Pacritinib abrogates the lupus phenotype in ABIN1[D485N] mice

帕克里替尼可消除 ABIN1[D485N] 小鼠的狼疮表型

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作者:Tsvetana Petrova, Clara Figueras-Vadillo, Sambit K Nanda, Cheryl Scudamore, Philip Cohen

Conclusions

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

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.

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.

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.

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