Objectives: This study evaluated the correlation between tumor necrosis factor alpha inhibitor (TNF-I) and interstitial lung disease (ILD) in rheumatoid arthritis (RA). We aimed to raise awareness and consummate therapy by summarizing the characteristics of the adverse events of ILD. Methods: A comprehensive search of the PubMed, Embase, Ovid, Cochrane, China National Knowledge Infrastructure, and Wanfang databases was performed from inception to November 2018. Statistical analysis of demographic characteristics, clinical features, and relative risks was performed using Microsoft Excel 2007 and SPSS version 20.0. Results: A total of 7 eligible articles and another 28 case reports were enrolled. The 7 cohort studies demonstrated the tendency that ILD cases might not benefit from TNF-I therapy. TNF-I might be associated with ILD adverse events. The case reports further confirmed these findings, as most (87.5%) of the cases showed that TNF-1 was harmful to patients with ILD and even resulted in a 35% mortality rate. Further investigation revealed that ILD adverse events tended to appear in female patients with a long RA history (p<0.05). The subgroup analysis suggested that early detection and precise treatment are key factors in determining survival or death when an ILD adverse event occurs. A large proportion of ILD adverse events (48.6%) appeared at 2.38±1.03 weeks after the infusion of infliximab. Conclusion: A fresh look at the evidence highlights that TNF-I might be associated with ILD adverse events in RA, which can induce more severe pulmonary symptoms and even result in death. Therefore, more attention should be paid to effective prevention, early diagnosis, and precise management. Notably, further prospective cohort studies are warranted to better interpret the association or causality between TNF-I and ILD.

High‐affinity antibodies are produced during multiple processes in germinal centres (GCs), where follicular helper T (Tfh) cells interact closely with B cells to support B‐cell survival, differentiation and proliferation. Recent studies have revealed that a specialised subset of regulatory T cells, follicular regulatory T (Tfr) cells, especially fine‐tune Tfh cells and GC B cells, ultimately regulating GC reactions. Alterations in frequencies or function of Tfr cells may result in multiple autoantibody‐mediated or autoantibody‐associated diseases. This review discusses recent insights into the physiology and pathology of Tfr cells, with a special emphasis on their potential roles in human diseases. Discrepancies are common among studies, reflecting the limited understanding of Tfr cells. Further exploration of the mechanisms of Tfr cells in these diseases and thus targeting Tfr cells may help reinstate immune homeostasis and provide novel immunotherapy.

Purpose: Total glucosides of paeony (TGP) have been confirmed to reduce hepatotoxicity caused by methotrexate (MTX) and leflunomide (LEF) in rheumatoid arthritis (RA). Nevertheless, high-quality evidence-based meta-analysis data on the issue are unavailable. This study aimed to evaluate the efficacy and safety of this combination treatment for RA. Materials and methods: PubMed, EMBASE, Web of Science, Cochrane Library, ClinicalTrials, Chinese Biomedical Literature database, China National Knowledge Internet, Wan Fang, and VIP were searched up to February 2019. Randomized controlled trials (RCTs) on the efficacy and safety of TGP combined MTX and LEF for RA were included. Results: Eight RCTs were included in the final meta-analysis. Pooled results showed better therapeutic effects against RA in the TGP-treated group (RR =1.10, 95% CI: 1.04 −1.16). The TGP+MTX+LEF group showed a reduced erythrocyte sedimentation rate (MD = −2.80 mm/h, 95% CI: −5.08 - −0.52), C-reactive protein level (MD = −4.17 mg/L, 95% CI: −7.84 - −0.51), and rheumatoid factor (MD = −12.09 IU/mL, 95% CI: −14.05 - −10.14). Besides, the combination treatment tended to benefit lipid profiles (total cholesterol: 95% CI: −1.27–0.06; triglycerides: 95% CI: −0.49 - −0.08; high-density lipoprotein cholesterol: 95% CI: 0.15–0.83; and low-density lipoprotein cholesterol: 95% CI: −0.54 - −0.02). Adverse events, hepatotoxicity in particular, significantly decreased (RR =0.55, 95% CI: 0.38–0.80) in the TGP group. Conclusion: Compared to MTX and LEF therapy, TGP combination treatment may be a more effective and safer strategy. It is advisable to apply TGP as an adjuvant given its hepatoprotective and possible lipid-regulating effect. However, further large-scale and high-quality clinical trials are warranted, and the efficacy of TGP in terms of its effect on lipid profiles should be further confirmed.