Targeted B cell therapies in the treatment of adult and pediatric systemic lupus erythematosus

Hui-Yuen, Joyce; Nguyen, Samantha; Askanase, Anca

doi:10.1177/0961203316652491

Cited by 23 publications

(14 citation statements)

References 64 publications

(112 reference statements)

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“…Of interest, systemic lupus erythematosus (SLE) ranked first. SLE is due to the inability of individual’s immune system to distinguish between self and non-self-antigens, resulting in the production of antibodies against self-antigens and triggering an over-active inflammatory response (Hui-Yuen et al 2016 ). Since impaired B cells are typical characteristics of SLE and B cells are the main cells involved in humoral immunity (Bakshi et al 2018 ), this implies that in ES-LUAD patients, the occurrence of rapid recurrence may be closely related to humoral immunity.…”

Section: Discussionmentioning

confidence: 99%

Microarray analysis of the expression profile of immune-related gene in rapid recurrence early-stage lung adenocarcinoma

Liu

Yang

Zhang

et al. 2020

J Cancer Res Clin Oncol

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Background Although much progress has been made in the diagnosis of early-stage lung adenocarcinoma (ES-LUAD), the prognosis for ES-LUAD patients with rapid recurrence is still poor. Importantly, there is currently no effective and precise method to screen patients who may develop rapid recurrence. Therefore, it is necessary to identify potential differentially expressed genes (DEGs) in ES-LUAD patients with rapid recurrence and non-rapid recurrence. Methods Affymetrix GeneChip Human Transcriptome Array was used to identify DEGs between ES-LUAD patients with rapid recurrence and non-rapid recurrence. Rapid recurrence was defined as recurrence-free survival (RFS) ≦ 1 year and non-rapid recurrence was defined as RFS ≧ 3 years. The biological functions of the DEGs were analyzed by GO and KEGG pathway enrichment analyses. The protein–protein interaction (PPI) network of identified DEGs was conducted by STRING and Cytoscape software. The expression level of crucial hub genes and tumor-infiltrating lymphocytes (TILs) was verified by immunohistochemistry (IHC). Results A total of 416 DEGs were identified between ES-LUAD patients with and without rapid recurrence. The results of GO analysis revealed that 2 of the top 10 categories in the domain of cellular component, 2 of the top 10 in the domain of molecular function, and 9 of the top 10 in the domain of biological process were functionally related to immunity. The results of KEGG analysis showed that 6 of the top 8 pathways were functionally involved in immune regulation and inflammatory response. The PPI network analysis identified ten crucial nodal protein, including EGFR, MMP9, IL-1β, PTGS2, MMP1, and 5 histone proteins, which constituted 25 key interactions. IL-1β and PTGS2 expression were closely related to immunity and IHC analysis further revealed that low expression of IL-1β and PTGS2 is associated with rapid recurrence. Kaplan–Meier analysis further revealed that LUAD patients with lower IL-1β or PTGS2 expression had a worse RFS. When the TIL density of CD3 + , CD4 + , CD8 + and CD20 + subsets was less than 20%, ES-LUAD patients have a higher probability of rapid recurrence. Conclusion There were significant differences in the expression of immune-related genes between patients with rapid recurrence and patient with non-rapid recurrence. Immune-related genes such as IL-1β and PTGS2 and TIL density (20%) play important roles in rapid recurrence of ES-LUAD. This study provided a theoretical basis for distinguishing the two types of patients from an immunological perspective. Electronic supplementary material The online version of this article (10.1007/s00432-020-03287-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Microarray analysis of the expression profile of immune-related gene in rapid recurrence early-stage lung adenocarcinoma

Liu

Yang

Zhang

et al. 2020

J Cancer Res Clin Oncol

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“…45-48 For example, the phase III RCTs BLISS-52 and BLISS-76 found that BMB plus standard of care therapy significantly reduced the rate of disease flares, permitted lower corticosteroid doses and decreased serologic SLE activity when compared to placebo. 45–48…”

