mTOR pathway regulates the differentiation of peripheral blood Th2/Treg cell subsets in patients with pemphigus vulgaris.

Pemphigus vulgaris (PV) is a chronic and potentially life-threatening autoimmune blistering disease. Aberrant mTOR pathway activity is involved in many autoimmune diseases. This study investigated the correlation of mTOR pathway (PI3K/AKT/mTOR/p70S6K) activity with the loss of balance in T helper 2/regulatory T (Th2/Treg) cells in the peripheral blood of PV patients. CD4+ T cells were isolated from 15 PV patients and 15 healthy controls (HCs), the ratios of Th2/CD4+ T cells and Treg/CD4+ T cells, the activity of the mTOR pathway (PI3K/AKT/mTOR/p70S6K), the transcription factors and cytokines of Th2 and Treg cells were detected. Primary CD4+ T cells from PV patients were cultured under Th2- or Treg-polarizing conditions with or without rapamycin in vitro. We found that PV patients showed significantly elevated serum IL-4 when compared with HCs, and serum IL-4 level was positively correlated with the titer of anti-Dsg1/3 antibody and disease severity, while the serum TGF-ß level was negatively correlated with the titer of anti-Dsg3 antibody and disease severity. Meanwhile, PV patients showed increased Th2/CD4+ T cell ratio; decreased Treg/CD4+ T cell ratio; elevated mRNA of PI3K, AKT, mTOR and protein of PI3K (P85), AKT, p-AKT (Ser473), mTOR, p-mTOR (Ser2448), p-p70S6K (Thr389), GATA3; reduced protein of forkhead box protein 3. Rapamycin inhibited Th2 cell differentiation and promoted Treg cell differentiation in vitro. These data suggest a close association between mTOR pathway activation and the loss of balance in Th2/Treg cells in peripheral blood of PV patients. Inhibiting mTORC1 can help restore the Th2/Treg balance.

Short-Term Intravenous Infusion of Cyclophosphamide in the Treatment of Refractory Pemphigus Vulgaris: A Retrospective Study.

BACKGROUND: Pemphigus is an autoimmune disease of the skin and mucous membranes. Glucocorticoids have been the most effective drug for the treatment of pemphigus; however, some patients are insensitive to glucocorticoid therapy. Cyclophosphamide has been extensively used in the treatment of pemphigus. OBJECTIVES: To observe and evaluate the efficacy and safety of high-dose glucocorticoid with weekly intravenous cyclophosphamide in the treatment of refractory pemphigus vulgaris insensitive to glucocorticoids. METHODS: Clinical data of 19 patients with refractory pemphigus vulgaris (insensitive to glucocorticoid) who were treated with high-dose glucocorticoids(1.5 mg/kg/day prednisone) and weekly intravenous infusion of cyclophosphamide, and 24 patients who were sensitive to glucocorticoid therapy received a medium dose of glucocorticoid alone (1 mg/kg/day prednisone) were retrospectively analyzed. RESULTS: By the time the disease was brought under control, the average total dose of cyclophosphamide was 2.02 g. Comparison between the glucocorticoid-insensitive and glucocorticoid-sensitive groups showed that the average time to disease control was 2.68 vs. 2 weeks, and the average daily dosage of steroid was 1.33 ± 0.53 vs. 0.90 ± 0.28 mg/kg. At the 12- and 18-month follow-ups, the recurrence rate of the glucocorticoid-insensitive group was significantly lower than that of the sensitive group (5.3 vs. 37.5%, 15.8 vs. 45.8%). No serious adverse reactions were observed. CONCLUSION: High-dose glucocorticoid plus weekly intravenous infusion of cyclophosphamide safely, effectively, and rapidly controlled the conditions of the patients with refractory pemphigus who were insensitive to glucocorticoids, shortened the duration of hospitalization, avoided the risk of complications that could be caused by further increasing the dose of glucocorticoids (>1.5 mg/kg/day), and lowered the recurrence rate within 18 months.

Autoimmune Thyroid Disease in Patients with Systemic Lupus Erythematosus: A 7-year Retrospective Study in China.

BACKGROUND: The study was a retrospective case-controlled study. We aimed to determine the clinical and laboratory features of systemic lupus erythematosus (SLE) and compared the features of autoimmune thyroid disease (AITD) with those of SLE. MATERIALS AND METHODS: The study included 38 patients with SLE with AITD (SLE-AITD) and 190 age- and gender-matched SLE patients. The distribution of sociodemographic and clinical factors was compared between the SLE-AITD and SLE groups using Chi-square tests for gender and t tests for others. Univariate and multivariate logistic regression models were used to identify factors associated with the prevalence of AITD among SLE patients. RESULTS: In univariate analysis, malar rash, oral ulcers, serositis, anti-double-stranded DNA antibody positivity (anti-dsDNA+), anti-Sjögren's syndrome type A antibodies (SSA), anti-Sjögren's syndrome type B antibodies (SSB), low complement 3 (C3), and low complement 4 (C4) were significantly different between the SLE-AITD and SLE groups. There were no significant differences among other clinical or laboratory features. In multivariate analysis, serositis (adjusted odds ratio [AOR], 3.64; P = 0.00), anti-dsDNA+ (AOR, 0.30; P = 0.01) and low C3 (AOR, 0.30; P = 0.02) were all associated with SLE-AITD. CONCLUSIONS: In our study, serositis was a risk factor for AITD, so we propose that AITD should be considered in lupus patients with serositis.