Pacritinib abrogates the lupus phenotype in ABIN1[D485N] mice

Tsvetana Petrova; Clara Figueras-Vadillo; Sambit Nanda; Cheryl Scudamore; Philip Cohen

doi:10.1136/lupus-2022-000822

Pacritinib abrogates the lupus phenotype in ABIN1[D485N] mice

Tsvetana Petrova, Clara Figueras-Vadillo, Sambit Nanda, Cheryl Scudamore, Philip Cohen (Lead / Corresponding author)

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Abstract

Objective: The aim of the study was to investigate whether the IRAK1/JAK2/Flt3 inhibitor pacritinib prevents disease development in the lupus-prone ABIN1[D485N] knock-in mouse.

Methods: ABIN1[D485N] knock-in mice aged 8 weeks were fed for 10 weeks on a diet containing pacritinib. Body weight was monitored, and serum collected at the end to measure pacritinib, autoantibody and immunoglobulin levels. Splenic immune cell populations were analysed, and the kidney, liver and lungs examined for pathology.

Results: Pacritinib prevented multiple facets of the lupus phenotype in ABIN1[D485N] knock-in mice, including splenomegaly, expansion of splenic germinal centre B cells, follicular T helper cells, and neutrophils, elevated serum levels of double-stranded DNA antibodies and immunoglobulins, glomerular IgA and lung inflammation.

Conclusions: Pacritinib may be useful for the treatment of multiorgan inflammation in patients with lupus.

Original language	English
Article number	e000822
Number of pages	6
Journal	Lupus Science & Medicine
Volume	10
Issue number	1
DOIs	https://doi.org/10.1136/lupus-2022-000822
Publication status	Published - 23 Feb 2023

Keywords

Autoimmune Diseases
Lupus Erythematosus, Systemic
Lupus Nephritis

ASJC Scopus subject areas

Rheumatology

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10.1136/lupus-2022-000822Licence: CC BY-NC

Final Published VersionFinal published version, 11.1 MBLicence: CC BY-NC

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title = "Pacritinib abrogates the lupus phenotype in ABIN1[D485N] mice",

abstract = "Objective: The aim of the study was to investigate whether the IRAK1/JAK2/Flt3 inhibitor pacritinib prevents disease development in the lupus-prone ABIN1[D485N] knock-in mouse.Methods: ABIN1[D485N] knock-in mice aged 8 weeks were fed for 10 weeks on a diet containing pacritinib. Body weight was monitored, and serum collected at the end to measure pacritinib, autoantibody and immunoglobulin levels. Splenic immune cell populations were analysed, and the kidney, liver and lungs examined for pathology.Results: Pacritinib prevented multiple facets of the lupus phenotype in ABIN1[D485N] knock-in mice, including splenomegaly, expansion of splenic germinal centre B cells, follicular T helper cells, and neutrophils, elevated serum levels of double-stranded DNA antibodies and immunoglobulins, glomerular IgA and lung inflammation.Conclusions: Pacritinib may be useful for the treatment of multiorgan inflammation in patients with lupus.",

keywords = "Autoimmune Diseases, Lupus Erythematosus, Systemic, Lupus Nephritis",

author = "Tsvetana Petrova and Clara Figueras-Vadillo and Sambit Nanda and Cheryl Scudamore and Philip Cohen",

note = "Funding Information: The study was funded by CTI BioPharma Corp. Copyright: {\textcopyright} Author(s) (or their employer(s)) 2023.",

year = "2023",

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doi = "10.1136/lupus-2022-000822",

language = "English",

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AU - Petrova, Tsvetana

AU - Figueras-Vadillo, Clara

AU - Nanda, Sambit

AU - Scudamore, Cheryl

AU - Cohen, Philip

PY - 2023/2/23

Y1 - 2023/2/23

N2 - Objective: The aim of the study was to investigate whether the IRAK1/JAK2/Flt3 inhibitor pacritinib prevents disease development in the lupus-prone ABIN1[D485N] knock-in mouse.Methods: ABIN1[D485N] knock-in mice aged 8 weeks were fed for 10 weeks on a diet containing pacritinib. Body weight was monitored, and serum collected at the end to measure pacritinib, autoantibody and immunoglobulin levels. Splenic immune cell populations were analysed, and the kidney, liver and lungs examined for pathology.Results: Pacritinib prevented multiple facets of the lupus phenotype in ABIN1[D485N] knock-in mice, including splenomegaly, expansion of splenic germinal centre B cells, follicular T helper cells, and neutrophils, elevated serum levels of double-stranded DNA antibodies and immunoglobulins, glomerular IgA and lung inflammation.Conclusions: Pacritinib may be useful for the treatment of multiorgan inflammation in patients with lupus.

AB - Objective: The aim of the study was to investigate whether the IRAK1/JAK2/Flt3 inhibitor pacritinib prevents disease development in the lupus-prone ABIN1[D485N] knock-in mouse.Methods: ABIN1[D485N] knock-in mice aged 8 weeks were fed for 10 weeks on a diet containing pacritinib. Body weight was monitored, and serum collected at the end to measure pacritinib, autoantibody and immunoglobulin levels. Splenic immune cell populations were analysed, and the kidney, liver and lungs examined for pathology.Results: Pacritinib prevented multiple facets of the lupus phenotype in ABIN1[D485N] knock-in mice, including splenomegaly, expansion of splenic germinal centre B cells, follicular T helper cells, and neutrophils, elevated serum levels of double-stranded DNA antibodies and immunoglobulins, glomerular IgA and lung inflammation.Conclusions: Pacritinib may be useful for the treatment of multiorgan inflammation in patients with lupus.

KW - Autoimmune Diseases

KW - Lupus Erythematosus, Systemic

KW - Lupus Nephritis

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JF - Lupus Science & Medicine

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Pacritinib abrogates the lupus phenotype in ABIN1[D485N] mice

Abstract

Keywords

ASJC Scopus subject areas

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Elucidation of Mechanisms that Restrict Activation of the Innate Immune System to Prevent Inflammatory and Autoimmune Diseases

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Pacritinib abrogates the lupus phenotype in ABIN1[D485N] mice

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

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Elucidation of Mechanisms that Restrict Activation of the Innate Immune System to Prevent Inflammatory and Autoimmune Diseases

Cite this