Abstract
The microbiota has been observed altered in autoimmune diseases, including idiopathic inflammatory myopathies (IIMs), and associated with different treatments. Low-dose IL-2 treatment emerges as a new option for active IIMs. This study aims to explore the role of low-dose IL-2 in regulating intestinal dysbiosis involved in the IIMs. In this study, 13 patients with active IIMs were enrolled and received 1 ×106 IU of IL-2 subcutaneously every other day for 12 weeks plus standard care. The clinical response and immune response were assessed. Stool samples were obtained to explore the structural and functional alterations of the fecal microbiota targeting the V3–V4 region of the 16S rRNA gene and analyze their associations with clinical and immunological characteristics. Our study demonstrated that diversity of microbiota decreased remarkably in patients with IIMs, compared to healthy controls. The inflammatory-related bacteria, such as Prevotellaceae increased, while some butyrate-producing bacteria, such as Pseudobutyrivibrio, Lachnospiraceae, Roseburia, and Blautia, decreased significantly. The alteration associated with disease activities in patients with IIMs. After low-dose IL-2 treatment, 92.31% (12/13) of patients achieved IMACS DOI at week 12. Proportion of Treg cells significantly increased at week 12 compared with that in baseline (15.9% [7.73, 19.4%] vs. 9.89% [6.02, 11.8%], P = 0.015). Interestingly, certain butyrate-producing bacteria increase significantly after IL-2 treatment, like Lachnospiraceae, Pseudobutyrivibrio, etc., and are associated with a rise in L-Asparagine and L-Leucine. The effects of low-dose IL-2 on gut microbiota were more apparent in NOD mice. Together, the data presented demonstrated that low-dose IL-2 was effective in active IIMs and highlighted the potential for modifying the intestinal microbiomes of dysbiosis to treat IIMs.
Highlights
The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune disorders characterized by myositis and multisystemic involvement, which includes dermatomyositis (DM), antisynthetase syndrome (ASS), inclusion body myositis (IBM), and immune-mediated necrotizing myopathy (IMNM) (Mariampillai et al, 2018)
Seventy-eight fecal samples were collected from 13 IIM patients and 52 healthy controls. 4,882,310 high-quality sequences were kept for further bioinformatic analysis after filtering low-quality sequences and the redundant sequences. 4248 amplicons were generated and were subjected to denoise and filtering chimeras with reference of Sliva_16s_v123.fa (Edgar, 2016). 2232 amplicon sequence variants (ASVs) have been identified for the generation of the ASV table
The IIMs are a heterogeneous group of chronic muscle disorders with therapeutic challenges
Summary
The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune disorders characterized by myositis and multisystemic involvement, which includes dermatomyositis (DM), antisynthetase syndrome (ASS), inclusion body myositis (IBM), and immune-mediated necrotizing myopathy (IMNM) (Mariampillai et al, 2018). Conventional treatment for IIMs includes glucocorticoids and immunosuppressants that are associated with substantial side effects (Oddis and Aggarwal, 2018). Several studies have shown that the low-dose interleukin (IL-2) can regulate cellular immunity and promote immunological balance (Feng et al, 2019). The clinical trial suggested that low-dose IL-2 is effective in treating IIMs (Miao et al, 2021). Several studies have demonstrated that gut microbiomes may be one of the most important contributors to the pathogenesis of rheumatic diseases. The effect of gut microbiota in IIMs has not been thoroughly studied
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