Objective: Sirolimus is effective for treatment of acquired pure red cell aplasia (aPRCA). Nevertheless, the immunomodulatory effect of sirolimus on peripheral blood mononuclear cells (PBMCs) from aPRCA remains undetermined. This study aims to investigate the immunomodulatory effect of sirolimus using PBMCs transcriptomics of aPRCA patients.

Methods: PBMCs were isolated from treatment-naïve (n = 11) or sirolimus-sensitive aPRCA patients ((n = 11) and then underwent RNA-sequencing.

Results: A total of 4060 genes, including 1639 upregulated genes and 2421 downregulated genes were significantly dysregulated in sirolimus-sensitive aPRCA patients compared with treatment-naïve patients. The top ten dysregulated genes were SYTL5, VSNL1, LINC00707, BTBD17, LINC01954 AL445437.1, IGKV1-8, AC090826.1, PRAME and LINC00520, respectively. Among the identified biological processes significantly enriched by dysregulated genes, B-cell-mediated immunity and circulating immunoglobulin-mediated humoral immune responses are the top two dysregulated immune responses in aPRCA patients with sirolimus treatment. Additionally, TNF, CD40, HLA-DRB1, SERPING1, SERPING1, C1QA, IGLL5 and IGHV3-11 were the key modulator in B-cell-mediated immune or circulating immunoglobulin-mediated humoral immune responses in sirolimus-sensitive aPRCA patients.

Conclusion: We first provided evidence showing the immunomodulatory effect of sirolimus on PBMCs from patients with aPRCA. Sirolimus can modulate the B-cell-mediated immunity and circulating immunoglobulin-mediated humoral immune responses in aPRCA patients.

No relevant conflicts of interest to declare.

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2023
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