The clinical value of hematological markers in rheumatoid arthritis patients treated with tocilizumab

Zhou, Li; Xiao, Dongmei; Qin, Wen; Xie, Binhua; Wang, Ting‐Hui; Hua, Huang; Zhao, Bao‐Jing; Han, Xi; Sun, Qingqing; Wu, Xiudi; Cen, Han

doi:10.1002/jcla.22862

Cited by 10 publications

(9 citation statements)

References 43 publications

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“…In addition, PBMC hsa_circ_0000175 was correlated with inflammatory markers, including WBc, N, N%, L, L% and NLR, which reflect the activity and severity of RA (28). Moreover, PBMC hsa_circ_0008410 was correlated with TJc, disease duration and PLT, which are associated with the development of peripheral neuropathy and are correlated with dAS28 (29,30), and PcT, which is associated with the treatment of RA (31). Thus, these data indicated that PBMc hsa_circ_0000175 and hsa_ circ_0008410 were associated with the activity and severity of RA.…”

Section: Discussionmentioning

confidence: 98%

Expression and clinical significance of circular RNAs hsa_circ_0000175 and hsa_circ_0008410 in peripheral blood mononuclear cells from patients with rheumatoid arthritis

Luo

Zeng

et al. 2020

Int J Mol Med

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circular RNAs (circRNAs) are a novel class of RNAs that may be used as biomarkers in clinical blood samples. However, the role of circRNAs in rheumatoid arthritis (RA) has not been extensively investigated. In the present study, six circRNAs, including hsa_circ_0082689, hsa_circ_0087798, hsa_circ_0000175, hsa_circ_0008410, hsa_circ_0049356 and hsa_circ_0032959 levels were determined in peripheral blood mononuclear cells (PBMcs) collected from 24 patients with RA and 24 healthy controls (Hc) by reverse transcription-quantitative polymerase chain reaction (RT-qPcR) analysis. Hsa_circ_0000175 and hsa_circ_0008410 were selected for further evaluation in an independent cohort consisting of 63 patients with RA, 50 with systemic lupus erythematosus (SLE), 24 with ankylosing spondylitis (AS) and 21 Hc. Spearman's rank correlation coefficient was used to analyze the correlation between these two circRNAs and the clinical characteristics of RA, and receiver operating characteristic (ROc) curves were constructed to evaluate their value in RA diagnosis. Multivariate analysis (logistic regression) was used to analyze the risk factors. Of the six selected circRNAs, the expression of hsa_circ_0000175 was found to be significantly reduced and the expression of hsa_circ_0008410 was significantly elevated in PBMCs from patients with RA compared with their levels in Hc. The expression of hsa_circ_0000175 in patients with RA was correlated with anti-citrullinated protein antibodies, white blood cell count, lymphocyte count, lymphocyte percentage, neutrophil count, neutrophil percentage and neutrophil-to-lymphocyte ratio. Furthermore, the expression of hsa_circ_0008410 was correlated with tender joint count, disease duration, platelet count and plateletcrit, indicating the activity and severity of RA. ROc curve analysis suggested that hsa_circ_0000175, hsa_circ_0008410, and the combination of hsa_circ_0000175 and hsa_circ_0008410 have significant value in the diagnosis of RA. Hsa_circ_0000175 and hsa_circ_0008410 also differed significantly between patients with RA, and those with SLE and AS. Moreover, logistic regression analysis revealed that the expression of PBMc hsa_circ_0000175 and hsa_circ_0008410 were risk factors for RA. Therefore, PBMc hsa_circ_0000175, hsa_circ_0008410, and the combination of PBMc hsa_circ_0000175 and hsa_circ_0008410 may improve the diagnostic accuracy for RA. In addition, the expression levels of PBMc hsa_circ_0000175 and hsa_circ_0008410 were associated with disease activity and severity of RA.

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Section: Discussionmentioning

confidence: 98%

Expression and clinical significance of circular RNAs hsa_circ_0000175 and hsa_circ_0008410 in peripheral blood mononuclear cells from patients with rheumatoid arthritis

Luo

Zeng

et al. 2020

Int J Mol Med

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“…In a more recent trial with 118 included patients, 92% of treated NMOSD patients were relapse-free after 48 weeks compared to 69% in the azathioprine group with similar findings regarding disability progression [ 233 ]. Neither did treatment alter lymphocyte, B cell, transitional B cell and plasmablast count, nor did it alter BAFF levels of treated patients [ 234 , 235 ]. However, Toclizumab was shown to reduce memory B cell subsets in rheumatoid arthritis patients as well as IgA and IgG serum levels [ 236 ].…”

Section: Novel and Future Nmosd Treatmentsmentioning

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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“…Treatment with tocilizumab had neither an impact on total lymphocyte count and absolute B cell, transitional B cell and plasmablast numbers, nor did it alter BAFF levels of treated patients [ 156 , 157 ]. However, tocilizumab was shown to reduce memory B cell subsets as well as IgA and IgG serum levels in rheumatoid arthritis patients [ 158 ].…”

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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The clinical value of hematological markers in rheumatoid arthritis patients treated with tocilizumab

Cited by 10 publications

References 43 publications

Expression and clinical significance of circular RNAs hsa_circ_0000175 and hsa_circ_0008410 in peripheral blood mononuclear cells from patients with rheumatoid arthritis

Expression and clinical significance of circular RNAs hsa_circ_0000175 and hsa_circ_0008410 in peripheral blood mononuclear cells from patients with rheumatoid arthritis

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

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

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