Interleukin-1 in monocyte activation phenotypes in systemic juvenile idiopathic arthritis: Observations from a clinical trial of rilonacept, an interleukin-1 inhibitor

Yujuan Zhang; Saloni Gupta; Alexandra Ilstad-Minnihan; Sashi Ayyangar; Arielle D. Hay; Virginia Pascual; Norman T. Ilowite; Claudia Macaubas; Elizabeth D. Mellins

doi:10.1016/j.clim.2018.06.005

Interleukin-1 in monocyte activation phenotypes in systemic juvenile idiopathic arthritis: Observations from a clinical trial of rilonacept, an interleukin-1 inhibitor

Yujuan Zhang, Saloni Gupta, Alexandra Ilstad-Minnihan, Sashi Ayyangar, Arielle D. Hay, Virginia Pascual, Norman T. Ilowite, Claudia Macaubas, Elizabeth D. Mellins

Pediatrics

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Systemic juvenile idiopathic arthritis (sJIA) is a childhood rheumatic disease of unknown origin. Dysregulated innate immunity is implicated in disease pathology. We investigated if IL-1 inhibition affects circulating cytokines and monocyte gene expression. CD14+ monocytes from patients in the RAPPORT trial were analyzed by RT-PCR for expression of IL1B and transcription factors associated with monocyte activation. Serum IL-1ra decreased with treatment, and IL-18BP transiently increased. Serum levels of IL-1β IL-6, IL-10 and IL-18 were unchanged. IRF5 and STAT6 were decreased, and PPARG was increased, independent of clinical response, and may represent a skew toward a PPARG-driven M2-like phenotype. IL1B expression was decreased in early clinical responders. A transient increase in STAT1, and a decrease in SOCS1 preceded the reduction in IL1B in early clinical responders. Changes in IL1B/STAT1/SOCS1 could be associated with crosstalk between IL-1 and IFN pathways in sJIA. These transcriptional changes might be useful as drug response biomarkers.

Original language	English (US)
Pages (from-to)	9-18
Number of pages	10
Journal	Clinical Immunology
Volume	194
DOIs	https://doi.org/10.1016/j.clim.2018.06.005
State	Published - Sep 2018

Keywords

Juvenile arthritis
Monocytes;cytokine

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1016/j.clim.2018.06.005

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Zhang, Y., Gupta, S., Ilstad-Minnihan, A., Ayyangar, S., Hay, A. D., Pascual, V., Ilowite, N. T., Macaubas, C., & Mellins, E. D. (2018). Interleukin-1 in monocyte activation phenotypes in systemic juvenile idiopathic arthritis: Observations from a clinical trial of rilonacept, an interleukin-1 inhibitor. Clinical Immunology, 194, 9-18. https://doi.org/10.1016/j.clim.2018.06.005

Zhang, Y, Gupta, S, Ilstad-Minnihan, A, Ayyangar, S, Hay, AD, Pascual, V, Ilowite, NT, Macaubas, C & Mellins, ED 2018, 'Interleukin-1 in monocyte activation phenotypes in systemic juvenile idiopathic arthritis: Observations from a clinical trial of rilonacept, an interleukin-1 inhibitor', Clinical Immunology, vol. 194, pp. 9-18. https://doi.org/10.1016/j.clim.2018.06.005

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abstract = "Systemic juvenile idiopathic arthritis (sJIA) is a childhood rheumatic disease of unknown origin. Dysregulated innate immunity is implicated in disease pathology. We investigated if IL-1 inhibition affects circulating cytokines and monocyte gene expression. CD14+ monocytes from patients in the RAPPORT trial were analyzed by RT-PCR for expression of IL1B and transcription factors associated with monocyte activation. Serum IL-1ra decreased with treatment, and IL-18BP transiently increased. Serum levels of IL-1β IL-6, IL-10 and IL-18 were unchanged. IRF5 and STAT6 were decreased, and PPARG was increased, independent of clinical response, and may represent a skew toward a PPARG-driven M2-like phenotype. IL1B expression was decreased in early clinical responders. A transient increase in STAT1, and a decrease in SOCS1 preceded the reduction in IL1B in early clinical responders. Changes in IL1B/STAT1/SOCS1 could be associated with crosstalk between IL-1 and IFN pathways in sJIA. These transcriptional changes might be useful as drug response biomarkers.",

keywords = "Juvenile arthritis, Monocytes;cytokine",

author = "Yujuan Zhang and Saloni Gupta and Alexandra Ilstad-Minnihan and Sashi Ayyangar and Hay, {Arielle D.} and Virginia Pascual and Ilowite, {Norman T.} and Claudia Macaubas and Mellins, {Elizabeth D.}",

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year = "2018",

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doi = "10.1016/j.clim.2018.06.005",

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AU - Ilstad-Minnihan, Alexandra

AU - Ayyangar, Sashi

AU - Hay, Arielle D.

AU - Pascual, Virginia

AU - Ilowite, Norman T.

AU - Macaubas, Claudia

AU - Mellins, Elizabeth D.

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N2 - Systemic juvenile idiopathic arthritis (sJIA) is a childhood rheumatic disease of unknown origin. Dysregulated innate immunity is implicated in disease pathology. We investigated if IL-1 inhibition affects circulating cytokines and monocyte gene expression. CD14+ monocytes from patients in the RAPPORT trial were analyzed by RT-PCR for expression of IL1B and transcription factors associated with monocyte activation. Serum IL-1ra decreased with treatment, and IL-18BP transiently increased. Serum levels of IL-1β IL-6, IL-10 and IL-18 were unchanged. IRF5 and STAT6 were decreased, and PPARG was increased, independent of clinical response, and may represent a skew toward a PPARG-driven M2-like phenotype. IL1B expression was decreased in early clinical responders. A transient increase in STAT1, and a decrease in SOCS1 preceded the reduction in IL1B in early clinical responders. Changes in IL1B/STAT1/SOCS1 could be associated with crosstalk between IL-1 and IFN pathways in sJIA. These transcriptional changes might be useful as drug response biomarkers.

AB - Systemic juvenile idiopathic arthritis (sJIA) is a childhood rheumatic disease of unknown origin. Dysregulated innate immunity is implicated in disease pathology. We investigated if IL-1 inhibition affects circulating cytokines and monocyte gene expression. CD14+ monocytes from patients in the RAPPORT trial were analyzed by RT-PCR for expression of IL1B and transcription factors associated with monocyte activation. Serum IL-1ra decreased with treatment, and IL-18BP transiently increased. Serum levels of IL-1β IL-6, IL-10 and IL-18 were unchanged. IRF5 and STAT6 were decreased, and PPARG was increased, independent of clinical response, and may represent a skew toward a PPARG-driven M2-like phenotype. IL1B expression was decreased in early clinical responders. A transient increase in STAT1, and a decrease in SOCS1 preceded the reduction in IL1B in early clinical responders. Changes in IL1B/STAT1/SOCS1 could be associated with crosstalk between IL-1 and IFN pathways in sJIA. These transcriptional changes might be useful as drug response biomarkers.

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KW - Monocytes;cytokine

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Interleukin-1 in monocyte activation phenotypes in systemic juvenile idiopathic arthritis: Observations from a clinical trial of rilonacept, an interleukin-1 inhibitor

Abstract

Keywords

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