Section: Discussionmentioning

confidence: 99%

“…44 Although there is scant literature on the use of BMB in JSLE, improved clinical and serological outcomes were observed after BMB therapy, 32 corresponding with earlier adult studies. [45][46][47][48] For example, the phase III RCTs BLISS-52 and BLISS-76 found that BMB plus standard of care therapy significantly reduced the rate of disease flares, permitted lower corticosteroid doses and decreased serologic SLE activity when compared to placebo. [45][46][47][48] The use of BMB for JSLE in only one study 32 suggests that there is much more to be done for JSLE patients.…”

Section: Discussionmentioning

confidence: 99%

The effectiveness and safety of biological therapeutics in juvenile-onset systemic lupus erythematosus (JSLE): a systematic review

Peterknecht

Keasey

Beresford

2018

Lupus

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Objective To systematically review and summarize the available literature regarding the effectiveness and safety of biologics in the treatment of juvenile-onset systemic lupus erythematosus. Methods PubMed was systematically searched for relevant literature (2012–2017 inclusive) using the following criteria: (1) patients diagnosed with juvenile-onset systemic lupus erythematosus (≤18 years at diagnosis); (2) treatment with any biological agent; and (3) outcome measures assessing effectiveness and safety. Systematic literature reviews, meta-analyses, randomized controlled trials, cohort studies, case control studies, cross sectional surveys and case-series with ≥3 patients were included. Independent extraction of articles by two authors using predefined criteria was performed. The quality of each study was assessed using CASP tools and Oxford CEBM Levels of Evidence. Results Nine articles met inclusion criteria: six cohort studies, two case series and one pilot study, totalling 230 patients. All but one article reported the effects of rituximab, the other those of belimumab. Overall, patients had active disease refractory to standard of care regimens using corticosteroids and immunosuppressants. Available evidence for rituximab demonstrated improvements in disease activity, complement levels and anti-dsDNA titres accompanying a steroid-sparing effect. Conclusion Rituximab can be considered an effective treatment in juvenile-onset systemic lupus erythematosus patients with severe disease manifestations and/or refractory disease. Based on current evidence, use of belimumab in juvenile-onset systemic lupus erythematosus patients cannot be recommended. The long-term safety of these biological agents remains uncertain. Further prospective studies, ideally robust randomized controlled trials, are urgently needed to obtain more accurate data on the effectiveness and long-term safety of rituximab, belimumab and other biologics in juvenile-onset systemic lupus erythematosus.

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“…BLyS may increase the ability of autoreactive B cells to escape regulatory mechanisms and differentiate into autoantibody-secreting plasma cells [34]. Belimumab has been shown to be effective in autoantibody-positive adult SLE patients with moderately active disease whose clinical manifestations are predominantly mucocutaneous and/or musculoskeletal and emerging data confirms that pSLE patients with similar characteristics also respond favorably to belimumab, in particular, suggesting a potential role for belimumab as a steroid-sparing agent [35]. …”

Section: Introductionmentioning

confidence: 99%

An Update on Treatment and Management of Pediatric Systemic Lupus Erythematosus

Thakral

Klein‐Gitelman

2016

Rheumatol Ther

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Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disorder in which 20 % of patients are diagnosed in childhood. Childhood-onset SLE is associated with higher morbidity and mortality than adult-onset SLE. The aims of disease management with early immunosuppression are to decrease disease activity and improve quality of life. A multidisciplinary approach is necessary due to the complexity of lupus in pediatric patients. It is important to provide patients with high quality of care and to instill ownership of their disease process from a young age to prepare them to manage this life-long illness. This article reviews current management of SLE in children.

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Targeted B cell therapies in the treatment of adult and pediatric systemic lupus erythematosus

Cited by 23 publications

References 64 publications

Microarray analysis of the expression profile of immune-related gene in rapid recurrence early-stage lung adenocarcinoma

Microarray analysis of the expression profile of immune-related gene in rapid recurrence early-stage lung adenocarcinoma

The effectiveness and safety of biological therapeutics in juvenile-onset systemic lupus erythematosus (JSLE): a systematic review

An Update on Treatment and Management of Pediatric Systemic Lupus Erythematosus

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