Restoring T-helper 17 cell/regulatory T-cell balance and decreasing disease activity by rapamycin and all-trans retinoic acid in patients with systemic lupus erythematosus

Chu, Yanfang; Zhao, Chunmiao; Zhang, B; Wang, X; Wang, Y; An, J.; Chen, J

doi:10.1177/0961203319877239

Cited by 21 publications

(14 citation statements)

References 32 publications

(42 reference statements)

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“…The imbalanced Th17/Treg ratio needs to responsible for the increased pro‐inflammatory response. It was proved that chloroquine, rapamycin and all‐trans retinoic acid could improve the development of SLE via balancing the percentage of Th17 and Treg cells 34,35 . In this present study, we found that CuIIb could upregulate the percentage of Treg cells, and downregulate the percentage of Th17 cells in SLE mouse model and lymphocytes in vitro.…”

Section: Discussionsupporting

confidence: 58%

Cucurbitacin IIb improved active chromatin‐induced systemic lupus erythematosus via balancing the percentage of Th17 and Treg cells

Dong

et al. 2020

Clin Exp Pharma Physio

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The pathogenesis of systemic lupus erythematosus (SLE) is closely associated with aberrant immune system. Here, the aim of our study was to explore the regulation of cucurbitacin IIb (CuIIb) to Th17/Treg cells in SLE. Compared with normal mice, the percentage of Treg cells was downregulated in SLE mouse model, and Th17 was upregulated. Meantime, the production of Treg‐related transcription factor (foxp3) in SLE model mouse was reduced, and the production of Th17‐related transcription factor (RORγt) was increased. After treatment with CuIIb, the percentage of Treg cells in SLE mice was partly upregulated, and Th17 cells percentage was downregulated. The expression of foxp3 and RORγt in SLE mice were promoted and inhibited by CuIIb treatment, respectively. SLE‐induced kidney injury also was improved by CuIIb treatment. In vitro, we demonstrated again that CuIIb upregulated the percentage of Treg cells in lymphocytes from SLE mice, and downregulated the percentage of Th17 cells. Highly expressed IL‐6 and IL17, and lowly expressed IL‐10 and TGF‐β in lymphocytes from SLE mice were repressed and facilitated by CuIIb treatment, respectively. Overall, our data proved that CuIIb improved kidney injury in SLE mice through balancing the percentage of Th17 and Treg cells. Our data provided a reliable evidence to support the potential of CuIIb in SLE treatment.

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Section: Discussionsupporting

confidence: 58%

Cucurbitacin IIb improved active chromatin‐induced systemic lupus erythematosus via balancing the percentage of Th17 and Treg cells

Dong

et al. 2020

Clin Exp Pharma Physio

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“…We included five studies by Lai et al ., 8 Eriksson et al ., 9 Fernandez et al ., 5 Yap et al ., 6 and Chu et al . 13 with a total of 127 patients ( Table 2 ). No severe adverse events were reported in these studies.…”

Section: Resultsmentioning

confidence: 99%

Clinical efficacy and safety of sirolimus in systemic lupus erythematosus: a real-world study and meta-analysis

