Does rituximab improve clinical outcomes of patients with thyroid-associated ophthalmopathy? A systematic review and meta-analysis

Wang, Changjun; Ning, Qingyao; Jin, Kai; Xie, Jiajun

doi:10.1186/s12886-018-0679-4

Cited by 23 publications

(9 citation statements)

References 30 publications

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“…Next, B cells returning after depletion secreted reduced levels of interleukin-6 in humans [ 113 ]. However, interleukin-6 serum levels were shown to be unaffected six months after B cell depletion [ 114 ].…”

Section: Effects Of Ms Medications On Peripheral B Cells In Humansmentioning

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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Section: Effects Of Ms Medications On Peripheral B Cells In Humansmentioning

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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“…However, our studies showed some positive association of aequorin TSAb and the effect of pulse therapy on different orbital findings. We, therefore, emphasized the clinical usefulness of this new assay and the importance of prospective monitoring during conventional treatment or new pharmacological treatments for GO [19,20]. Further prospective studies are indicated to clarify the use-fulness of this assay to assess the occurrence or progression of ophthalmopathy.…”

Section: Discussionmentioning

confidence: 98%

Role of a new bioassay for thyroid-stimulating antibodies (aequorin TSAb) in Graves’ ophthalmopathy

et al. 2020

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Graves' ophthalmopathy (GO) is characterized by an autoimmune reaction against thyrotropin (TSH) receptors and is diagnosed by TSH receptor antibody (TRAb). A novel assay for thyroid-stimulating antibody (TSAb) was recently introduced using a frozen Chinese hamster ovary cell line expressing TSH receptors, cyclic adenosine monophosphate (cAMP)-gated calcium channel, and aequorin (aequorin TSAb). The aim of this study was to evaluate the role of aequorin TSAb in GO. We studied 136 Japanese patients with GO (22 euthyroid and 8 hypothyroid GO patients) at our hospital. TRAbs were estimated by first generation TRAb (TRAb 1 st), second generation TRAb (hTRAb 2 nd), conventional porcine TSAb, and the new aequorin TSAb assays. Aequorin TSAb, porcine TSAb, TRAb 1 st , and hTRAb 2 nd were positive in 125/136 (92%), 110/136 (81%), 81/130 (62%), and 93/114 (82%) patients, respectively. In patients with hyperthyroid GO, they were positive in 98/106 (98%), 96/106 (91%), 78/101 (77%), and 84/93 (90%) patients, respectively. In patients with euthyroid GO, they were positive in 19/22 (86%), 9/22 (41%), 1/21 (5%), and 6/17 (35%) patients, respectively. Aequorin TSAb levels were significantly related to TRAb 1 st (r = 0.4172, p < 0.0001), hTRAb 2 nd (r = 0.2592, p < 0.0001), and porcine TSAb (r = 0.4665, p < 0.0001). Clinical activity score (CAS) was significantly greater in patients with high titers of aequorin TSAb than in those with low titers. Aequorin TSAb levels were significantly related to the signal intensity ratio of the enlarged eye muscle and proptosis evaluated by MRI before steroid pulse therapy. Aequorin TSAb assay was more sensitive than the conventional assays, especially in euthyroid GO.

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“…In SLE and rheumatoid arthritis patients, BAFF levels were found to be elevated during B-cell depletion and declined upon B-cell repopulation [ 131 , 132 ]. B cells returning after depletion secreted reduced levels of IL-6 in humans and IL-6 serum levels were shown to be unaffected six months after B cell depletion [ 22 , 133 ]. Further, the depletion of regulatory B cells was associated with an enhanced secretion of pro-inflammatory cytokines by CD11b + antigen-presenting cells [ 134 ].…”

Section: Current and Evolving Therapeutic Strategies In Nmosdmentioning

confidence: 99%

B Cells and Antibodies as Targets of Therapeutic Intervention in Neuromyelitis Optica Spectrum Disorders

Traub¹,

Husseini

Weber

2021

Pharmaceuticals

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The first description of neuromyelitis optica by Eugène Devic and Fernand Gault dates back to the 19th century, but only the discovery of aquaporin-4 autoantibodies in a major subset of affected patients in 2004 led to a fundamentally revised disease concept: Neuromyelits optica spectrum disorders (NMOSD) are now considered autoantibody-mediated autoimmune diseases, bringing the pivotal pathogenetic role of B cells and plasma cells into focus. Not long ago, there was no approved medication for this deleterious disease and off-label therapies were the only treatment options for affected patients. Within the last years, there has been a tremendous development of novel therapies with diverse treatment strategies: immunosuppression, B cell depletion, complement factor antagonism and interleukin-6 receptor blockage were shown to be effective and promising therapeutic interventions. This has led to the long-expected official approval of eculizumab in 2019 and inebilizumab in 2020. In this article, we review current pathogenetic concepts in NMOSD with a focus on the role of B cells and autoantibodies as major contributors to the propagation of these diseases. Lastly, by highlighting promising experimental and future treatment options, we aim to round up the current state of knowledge on the therapeutic arsenal in NMOSD.

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Does rituximab improve clinical outcomes of patients with thyroid-associated ophthalmopathy? A systematic review and meta-analysis

Cited by 23 publications

References 30 publications

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

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

Role of a new bioassay for thyroid-stimulating antibodies (aequorin TSAb) in Graves’ ophthalmopathy

B Cells and Antibodies as Targets of Therapeutic Intervention in Neuromyelitis Optica Spectrum Disorders

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