Differences in Dynamics of Specific Antinuclear Antibodies and Their Susceptibility to B Cell-Targeting Treatment in Patients With Systemic Lupus Erythematosus.

Objective: The presence of antinuclear antibodies (ANAs) is characteristic for systemic lupus erythematosus (SLE). Antibody dynamics over time are thought to reflect the cellular source of ANAs and their therapeutic targetability. Anti-double-stranded DNA (anti-dsDNA) is the most prevalent and well-studied of all ANAs, and fluctuations in anti-dsDNA serum levels are associated with disease activity.

Long-term safety and efficacy of the combination of belimumab and rituximab in the treatment of severe and refractory SLE: a preliminary report.

Objective: Combination therapy with rituximab and belimumab is a novel treatment strategy for severe SLE and lupus nephritis. Phase II studies have shown promising results, although long-term data are currently lacking. To address this, we analysed outcomes of patients with severe treatment-refractory SLE who previously participated in the phase II Synbiose Study, with a particular focus on immunological parameters.

Disruption of memory B-cell trafficking by belimumab in patients with systemic lupus erythematosus.

Objectives: Autoreactive memory B cells (MBCs) contribute to chronic and progressive courses in autoimmune diseases like SLE. The efficacy of belimumab (BEL), the first approved biologic treatment for SLE and LN, is generally attributed to depletion of activated naïve B cells and inhibition of B-cell activation. BEL's effect on MBCs is currently unexplained.

Voclosporin and the Antiviral Effect Against SARS-CoV-2 in Immunocompromised Kidney Patients.

Introduction: Immunocompromised kidney patients are at increased risk of prolonged SARS-CoV-2 infection and related complications. Preclinical evidence demonstrates a more potent inhibitory effect of voclosporin on SARS-CoV-2 replication than tacrolimus . We investigated the potential antiviral effects of voclosporin on SARS-CoV-2 in immunocompromised patients.

Efficacy of belimumab combined with rituximab in severe systemic lupus erythematosus: study protocol for the phase 3, multicenter, randomized, open-label Synbiose 2 trial.

Background: Belimumab, an anti-B-cell activating factor antibody, is approved for the treatment of auto-antibody positive systemic lupus erythematosus with a high degree of disease activity. Anti-CD20 B cell depletion with rituximab is used in refractory SLE as well, although with variable responses. We hypothesized that incomplete B cell depletion, related to a surge in BAFF levels following rituximab treatment, can cause ongoing disease activity and flares.

The Cyclophilin-Dependent Calcineurin Inhibitor Voclosporin Inhibits SARS-CoV-2 Replication in Cell Culture.

Kidney transplant recipients (KTRs) are at increased risk for a more severe course of COVID-19, due to their pre-existing comorbidity and immunosuppression. Consensus protocols recommend lowering immunosuppression in KTRs with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but the optimal combination remains unclear. Calcineurin inhibitors (CNIs) are cornerstone immunosuppressants used in KTRs and some have been reported to possess antiviral activity against RNA viruses, including coronaviruses.

Increased Tacrolimus Exposure in Kidney Transplant Recipients With COVID-19: Inflammation-Driven Downregulation of Metabolism as a Potential Mechanism.

Kidney transplant recipients (KTRs) are at increased risk of severe COVID-19 disease compared to the general population. This is partly driven by their use of immunosuppressive therapy, which influences inflammatory responses and viral loads. Current guidelines suggest to withdraw mycophenolate while calcineurin inhibitors are often continued during a COVID-19 infection.

Highly Sensitive Flow Cytometric Detection of Residual B-Cells After Rituximab in Anti-Neutrophil Cytoplasmic Antibodies-Associated Vasculitis Patients.

Background: B-cell depletion with rituximab (RTX) is an effective treatment for anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients. Nevertheless, relapses are frequent after RTX, often preceded by B-cell repopulation suggesting that residual autoreactive B-cells persist despite therapy. Therefore, this study aimed to identify minimal residual autoimmunity (MRA) in the B-cell compartment of AAV patients treated with RTX.

Long-term effects of combined B-cell immunomodulation with rituximab and belimumab in severe, refractory systemic lupus erythematosus: 2-year results.

Background: Anti-CD20 B-cell depletion has not shown superior efficacy to standard immunosuppression in patients with systemic lupus erythematosus (SLE). Besides trial design, potential explanations are incomplete B-cell depletion in relation to substantial surges in B-cell-activating factor (BAFF). To improve B-cell targeting strategies, we conducted the first study in SLE patients aimed at investigating immunological effects and feasibility of combining rituximab (RTX; anti-CD20) and belimumab (BLM; anti-BAFF).

A High-throughput Assay to Assess and Quantify Neutrophil Extracellular Trap Formation.

Neutrophil extracellular traps (NETs) are immunogenic extracellular DNA structures that can be released by neutrophils upon a wide variety of triggers. NETs have been demonstrated to serve as an important host defense mechanism that traps and kills microorganisms. On the other hand, they have been implicated in diverse systemic autoimmune diseases.