Peng

Hong

et al. 2020

Therapeutic Advances in Musculoskeletal

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Objective: To provide real-world data and summarize current clinical evidence on the efficacy and safety of sirolimus in active systemic lupus erythematosus (SLE) patients. Methods: This was a prospective real-world clinical study. Included SLE patients should have Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) ⩾ 2. They were treated with sirolimus and followed up regularly. The SLEDAI-2K, Physician Global Assessment (PGA), serological activity indices, and remission of organ manifestations were evaluated. We also performed a meta-analysis to integrate current evidence of sirolimus in SLE. Results: A total of 49 patients were included in the final analysis. After treatment, the SLEDAI-2K (6.2 ± 3.1 versus 4.0 ± 3.4, p = 0.001) decreased significantly, and the prednisone dosage was tapered successfully (9.9 ± 8.8 mg/day versus 5.9 ± 4.0 mg/day, p = 0.002). Serological activity indices also improved [complement 3 (C3): 0.690 ± 0.209 g/l versus 0.884 ± 0.219 g/l, p < 0.001; complement 4: 0.105 ± 0.059 g/l versus 0.141 ± 0.069 g/l, p < 0.001; anti-dsDNA antibody, 200 ± 178 IU/ml versus 156 ± 163 IU/ml, p = 0.022]. The remission proportions of arthritis, skin rash, and thrombocytopenia were 100%, 88.8%, and 46.2%, respectively. A total of 41.2% of lupus nephritis (LN) patients achieved renal remission, but the average 24-h urine protein level was not significantly changed. Meta-analysis enrolled five studies with 149 patients included, and revealed similar results regarding the changes of SLEDAI-2K [−3.5 (−5.0, −2.1)], C3 [0.224 (0.136, 0.311) g/l] and daily dosage of prednisone [−12.7 (−19.9, −5.6) mg/day]. Conclusion: Sirolimus might be effective and tolerated in SLE. The role of sirolimus in LN requires further study.

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“… demonstrated the lowest expression of lesional IL‐17A as well as transforming growth factor‐β and IL‐22 in ADTA among all AA cohorts. Imbalance between Th17 and regulatory T cells (Treg) has been implicated in many inflammatory diseases, and Treg have been shown to contribute to the improvement of AA . Prediction of sADTA may become more reliable, when the measurement of local Th17/Treg status is integrated, however, considering that the scoring system needs to be readily usable in clinics, such an approach would be impractical.…”

Section: Discussionmentioning

confidence: 99%

Elucidation of demographic, clinical and trichoscopic features for early diagnosis of self‐healing acute diffuse and total alopecia

Fukuyama

Kinoshita‐Ise

Sato

et al. 2020

The Journal of Dermatology

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The term "acute diffuse and total alopecia" (ADTA) has been often used as a synonym for self-regressing severe alopecia areata (AA). However, ADTA is originally defined as a rapidly-progressive subtype of AA (RP-AA) with short recovery time and favorable prognosis irrespective of interventions. Indeed, a subpopulation of ADTA recovers spontaneously. We focused on this unique subset of AA, which we coined as "self-healing ADTA" (sADTA). Prompt and accurate differentiation of sADTA from other RP-AA is important to avoid unnecessary treatments, which is still challenging due to the lack of predictive diagnostic hallmarks. In this study, 18 sADTA patients were retrospectively analyzed to delineate their demographics and clinical features, including gentle hair pull test and trichoscopic findings, followed by statistical comparison with those of RP-AA. All sADTA cases were female and the average age was 38.1 AE 15.9 years. The progression of hair loss areas peaked at 3.6 AE 1.5 months, and complete hair regrowth was achieved in 7.9 AE 1.7 months. The identified factors supporting the diagnosis of sADTA included being female; the absence of scalp pain and itch; the absence of extra-scalp hair loss; club hair predominance in hair pull test; predominant short vellus hairs; and increase in vacant follicular ostia on trichoscopy. Subsequently, a scoring system for early diagnosis of sADTA was developed by counting the number of six identified factors present in a tested case. When analyzed by the developed system, all sADTA cases, including an additional four cases, had scores of 4 or above, while all RP-AA cases had scores below 3 except one case. Therefore, the system successfully differentiated sADTA from RP-AA (P < 0.01). Despite some technical limitations, the current study suggested that sADTA is a distinctive entity with unique pathophysiology and that early diagnosis before intervention is feasible based on the characteristics.

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Restoring T-helper 17 cell/regulatory T-cell balance and decreasing disease activity by rapamycin and all-trans retinoic acid in patients with systemic lupus erythematosus

Cited by 21 publications

References 32 publications

Cucurbitacin IIb improved active chromatin‐induced systemic lupus erythematosus via balancing the percentage of Th17 and Treg cells

Cucurbitacin IIb improved active chromatin‐induced systemic lupus erythematosus via balancing the percentage of Th17 and Treg cells

Clinical efficacy and safety of sirolimus in systemic lupus erythematosus: a real-world study and meta-analysis

Elucidation of demographic, clinical and trichoscopic features for early diagnosis of self‐healing acute diffuse and total alopecia

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