Therapeutic administration of etoposide coincides with reduced systemic HMGB1 levels in macrophage activation syndrome

Palmblad, Karin; Schierbeck, Hanna; Sundberg, Erik; Horne, AnnaCarin; Harris, Helena Erlandsson; Henter, Jan‐Inge; Andersson, Ulf

doi:10.1186/s10020-021-00308-0

Cited by 11 publications

(4 citation statements)

References 51 publications

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“…HMGB1 is a damage associated molecular pattern (DAMP), which has been studied in a series of inflammatory diseases, including JIA. Highly increased levels of HMGB1 have also been reported during MAS [ 16 ]. Since HMGB1 was not included in the PEA inflammation panel, HMGB1 levels were determined by ELISA.…”

Section: Resultsmentioning

confidence: 99%

Immunoprofiling of active and inactive systemic juvenile idiopathic arthritis reveals distinct biomarkers: a single-center study

Sundberg

Aulin

et al. 2021

Pediatr Rheumatol

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Background This study aimed to perform an immunoprofiling of systemic juvenile idiopathic arthritis (sJIA) in order to define biomarkers of clinical use as well as reveal new immune mechanisms. Methods Immunoprofiling of plasma samples from a clinically well-described cohort consisting of 21 sJIA patients as well as 60 age and sex matched healthy controls, was performed by a highly sensitive proteomic immunoassay. Based on the biomarkers being significantly up- or down-regulated in cross-sectional and paired analysis, related canonical pathways and cellular functions were explored by Ingenuity Pathway Analysis (IPA). Results The well-studied sJIA biomarkers, IL6, IL18 and S100A12, were confirmed to be increased during active sJIA as compared to healthy controls. IL18 was the only factor found to be increased during inactive sJIA as compared to healthy controls. Novel factors, including CASP8, CCL23, CD6, CXCL1, CXCL11, CXCL5, EIF4EBP1, KITLG, MMP1, OSM, SIRT2, SULT1A1 and TNFSF11, were found to be differentially expressed in active and/or inactive sJIA and healthy controls. No significant pathway activation could be predicted based on the limited factor input to the IPA. High Mobility Group Box 1 (HMGB1), a damage associated molecular pattern being involved in a series of inflammatory diseases, was determined to be higher in active sJIA than inactive sJIA. Conclusions We could identify a novel set of biomarkers distinguishing active sJIA from inactive sJIA or healthy controls. Our findings enable a better understanding of the immune mechanisms active in sJIA and aid the development of future diagnostic and therapeutic strategies.

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Section: Resultsmentioning

confidence: 99%

Immunoprofiling of active and inactive systemic juvenile idiopathic arthritis reveals distinct biomarkers: a single-center study

Sundberg

Aulin

et al. 2021

Pediatr Rheumatol

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“…Based on experience in pHLH, the topoisomerase inhibitor etoposide has been used in IEC-HS, and is considered by some to be second-line [ 8 , 90 ]. Etoposide abrogates effector cell activity through induction of apoptosis rather than more inflammatory cell death mechanisms like pyroptosis [ 142 , 143 ]. However, avoidance of effector cell destruction is of course beneficial if possible, and etoposide causes increased risk of secondary malignancies.…”

Section: Immune Effector Cell-associated Hlh-like Syndromementioning

confidence: 99%

Riding the storm: managing cytokine-related toxicities in CAR-T cell therapy

Hughes,

Teachey,

Diorio

2024

Semin Immunopathol

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The advent of chimeric antigen receptor T cells (CAR-T) has been a paradigm shift in cancer immunotherapeutics, with remarkable outcomes reported for a growing catalog of malignancies. While CAR-T are highly effective in multiple diseases, salvaging patients who were considered incurable, they have unique toxicities which can be life-threatening. Understanding the biology and risk factors for these toxicities has led to targeted treatment approaches which can mitigate them successfully. The three toxicities of particular interest are cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and immune effector cell-associated hemophagocytic lymphohistiocytosis (HLH)-like syndrome (IEC-HS). Each of these is characterized by cytokine storm and hyperinflammation; however, they differ mechanistically with regard to the cytokines and immune cells that drive the pathophysiology. We summarize the current state of the field of CAR-T-associated toxicities, focusing on underlying biology and how this informs toxicity management and prevention. We also highlight several emerging agents showing promise in preclinical models and the clinic. Many of these established and emerging agents do not appear to impact the anti-tumor function of CAR-T, opening the door to additional and wider CAR-T applications.

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“…Karin Palmblad et al. found that the use of etoposide can lead to clinical improvement coinciding with a decline of systemic HMGB1, IL-18, IFN-γ, and ferritin levels ( 141 ). Although there is some evidence that this drug may aggravate the infection or make it easier to develop new infections, its benefits are obviously greater ( 140 ).…”

Section: The Attractive Therapeutic Approach To Prevent Mas In Covid-19mentioning

confidence: 99%

Advances in attractive therapeutic approach for macrophage activation syndrome in COVID-19

et al. 2023

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Nowadays, people have relaxed their vigilance against COVID-19 due to its declining infection numbers and attenuated virulence. However, COVID-19 still needs to be concern due to its emerging variants, the relaxation of restrictions as well as breakthrough infections. During the period of the COVID-19 infection, the imbalanced and hyper-responsive immune system plays a critical role in its pathogenesis. Macrophage Activation Syndrome (MAS) is a fatal complication of immune system disease, which is caused by the excessive activation and proliferation of macrophages and cytotoxic T cells (CTL). COVID-19-related hyperinflammation shares common clinical features with the above MAS symptoms, such as hypercytokinemia, hyperferritinemia, and coagulopathy. In MAS, immune exhaustion or defective anti-viral responses leads to the inadequate cytolytic capacity of CTL which contributes to prolonged interaction between CTL, APCs and macrophages. It is possible that the same process also occurred in COVID-19 patients, and further led to a cytokine storm confined to the lungs. It is associated with the poor prognosis of severe patients such as multiple organ failure and even death. The main difference of cytokine storm is that in COVID-19 pneumonia is mainly the specific damage of the lung, while in MAS is easy to develop into a systemic. The attractive therapeutic approach to prevent MAS in COVID-19 mainly includes antiviral, antibiotics, convalescent plasma (CP) therapy and hemadsorption, extensive immunosuppressive agents, and cytokine-targeted therapies. Here, we discuss the role of the therapeutic approaches mentioned above in the two diseases. And we found that the treatment effect of the same therapeutic approach is different.

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Therapeutic administration of etoposide coincides with reduced systemic HMGB1 levels in macrophage activation syndrome

Cited by 11 publications

References 51 publications

Immunoprofiling of active and inactive systemic juvenile idiopathic arthritis reveals distinct biomarkers: a single-center study

Immunoprofiling of active and inactive systemic juvenile idiopathic arthritis reveals distinct biomarkers: a single-center study

Riding the storm: managing cytokine-related toxicities in CAR-T cell therapy

Advances in attractive therapeutic approach for macrophage activation syndrome in COVID-19

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