BAFF inhibition in SLE—Is tolerance restored?

Jackson, Shaun W.; Davidson, Anne

doi:10.1111/imr.12810

Cited by 51 publications

(40 citation statements)

References 148 publications

(274 reference statements)

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“…Inhibition of the cytokine B cell-activating factor (BAFF) can facilitate B cell tolerance (reviewed in ref. 46). Consistent with the lack of B cell deletion in this CoB/DSC model of tolerance, the levels of circulating BAFF were not reduced in tolerant recipients compared with naive mice, or in MD4 hosts receiving tolerant or naive B cells (Supplemental Figure 8).…”

Section: Discussionsupporting

confidence: 70%

Transplantation tolerance modifies donor-specific B cell fate to suppress de novo alloreactive B cells

Khiew

Jain

Chen

et al. 2020

Journal of Clinical Investigation

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Section: Discussionsupporting

confidence: 70%

Transplantation tolerance modifies donor-specific B cell fate to suppress de novo alloreactive B cells

Khiew

Jain

Chen

et al. 2020

Journal of Clinical Investigation

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“…NETs are a known source of autoantigens, and cytokines released in parallel with NETosis may also facilitate NET-associated autoantibody propagation (77)(78)(79)(80). An example of a cytokine that could play such a role is B cell activating factor (BAFF), an important mediator of the maturation of B cells into antibody-producing cells (81). For example, neutrophil-derived BAFF likely participates in the production of anti-double-stranded DNA antibodies in lupus (78).…”

Section: Discussionmentioning

confidence: 99%

Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19

et al. 2020

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Patients with COVID-19 are at high risk for thrombotic arterial and venous occlusions. Lung histopathology often reveals fibrin-based blockages in the small blood vessels of patients who succumb to the disease. Antiphospholipid syndrome is an acquired and potentially life-threatening thrombophilia in which patients develop pathogenic autoantibodies targeting phospholipids and phospholipid-binding proteins (aPL antibodies). Case series have recently detected aPL antibodies in patients with COVID-19. Here, we measured eight types of aPL antibodies in serum samples from 172 patients hospitalized with COVID-19. These aPL antibodies included anticardiolipin IgG, IgM, and IgA; anti–β2 glycoprotein I IgG, IgM, and IgA; and anti-phosphatidylserine/prothrombin (aPS/PT) IgG and IgM. We detected aPS/PT IgG in 24% of serum samples, anticardiolipin IgM in 23% of samples, and aPS/PT IgM in 18% of samples. Antiphospholipid autoantibodies were present in 52% of serum samples using the manufacturer’s threshold and in 30% using a more stringent cutoff (≥40 ELISA-specific units). Higher titers of aPL antibodies were associated with neutrophil hyperactivity, including the release of neutrophil extracellular traps (NETs), higher platelet counts, more severe respiratory disease, and lower clinical estimated glomerular filtration rate. Similar to IgG from patients with antiphospholipid syndrome, IgG fractions isolated from patients with COVID-19 promoted NET release from neutrophils isolated from healthy individuals. Furthermore, injection of IgG purified from COVID-19 patient serum into mice accelerated venous thrombosis in two mouse models. These findings suggest that half of patients hospitalized with COVID-19 become at least transiently positive for aPL antibodies and that these autoantibodies are potentially pathogenic.

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“…BAFF antagonists have been successfully introduced in the treatment of NMOSD-related diseases like systemic lupus erythematosus [ 201 ]. To our knowledge, there are no reports about BAFF antagonism in NMOSD, which might be an auspicious option.…”

Section: Ineffectiveness and Failure Of Ms Therapeutics In Nmosdmentioning

confidence: 99%

Differential Effects of MS Therapeutics on B Cells—Implications for Their Use and Failure in AQP4-Positive NMOSD Patients

Traub

Häusser‐Kinzel

Weber

2020

IJMS

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B cells are considered major contributors to multiple sclerosis (MS) pathophysiology. While lately approved disease-modifying drugs like ocrelizumab deplete B cells directly, most MS medications were not primarily designed to target B cells. Here, we review the current understanding how approved MS medications affect peripheral B lymphocytes in humans. These highly contrasting effects are of substantial importance when considering these drugs as therapy for neuromyelitis optica spectrum disorders (NMOSD), a frequent differential diagnosis to MS, which is considered being a primarily B cell- and antibody-driven diseases. Data indicates that MS medications, which deplete B cells or induce an anti-inflammatory phenotype of the remaining ones, were effective and safe in aquaporin-4 antibody positive NMOSD. In contrast, drugs such as natalizumab and interferon-β, which lead to activation and accumulation of B cells in the peripheral blood, lack efficacy or even induce catastrophic disease activity in NMOSD. Hence, we conclude that the differential effect of MS drugs on B cells is one potential parameter determining the therapeutic efficacy or failure in antibody-dependent diseases like seropositive NMOSD.

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BAFF inhibition in SLE—Is tolerance restored?

Cited by 51 publications

References 148 publications

Transplantation tolerance modifies donor-specific B cell fate to suppress de novo alloreactive B cells

Transplantation tolerance modifies donor-specific B cell fate to suppress de novo alloreactive B cells

Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19

Differential Effects of MS Therapeutics on B Cells—Implications for Their Use and Failure in AQP4-Positive NMOSD Patients

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