MDR-1 and MRP-1 activity in peripheral blood leukocytes of rheumatoid arthritis patients

Micsik, Tamás; Lőrincz, András; Gál, János; Schwab, Richárd; Peták, István

doi:10.1186/s13000-015-0447-1

Cited by 18 publications

(12 citation statements)

References 20 publications

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“…Performing real‐time transporter activity measurements using fluorescent reporter substrates is highly beneficial in the clinical setting for personalized therapy and monitoring in certain hematologic malignancies and in autoimmune diseases, since the activities of MDR1, MRP1, and BCRP serve as biomarkers to predict the patient's response to small molecule therapy in treatment naïve conditions and during small molecule drug treatment . Furthermore, the determination of transporter activity is also relevant in cell lines in pharmaceutical research.…”

Section: Introductionmentioning

confidence: 99%

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

et al. 2019

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These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer‐reviewed by leading experts in the field, making this an essential research companion.

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Section: Introductionmentioning

confidence: 99%

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

et al. 2019

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“…In early RA, leukocytes invade the synovial joints followed by other pro-inflammatory mediators which instigate an inflammatory cascade and provoke synovitis (Smolen et al, 2018). Activated monocytes and T cells, both a source of proinflammatory cytokines such as TNF-a, can be found in peripheral blood (Batliwalla et al, 2005) and many RA studies have used peripheral blood cells to identify disease-related genes (Edwards et al, 2007;Micsik et al, 2015;Kuuliala et al, 2017;Li et al, 2020). The common therapy for the disease includes the use of Disease-modifying anti-rheumatic drugs (DMARDs).…”

Section: Introductionmentioning

confidence: 99%

Inference of an integrative, executable network for Rheumatoid Arthritis combining data-driven machine learning approaches and a state-of-the-art mechanistic disease map

Miagoux

Mezquita

Singh

et al. 2021

Preprint

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MotivationRheumatoid arthritis (RA) is a multifactorial autoimmune disease that causes chronic inflammation of the joints. RA is considered a complex disease as it involves various genetic, environmental, and epigenetic factors. Systems biology approaches provide the means to study complex diseases by integrating different layers of biological information. Combining multiple data types can help compensate for missing or conflicting information and limit the possibility of false positives. In this approach, we integrate three different biological layers (gene expression, signalling cascades, mutations), obtained by bottom-up and top-down methods to build an integrative, disease-specific network. The goal behind this endeavour is to see if we can unravel mechanisms governing the regulation of key genes identified as mutation carriers in RA and derive patient-specific models to gain more insights into the disease heterogeneity.ResultsIn this work, we combine biological data relevant to Rheumatoid Arthritis, in the form of a global, integrative network. We first make use of publicly available transcriptomic datasets (peripheral blood) relative to RA and machine learning to create an RA specific transcription factor (TF) co-regulatory network. The TF cooperativity network is subsequently enriched in signalling cascades and upstream regulators using prior knowledge encoded in a state-of-the-art, RA-specific molecular map. Lastly, a list of RA specific variants highlights key genes associated with known disease mutations.AvailabilityDatasets used for the analysis are publicly available. All scripts used to generate results and the Shiny app will be freely accessible after peer-reviewed publication.

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“…For example, one study found decreased functional activity of both MDR1 and MRP1 in peripheral blood leukocytes of RA patients compared to non-RA and healthy controls. 26 Another study found downregulation of MDR1 expression in during early stages of methotrexate treatment in patients with RA. 27 Part of this incongruence between MDR function and grade of inflammation could also be ascribed to the various endogenous functions of these transporters that include transport of several metabolites and signaling molecules, besides inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

Role of Multidrug Resistance Proteins in Nonresponders to Immunomodulatory Therapy for Noninfectious Uveitis

Tagirasa

Rana

Kaza

et al. 2020

Trans. Vis. Sci. Tech.

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Nearly a third to half of patients with noninfectious uveitis (NIU) fail to achieve control with immunomodulatory therapy (IMT). Multidrug resistance (MDR) proteins are transmembrane proteins that allow efflux of intracellular drugs, leading to drug resistance. The aim of our study was to compare MDR protein function in blood CD4 + cells between responders and nonresponders to IMT. Methods: We included NIU patients on IMT for ≥6 months and corticosteroid dose ≤10 mg/d. Nonresponders to treatment were those with worsening (two or more steps) of inflammation in the past 3 months on full-dose immunosuppressive therapy. MDR function was assessed by Rhodamine-123 dye retention in blood CD4 + cells. Three nonresponders were treated with adjunctive oral cyclosporine A (CSA, MDR inhibitor) therapy for 2 months and reevaluated. Results: Fourteen NIU patients were recruited. Most (n = 8) had Vogt-Koyanagi-Harada disease. These included nine nonresponders and five responders to IMT. Nonresponders produced significantly higher MDR function and proinflammatory cytokines (interferon γ , tumor necrosis factor α, interleukin 17, and Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)) than responders. In vitro CSA treatment of CD4 + cells inhibited MDR expression and proinflammatory cytokine production while increasing Foxp3. Finally, adjunctive oral CSA therapy led to improvement in clinical inflammatory scores with a concurrent decrease in MDR function and proinflammatory cytokine secretion. Conclusions: MDR function is significantly higher in CD4 + T cells of nonresponders to IMT. Adjunctive CSA therapy may decrease MDR function and allow improvement in treatment response to IMT. Translational Relevance: Our study highlights the need for MDR inhibition strategies in NIU patients not responding to IMT for improving the efficacy of anti-inflammatory therapy.

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MDR-1 and MRP-1 activity in peripheral blood leukocytes of rheumatoid arthritis patients

Cited by 18 publications

References 20 publications

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

Inference of an integrative, executable network for Rheumatoid Arthritis combining data-driven machine learning approaches and a state-of-the-art mechanistic disease map

Role of Multidrug Resistance Proteins in Nonresponders to Immunomodulatory Therapy for Noninfectious Uveitis

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