Recent animal studies have shown that CD4⁺CD25⁺ T cells play a crucial role in the suppression of the immune response and that depletion of this subset of T cells might lead to development of autoimmune diseases. The aim of the present study was to investigate the levels of CD4⁺CD25⁺ T cells in the peripheral blood of patients with systemic lupus erythematosus (SLE). Ninety‐four SLE patients, 52 patients with rheumatoid arthritis (RA) and 50 age‐ and gender‐matched healthy individuals were enrolled in the study. A flowcytometric method was applied in the measurement of CD4⁺CD25⁺ T cells. The results showed that patients with SLE had statistically lower levels of CD4⁺CD25⁺ T cells than did normal controls, when expressed as either percentages of peripheral blood mononuclear cells (PBMCs) (mean ± SD, 8.49 ± 6.36 versus 11.11 ± 4.58%, P < 0.05) or absolute cell numbers (98.77 ± 97.52 versus 213.93 ± 104.52 cells/mm³, P < 0.05). In terms of CD25^brightCD4⁺ T cells, defined as having a fluorescence intensity of CD25 expression exceeding 100, SLE patients still had significantly lower levels than did normal controls expressed as percentages of PBMCs (1.76 ± 1.32 versus 3.73 ± 1.30%, P < 0.05). No significant differences could be found between RA patients and normal controls. The overwhelming majority of CD4⁺CD25⁺ T cells belonged to CD45RO⁺ cells and most did not express the CD69 molecule. Although decreased CD4⁺CD25⁺ T cells were found in SLE patients, we failed to find a significant correlation between the levels of CD4⁺CD25⁺ T cells and disease activities of SLE. To the best of our knowledge, this is the first study to demonstrate that patients with SLE had decreased CD4⁺CD25⁺ T cells. However, the exact role of the decreased CD4⁺CD25⁺ T cells in the pathogenesis of SLE remains to be elucidated.

Objective To evaluate the use of prospective screening for the HLA-B*58:01 allele to identify Taiwanese individuals at risk of severe cutaneous adverse reactions (SCARs) induced by allopurinol treatment. Design National prospective cohort study. Setting 15 medical centres in different regions of Taiwan, from July 2009 to August 2014. Participants 2926 people who had an indication for allopurinol treatment but had not taken allopurinol previously. Participants were excluded if they had undergone a bone marrow transplant, were not of Han Chinese descent, and had a history of allopurinol induced hypersensitivity. DNA purified from 2910 participants’ peripheral blood was used to assess the presence of HLA-B*58:01. Main outcome measures Incidence of allopurinol induced SCARs with and without screening. Results Participants who tested positive for HLA-B*58:01 (19.6%, n=571) were advised to avoid allopurinol, and were referred to an alternate drug treatment or advised to continue with their prestudy treatment. Participants who tested negative (80.4%, n=2339) were given allopurinol. Participants were interviewed once a week for two months to monitor symptoms. The historical incidence of allopurinol induced SCARs, estimated by the National Health Insurance research database of Taiwan, was used for comparison. Mild, transient rash without blisters developed in 97 (3%) participants during follow-up. None of the participants was admitted to hospital owing to adverse drug reactions. SCARs did not develop in any of the participants receiving allopurinol who screened negative for HLA-B*58:01. By contrast, seven cases of SCARs were expected, based on the estimated historical incidence of allopurinol induced SCARs nationwide (0.30% per year, 95% confidence interval 0.28% to 0.31%; P=0.0026; two side one sample binomial test). Conclusions Prospective screening of the HLA-B*58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence of allopurinol induced SCARs in Taiwanese medical centres.

The paucity of lymph node T cells (plt) mutation leads to a loss of CCL21 and CCL19 expression in secondary lymphoid organs. plt mice have defects in the migration of naive T cells and activated dendritic cells into the T cell zones of lymphoid organs, suggesting that they would have defects in T cell immune responses. We now demonstrate T cell responses in plt mice are delayed but ultimately enhanced. Responses to contact sensitization are decreased at day 2 after priming but increased at day 6. After subcutaneous immunization, antigen-specific T cell proliferation and cytokine production in plt mice are increased and remain markedly elevated for at least 8 wk. Compared with wild-type mice, a proportion of T cell response in plt mice are shifted to the spleen, and prior splenectomy reduces the T cell response in draining lymph nodes. After immunization of plt mice, T cells and dendritic cells colocalize in the superficial cortex of lymph nodes and in splenic bridging channels, but not in T cell zones. These results demonstrate that plt mice mount robust T cell responses despite the failure of naive T cells and activated dendritic cells to enter the thymus dependent areas of secondary lymphoid organs.

