Samantha Moore

Compromised Function of Regulatory T Cells in Rheumatoid Arthritis and Reversal by Anti-TNFα Therapy

Regulatory T cells have been clearly implicated in the control of disease in murine models of autoimmunity. The paucity of data regarding the role of these lymphocytes in human autoimmune disease has prompted us to examine their function in patients with rheumatoid arthritis (RA). Regulatory (CD4+CD25+) T cells isolated from patients with active RA displayed an anergic phenotype upon stimulation with anti-CD3 and anti-CD28 antibodies, and suppressed the proliferation of effector T cells in vitro. However, they were unable to suppress proinflammatory cytokine secretion from activated T cells and monocytes, or to convey a suppressive phenotype to effector CD4+CD25− T cells. Treatment with antitumor necrosis factor α (TNFα; Infliximab) restored the capacity of regulatory T cells to inhibit cytokine production and to convey a suppressive phenotype to “conventional” T cells. Furthermore, anti-TNFα treatment led to a significant rise in the number of peripheral blood regulatory T cells in RA patients responding to this treatment, which correlated with a reduction in C reactive protein. These data are the first to demonstrate that regulatory T cells are functionally compromised in RA, and indicate that modulation of regulatory T cells by anti-TNFα therapy may be a further mechanism by which this disease is ameliorated.

Tuberculosis and anti-TNF treatment: experience of a central London hospital

Reactivation of latent tuberculosis (TB) is an established risk of anti-tumour necrosis factor α (anti-TNF) therapy. We report five cases of active TB occurring in 703 patients treated with anti-TNF therapy over a 10-year period in a central London hospital and review our screening practices for identifying latent TB prior to anti-TNF treatment. Four patients were receiving adalimumab and one patient etanercept at the time of TB diagnosis. Four of the five patients were born in countries with a high TB prevalence. Two of the five patients were healthcare workers. All patients had normal chest radiographs prior to anti-TNF treatment. Our data emphasise that country of origin is important in the determining risk of latent TB and that a normal chest radiograph does not exclude latent TB.

A patient-initiated DMARD self-monitoring service for people with rheumatoid or psoriatic arthritis on methotrexate: a randomised controlled trial

Objective To determine the effectiveness of a patient-initiated disease-modifying antirheumatic drugs (DMARD) self-monitoring service for people with rheumatoid (RA) or psoriatic arthritis (PsA) on methotrexate. Methods A two-arm, single-centre, randomised controlled trial assessing superiority in relation to healthcare use, clinical and psychosocial outcomes. Participants were 100 adults with either RA or PsA on a stable dose of methotrexate, randomly assigned to usual care or the patient-initiated service. Intervention participants were trained how to understand and interpret their blood tests and use this information to initiate care from their clinical nurse specialist (CNS). The primary outcome was the number of outpatient visits to the CNS during the trial period. Differences between groups were analysed using Poisson regression models. Secondary outcomes were collected at baseline and after the third and sixth blood tests. Disease activity was measured using either the Disease Activity Score in 28 joints or Psoriatic Arthritis Response Criteria (PsARC), pain and fatigue using a visual numeric scale and the Health Assessment Question-II, Hospital Anxiety and Depression Scale and SF12 were completed to assess disability, mood and quality of life, respectively. Differences between groups over time on secondary outcomes were analysed using multilevel models. Results The patient-initiated DMARD self-monitoring service was associated with 54.55% fewer visits to the CNS (p<0.0001), 6.80% fewer visits to the rheumatologist (p=0.23) and 38.80% fewer visits to the general practitioner (p=0.07), compared with control participants. There was no association between trial arm and any of the clinical or psychosocial outcomes. Conclusions The results suggest that a patient-initiated service that incorporates patients’ self-monitoring DMARD therapy can lead to significant reductions in healthcare use, while maintaining clinical and psychosocial well-being. Trial registration number ISRCTN21613721.