Treg gene signatures predict and measure type 1 diabetes trajectory

Pesenacker, Anne M.; Chen, Virginia; Gillies, Jana; Speake, Cate; Marwaha, Ashish; Sun, Annika C.; Chow, Samuel; Tan, Rusung; Elliott, Thomas; Dutz, Jan P.; Tebbutt, Scott J.; Levings, Megan K.

doi:10.1172/jci.insight.123879

Cited by 28 publications

(35 citation statements)

References 23 publications

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“…The miRNA assay was conducted using the Exiqon qPCR platform as described previously (24). The Treg transcript assay was performed using the NanoString platform as described previously (14,17), with samples for the Treg assay sorted concomitantly with the cell subset RNA-Seq sample set. The proinsulin/C-peptide assay was conducted using a trefoil time-resolved fluorescence immunoassay (31), adapted to an AutoDelfia automatic system (PerkinElmer) (18).…”

Section: Methodsmentioning

confidence: 99%

“…In recent studies of individual assays, this heterogeneity has been suggested to predict the rate of progression after diagnosis for some subjects (12)(13)(14)(15). Better fundamental knowledge of the array of immune drivers of disease could help explain the differing rates of loss of β cells observed across subjects and potentially indicate immunotherapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

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A composite immune signature parallels disease progression across T1D subjects

et al. 2019

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Conflict of interest: EW receives a salary from Celgene, Inc. JMO receives a salary from Gilead Sciences, Inc. MKL has received research support from TxCell, Pfizer, and Bristol Myers Squibb and has patents pending related to alloantigen-specific chimeric antigen receptors (PCT/CA2018/051167 and PCT/CA2018/051174). PSL receives research support from Bristol Myers Squibb and is an inventor on patent US5844095A, "CTLA4Ig fusion proteins." RG has received consulting income from Juno Therapeutics, Takeda, Infotech Soft, and Celgene, Inc., and has received research support from Janssen Pharmaceuticals and Juno Therapeutics.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A composite immune signature parallels disease progression across T1D subjects

et al. 2019

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“…Special protections also exist in the United States for certain areas in the pharmaceutical market, such as those granted under the Orphan Drug Act of 1983 (ODA), which grants financial subsidies and market exclusivities for the development of drugs for rare and genetic diseases (Lazonick and Tulum, 2011). The ODA has until now not been an important factor in insulin pricing, though this may well change with the era of precision medicine and research exploring genetic risk factors in type-1 diabetes patients (Brissova et al, 2018;Mattner et al, 2019;Pesenacker et al, 2019).…”

Section: How Much Has the Price Of Insulin Changed In Recent Years?mentioning

confidence: 99%

Profits, Innovation and Financialization in the Insulin Industry

Collington

2020

INET Working Paper Series

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The list prices of analogue insulin medicines in the United States have soared during the past decade. In the wake of high-profile cases of prescription medicine “price-gouging”, such as Mylan’s EpiPen and Turing-acquired Daraprim, actors across the insulin supply chain are today facing growing scrutiny from US lawmakers and the wider public. For the most part, however, the role of shareholders in the insulin supply chain has been overlooked. This paper considers the relationship between profits realized from higher insulin list prices, pharmaceutical innovation, and the financial structures of the three dominant insulin manufacturing companies, which set list prices. It shows that despite claims to the contrary, insulin manufacturers extracted vast profits from the sale of insulin products in the period 2009-2018, as insulin list prices rose. Distributions to the company shareholders in the form of cash dividends and share repurchases totaled $122 billion over this period. The paper also considers the role of other actors in the insulin supply chain, such as pharmacy benefits managers (PBMs), in the determination of list prices. The data and analysis presented in the paper indicates that financialization could be considered in tension with not only the development of new drugs that will be available to patients in the future, but also the affordability of products that already exist today.

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“…However, the question still remains how those can help us in stratifying patients with HF and finding patient‐specific therapies. Immune profiles, signatures or ratios (Treg/Teff; proinflammatory/antiinflammatory monocytes) better reflect the immune status and do not restrict on one specific marker or target, which, due to redundancy of inflammation, may be compensated via other inflammatory signaling pathways. Therefore, stratification of patients with HF based on systemic or cardiac (in case of patients with inflammatory cardiomyopathy) immune profiles, signatures, or ratios, rather than on sole biomarkers, may be the future way to go.…”

Section: Refinement and Future Perspectivesmentioning

confidence: 99%

The Quest for Antiinflammatory and Immunomodulatory Strategies in Heart Failure

Linthout

Tschöpe

2019

Clin Pharma and Therapeutics

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Intensive research over the last 3 decades has unequivocally demonstrated the relevance of inflammation in heart failure (HF). Despite our current and ever increasing knowledge about inflammation, the clinical success of antiinflammatory and immunomodulatory therapies in HF is still limited. This review outlines the complexity and diversity of inflammation, its reciprocal interaction with HF, and addresses future perspectives, calling for immunomodulatory therapies that are specific for factors that activate the immune system without the risk of nonspecific immune suppression.

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Treg gene signatures predict and measure type 1 diabetes trajectory

Cited by 28 publications

References 23 publications

A composite immune signature parallels disease progression across T1D subjects

A composite immune signature parallels disease progression across T1D subjects

Profits, Innovation and Financialization in the Insulin Industry

The Quest for Antiinflammatory and Immunomodulatory Strategies in Heart Failure

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