Objective: Angiogenesis plays a part in the pathogenesis of rheumatoid arthritis (RA), and nanogold inhibits the activity of an angiogenic factor, vascular endothelial growth factor (VEGF). We therefore investigated whether intraarticular delivery of nanogold ameliorates collagen‐induced arthritis (CIA) in rats.Methods: Binding of 13‐nm nanogold to VEGF in human RA synovial fluid (SF) and its effects on RA SF–induced endothelial cell proliferation and migration were assessed. Nanogold was administered intraarticularly to rats with CIA before the onset of arthritis. Progression of CIA was monitored by measures of clinical, radiologic, and histologic changes. In addition, the microvessel density and extent of infiltrating macrophages as well as levels of tumor necrosis factor α (TNFα) and interleukin‐1β (IL‐1β) in the ankle joints were determined.Results: Nanogold bound to VEGF in RA SF, resulting in inhibition of RA SF–induced endothelial cell proliferation and migration. Significant reductions in ankle circumference, articular index scores, and radiographic scores were observed in the nanogold‐treated rats with CIA compared with their control counterparts. In addition, the histologic score (of synovial hyperplasia, cartilage erosion, and leukocyte infiltration), microvessel density, macrophage infiltration, and levels of TNFα and IL‐1β were also significantly reduced in the ankle joints of nanogold‐treated rats.Conclusion: Our results are the first to demonstrate that intraarticular administration of nanogold ameliorates the clinical course of CIA in rats. Nanogold exerted antiangiogenic activities and subsequently reduced macrophage infiltration and inflammation, which resulted in attenuation of arthritis. These results demonstrate proof of principle for the use of nanogold as a novel therapeutic agent for the treatment of RA.

Objective: MicroRNA (miRNA) plays a role in autoimmune diseases. MiRNA‐223 (miR‐223) is up‐regulated in patients with rheumatoid arthritis (RA) and is involved in osteoclastogenesis, which contributes to erosive disease. The aim of this study was to test the feasibility of using lentiviral vectors expressing the miR‐223 target sequence (miR‐223T) to suppress miR‐223 activity as a therapeutic strategy in a mouse model of collagen‐induced arthritis (CIA).Methods: Levels of miR‐223 in the synovial tissue of patients with RA or osteoarthritis (OA), as well as in the ankle joints of mice with CIA, were determined by quantitative reverse transcriptase–polymerase chain reaction (RT‐PCR). Lentiviral vectors expressing miR‐223T (LVmiR‐223T) or luciferase short hairpin RNA (LVshLuc) as a control vector were injected intraperitoneally into mice with CIA. Treatment responses and disease‐related bone mineral density were monitored. Levels of nuclear factor 1A (NF‐1A), a direct target of miR‐223, and macrophage colony‐stimulating factor receptor (M‐CSFR), which is critical for osteoclastogenesis, were measured by immunohistochemistry and quantitative RT‐PCR. Osteoclasts were assessed by tartrate‐resistant acid phosphatase staining.Results: MiR‐223 expression was significantly higher in the synovium of RA patients and in the ankle joints of mice with CIA as compared to OA patients and normal mice. LVmiR‐223T treatment reduced the arthritis score, histologic score, miR‐223 expression, osteoclastogenesis, and bone erosion in mice with CIA. Down‐regulation of miR‐223 with concomitant increases in NF‐1A levels and decreases in M‐CSFR levels was detected in the synovium of LVmiR‐223T–treated mice.Conclusion: This study is the first to demonstrate that lentivirus‐mediated silencing of miR‐223 can reduce disease severity of experimental arthritis. Furthermore, our results indicate that inhibition of miR‐223 activity should be further explored as a therapeutic strategy in RA.