Regulatory T cells enhance Th17 migration in psoriatic arthritis which is reversed by anti-TNF.

Regulatory T cells (Treg) prevent the migration of effector T cells toward sites of inflammation, thereby limiting disease progression. We investigated this aspect of Treg function using psoriatic arthritis (PsA) as an exemplar of chronic inflammation. Patients with PsA had an increased Th17:Treg ratio which was reversed by anti-tumor necrosis factor (TNF) therapy. Utilizing an in vitro migration assay, Treg from patients with PsA treated with conventional therapy paradoxically boosted CCR6+ effector T-cell (a surrogate for Th17) migration toward CCL20. In contrast, Treg from patients with PsA treated with anti-TNF suppressed CCL20-driven effector T-cell migration. The boosting effect of TNF blockade upon Treg suppression of migration was accompanied by increased effector T-cell CCL20 production and enhanced interaction between Treg and effector T cells. This study provides mechanistic insight into Treg modulation of effector T-cell migration in patients with chronic inflammation and how this can be targeted by therapy.

Early treatment with rituximab in newly diagnosed systemic lupus erythematosus patients: a steroid-sparing regimen.

OBJECTIVES: To assess the effectiveness of B-cell depletion therapy (BCDT) as a steroid-sparing treatment in newly diagnosed SLE patients. METHODS: Eight female SLE patients were treated with BCDT using a rituximab/CYC-based regimen aiming to avoid the routine use of oral steroids. Post-treatment, patients were given AZA. The BILAG disease activity index was used for clinical assessment. Serum anti-dsDNA, complement (C3), ESR, circulating B lymphocytes (CD19(+)) and protein : creatinine ratio were tested at 0, 1, 3, 6 and 12 months post-treatment. Disease activity and steroid requirement over the first 6 months of treatment were compared with three SLE patients treated conventionally, each carefully matched for ethnicity, sex, age at disease onset and disease duration at diagnosis. RESULTS: All patients achieved B-cell depletion (CD19 count <0.005 × 10(9)/l). The mean decrease in global BILAG at 6 months for the BCDT patients was -12.0 vs 13.22 for the controls. Post-BCDT, no patient developed any significant deterioration, mean ESR fell from 70.12 to 17.14 mm/h at 6 months, mean serum anti-dsDNA antibody levels fell by >70% at 1 month and serum C3 level normalized in two patients by 6 months. There were no adverse events. The mean cumulative prednisolone dose at 6 months for the BCDT patients was 1287.3 mg (range 250-4501.8 mg) vs 2834.6 mg (range 0-6802.5 mg) for the controls. CONCLUSION: Early treatment of SLE patients with BCDT is safe and effective and enables a reduction in the overall steroid burden.

Delays in recognition and management of giant cell arteritis: results from a retrospective audit.

Prompt institution of corticosteroids (CS) can prevent devastating neuro-ophthalmic complications (NOC) in patients with giant cell arteritis (GCA). Guidelines on managing GCA place emphasis on early recognition of symptoms and prompt treatment of the disease where there is a high index of clinical suspicion. The aims of this study are to review the clinical findings in patients with GCA, evaluate the baseline practice in diagnosis and treatment and to identify delays in treating patients with NOC. The study utilised retrospective case notes review of patients diagnosed with GCA between 2003 and 2008. Sixty-five patients were identified (47 females, 18 males, mean age, 75 years). A significant minority presented with constitutional, polymyalgic and ischaemic symptoms. Mean time from symptom onset to diagnosis of GCA was 35 days. CS were not delayed in those diagnosed with GCA. Recognition of ischaemic symptoms was slow. Visual loss at presentation occurred in 16 patients (24.6%). Ten patients (15.4%) presented with NOC in the absence of headache, seven (70%) of whom developed permanent visual impairment. Five (7.7%) patients had cerebrovascular complications. There are major delays in the recognition and treatment of GCA. There is a high incidence of irreversible ischaemic complications which may partly result from diagnostic and treatment delay.