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 languageEnglish
Article numbere000822
Number of pages6
JournalLupus Science & Medicine
Volume10
Issue number1
DOIs
Publication statusPublished - 23 Feb 2023

Keywords

  • Autoimmune Diseases
  • Lupus Erythematosus, Systemic
  • Lupus Nephritis

ASJC Scopus subject areas

  • Rheumatology

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