Low-dose IL-2 therapy invigorates CD8+ T cells for viral control in systemic lupus erythematosus.
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ABSTRACT:
SUBMITTER: Zhou P
PROVIDER: S-EPMC8525737 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
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Low-dose IL-2 therapy invigorates CD8+ T cells for viral control in systemic lupus erythematosus.
Zhou Pengcheng P Chen Jiali J He Jing J Zheng Ting T Yunis Joseph J Makota Victor V Alexandre Yannick O YO Gong Fang F Zhang Xia X Xie Wuxiang W Li Yuhui Y Shao Miao M Zhu Yanshan Y Sinclair Jane E JE Miao Miao M Chen Yaping Y Short Kirsty R KR Mueller Scott N SN Sun Xiaolin X Yu Di D Li Zhanguo Z
PLoS pathogens 20211007 10
Autoimmune diseases are often treated by glucocorticoids and immunosuppressive drugs that could increase the risk for infection, which in turn deteriorate disease and cause mortality. Low-dose IL-2 (Ld-IL2) therapy emerges as a new treatment for a wide range of autoimmune diseases. To examine its influence on infection, we retrospectively studied 665 patients with systemic lupus erythematosus (SLE) including about one third receiving Ld-IL2 therapy, where Ld-IL2 therapy was found beneficial in r ...[more]
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Project description:BackgroundLow-dose IL-2 (Ld-IL2) has shown favorable therapeutic effects in systemic lupus erythematosus (SLE) therapy. However, previous clinical trials reported an SLE Responder Index-4 (SRI-4) response rate of 65.52%-68%, with approximately half failing to achieve the primary endpoint by week 24. Our study aims to determine the real-world use of Ld-IL2 and to identify determinants of its effectiveness in SLE.MethodsWe pooled data from 342 SLE patients undergoing sequential Ld-IL2 treatment, with 314 persisting for over 3 months were included in effectiveness and prediction analyses. All patients were categorized into responder (n = 136) and non-responder group (n = 178) according to SRI-4. Lupus Low Disease Activity State (LLDAS) was also analyzed to validate our results.ResultsRash, lower complement 3 (C3), and renal involvement including urine protein, urine occult blood and urine casts emerged as prominent predictors of achieving SRI-4. Adjusting for baseline values using the ratio of change to baseline revealed significant differences in CD4 + T cell immune profiles between responders and non-responders. ROC analysis confirmed a satisfactory performance of rash, renal involvement, percentage change of CD4 + T cells, and C3 in predicting SRI-4, yielding an AUC of 0.933. LLDAS analysis showed that hematological involvements and lower CLA + Treg were potent predictive markers in LLDAS attainment. Conversely, renal involvement failed to have significant association in achieving LLDAS. The analysis of background therapy in SLE patients showed that MMF was more likely to reach the SRI-4 response with the combination of Ld-IL2.ConclusionsThese findings uncovered the predictors of Ld-IL2 treatment efficacy in SLE patients and provided guidance to physicians for rational utilization.
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Project description:Objectives We have reported previously that Belimumab, a human monoclonal antibody that inhibits B-cell activating factor(BAFF) could be an effective and safe option to treat Neuropsychiatric manifestations of SLE (NPSLE). To avoid inadequate efficacy of Belimumab and significant adverse events of often-used dose of cyclophosphamide (CYC) for SLE, we evaluated the efficacy, safety, and possible immune mechanisms of Belimumab treatment in combination with intermittent low-dose intravenous CYC for moderate-to-severe SLE. Methods In this non blinded and parallel-group trial, we collected 82 cases of moderate-to-severe SLE patients, 40 received Belimumab treatment and 42 received conventional treatments as historical controls for 24 weeks. The demographic features, clinical manifestations, and laboratory indicators including peripheral blood lymphocyte subgroups or subsets were compared before and after the treatments. Results Compared with the baseline, 6 months post Belimumab group treatment, disease activity score SLEDAI (13.78 to 3.82, P<0.05) and BILAG scores (16.40 to 5.48, P<0.05) were reduced; C3 (0.19 to 1.14, P<0.05) and C4 (0.04 to 0.22, P<0.05) increased; the absolute numbers of B and T cells were the first decreased and then significantly increased, tended to balance. Moreover, Belimumab group treatment significantly reduced the serum levels of IL-6, the ratio of B and T cells, and the proportion of infections and menstrual disorders. Conclusion Compared with conventional treatment, Belimumab with low-dose intravenous CYC significantly reduced disease activity scores and maintained the B/T cell balance for SLE patients at 24 weeks. It was more efficacy and safe (adverse events such as infection were significantly lower). It should be the mechanism that Belimumab combined with low-dose intravenous CYC therapy restores the balance of T and B cells, which proposes a potential treatment strategyfor SLE.
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Project description:IntroductionLow-dose interleukin-2 (IL-2) regulates the homeostasis of CD4+ T cells by modulating the proportions of effector and regulatory T cells, thus reducing disease activity in patients with systemic lupus erythematosus (SLE). However, to date, no research has been carried out on the efficacy of low-dose IL-2 for treating autoimmune thyroid disease (AITD). The aim of this study was to observe the effects of IL-2 on AITD patients with concurrent SLE, and explore potential mechanism of action.MethodsA retrospective analysis was conducted on 29 SLE patients with concurrent AITD. Among them, 11 patients were in IL-2 therapy group and 18 patients without IL-2 treatment were considered as control group. Two groups had similar disease activities and were treated with comparable regular strategy. Free triiodothyronine (FT3), free thyroxine (FT4), thyroxine(T4), triiodothyronine(T3), thyroid stimulating hormone (TSH), thyroglobulin antibody (TG-Ab), thyroid peroxidase antibody (TPO-Ab) levels and immune cell subgroups were measured.ResultsAfter receiving low-dose IL-2 therapy, the TG-Ab and TPO-Ab levels decreased drastically (TG-Ab p = 0.008, TPO-Ab p = 0.007), and the majority of the AITD patients became seronegative, while there was no discernible change in control group. In IL-2 group, percentage of CD4+ T cells showed a significant increase after treatment (p = 0.029), with an upward trend in the ratio of regulatory T (Treg) cells to follicular helper T (Tfh) cells (Treg/Tfh). The percentage as well as absolute count of B cells demonstrated a decreasing trend.ConclusionLow-dose IL-2 may downregulate the levels of TG-Ab and TPO-Ab by modulating the immune balance of Treg/Tfh and B-cells, providing new avenue for clinical treatment of AITD.
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