Role of Treg cells and TGF-ß1 in patients with systemic lupus erythematosus: a possible relation with lupus nephritis.

Regulatory T (Treg) cells play an important role in the maintenance of immune tolerance to self and in the pathogenesis of autoimmune disease. Transforming growth factor-beta 1(TGF-ß1) is a regulatory cytokine with pleiotropic properties in immune responses. This study was to investigate the role of Treg cells and TGF-ß1 in the pathogenesis of patients with lupus nephritis (LN). A total of 42 new-onset systemic lupus erythematosus patients and 22 healthy controls were enrolled. The proportion of Treg cells in peripheral blood mononuclear cells (PBMCs) was evaluated by flow cytometric analysis. The serum and urinary TGF-ß1 levels were measured by enzyme-linked immunosorbent assay (ELISA). The results demonstrated a significant decrease in the frequency of CD4(+)CD25(high) and CD4(+)CD25(+)FoxP3(+) T cells in LN patients. The concentration of serum TGF-ß1 was found decreased in SLE patients, while urinary TGF-ß1 levels were significantly higher in LN patients. Based on our results, decreased Treg cells were accompanied with lower serum TGF-ß1 levels and higher urinary TGF-ß1 levels in LN patients. TGF-ß1 levels in serum may play a key role in the pathogenesis of renal impairment while the significantly increased urinary TGF-ß1 levels may be used as a biological marker in prediction of lupus nephritis.

Elevated Th17 cells are accompanied by FoxP3+ Treg cells decrease in patients with lupus nephritis.

To investigate the variations of T-helper 17 (Th17) and regulatory T (Treg) cells in patients with lupus nephritis (LN), a total of 60 systemic lupus erythematosus patients and 28 healthy controls (HCs) were enrolled. The frequency of Th17 cells and Treg cells in peripheral blood mononuclear cells (PBMCs) was evaluated by flow cytometric analysis. The serum concentrations of interleukin-17 (IL-17) and transforming growth factor-beta 1 (TGF-ß1) were measured by enzyme-linked immunosorbent assay (ELISA). The results demonstrated in LN patients a significant decrease in the frequency of CD4+CD25(high) and CD4+CD25+FoxP3+ T cells and a significant increase in the frequency of Th17 cells in peripheral blood, and the ratio of Th17 to Treg cell frequency was significantly increased along with increased SLEDAI scores. LN patients had a lower percentage and expression of FoxP3 in CD4+CD25(high) T cells than SLE patients without nephritis. The concentration of TGF-ß1 was found decreased in SLE patients compared with that from healthy controls, though no significant difference was found between LN patients and SLE patients without nephritis. The expression of IL-17 levels in LN patients exhibited a significant increase compared with patients without nephritis and healthy controls. Based on our results, the significantly elevated Th17 cells are accompanied by FoxP3+ Treg cells decrease in lupus nephritis, suggesting that Th17/Treg functional imbalance may be involved in the pathogenesis of renal damage in SLE patients.

Tofacitinib with conventional synthetic disease-modifying antirheumatic drugs in Chinese patients with rheumatoid arthritis: Patient-reported outcomes from a Phase 3 randomized controlled trial.

AIM: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We assess the effect of tofacitinib + conventional synthetic disease-modifying anti rheumatic drugs (csDMARDs) on patient-reported outcomes in Chinese patients with RA and inadequate response to DMARDs. METHODS: This analysis of data from the Phase 3 study ORAL Sync included Chinese patients randomized 4 : 4 : 1 : 1 to receive tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, placebo→tofacitinib 5 mg twice daily, or placebo→tofacitinib 10 mg twice daily, with csDMARDs. Placebo non-responders switched to tofacitinib at 3 months; the remaining placebo patients switched at 6 months. Least squares mean changes from baseline were reported for Health Assessment Questionnaire-Disability Index (HAQ-DI), patient assessment of arthritis pain (Pain), patient global assessment of disease activity (PtGA), physician global assessment of disease activity (PGA), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scores, Short Form 36 (SF-36), and Work Limitations Questionnaire (WLQ), using a mixed-effects model for repeated measures. RESULTS: Overall, 216 patients were included (tofacitinib 5 mg twice daily, n = 86; tofacitinib 10 mg twice daily, n = 86; placebo→tofacitinib 5 mg twice daily, n = 22; placebo→tofacitinib 10 mg twice daily, n = 22). At month 3, tofacitinib elicited significant improvements in HAQ-DI, Pain, PtGA, PGA and SF-36 Physical Component Summary scores. Improvements were generally maintained through 12 months. CONCLUSION: Tofacitinib 5 and 10 mg twice daily + csDMARDs resulted in improvements in health-related quality of life, physical function and Pain through 12 months in Chinese patients with RA.

[Study on the time selection of pregnancy and delivery in women with systemic lupus erythematosus].

OBJECTIVE: To analyze the appropriate time selection of pregnancy and delivery in women with systemic lupus erythematosus (SLE). METHODS: Twenty-nine pregnancies in women with SLE in our hospital from 1998 to 2003 were retrospectively analyzed regarding the selection of appropriate time of pregnancy and delivery. RESULTS: All patients did not take any cytotoxic medicine for at least 6 months before pregnancy. Twenty-three conceptions occurred when SLE was inactive for at least 1 year. Two conceptions occurred when SLE was active without doctors' agreement. SLE was diagnosed during pregnancy in the remaining 4 cases. The condition of all patients fluctuated and the gestational time at delivery ranged from 30 to 38 weeks after we modified the doses of glucocorticoid (prednisone). Among totally 29 living neonates, eight were premature neonates, three were FGR and one had serious congenital heart disease. Two neonates died of complications in early stage of neonatal period. None of the 29 neonates from all patients had neonatal lupus. CONCLUSION: Pregnancy safety will be improved obviously if the condition of SLE is controlled and the patients are given reasonable doses of glucocorticoid and intensive monitoring. If pharmacotherapy does not work well and the condition threatens the safety of mother and fetus, or the fetus has matured, termination of pregnancy should be done on time, which reduces maternal complications and improves the perinatal mortality rate. The gestational time should be 34 to 38 weeks.