have been trialled with promising results in diverse immune-mediated renal conditions. These therapies can affect both pro-inflammatory B cells and Breg cells potentially limiting their long-term efficacy. Future strategies might involve the modulation of inflammatory B cells in combination with the stimulation of regulatory subsets. Additionally, the monitoring of individual B cell subsets in patients may lead to the discovery of novel biomarkers that could help to predict disease relapse or progression.

show abstract

“…Ectopic lymphoid foci often develop, behaving as sources of ABLs and ASCs that migrate and accumulate in damaged organs and tissues where they receive signals for survival and maturation [8][9][10][11][12][13]. Therefore, B lymphocytes and ASCs are considered relevant targets for therapy in SLE and RA patients [14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Autoreactive B‐lymphocytes in SLE and RA patients: Isolation and characterisation using extractable nuclear and citrullinated antigens bound to immunobeads

et al. 2019

View full text Add to dashboard Cite

Systemic lupus erythematosus and rheumatoid arthritis are autoimmune diseases characterised by B-cell hyperactivation and production of autoantibodies (AutoAbs) against various self-antigens, including extractable nuclear antigens and citrullinated peptides. Therefore, B lymphocytes and antibody-secreting cells are considered relevant targets for therapies. However, isolation and characterisation of auto-reactive specific B lymphocytes are limited, primarily due to technical issues. In this work, we purified extractable nuclear antigen-specific and citrullinated peptide-specific auto-reactive B lymphocytes by magnetic selection with ENA-and citrullinated peptide-bound immunobeads. We obtained blood auto-reactive B lymphocytes from most patients. Their nature was primarily naïve B cells, some of them in an active status, with low levels of somatic hypermutations in the immunoglobulin heavy-chain variable regions. Their presence correlated with serum levels of autoAb. Auto-reactive B lymphocytes were able to differentiate into auto-reactive antibody-secreting cells under conditions of stimulation. In addition, based on the presence of circulating auto-reactive B cells and/or antibody-secreting cells, four different profiles were described in lupus patients. Thus, tracking auto-reactive B cells and/or antibody-secreting cells in patient blood could represent a biomarker for deciding whether to use therapies blocking either B cells, plasma cells or both, as well as a new tool for monitoring minimal residual autoimmune disease in patients.Keywords: B cells r citrullinated peptide r rheumatoid arthritis r systemic lupus erythematosus Additional supporting information may be found online in the Supporting Information section at the end of the article.

show abstract

Improving B-cell depletion in systemic lupus erythematosus and rheumatoid arthritis

Cited by 15 publications

References 81 publications

Outcomes of rituximab therapy in refractory lupus: A meta-analysis

Outcomes of rituximab therapy in refractory lupus: A meta-analysis

Effector and regulatory B cells in immune-mediated kidney disease

Autoreactive B‐lymphocytes in SLE and RA patients: Isolation and characterisation using extractable nuclear and citrullinated antigens bound to immunobeads

Contact Info

Product

Resources

About