The phenotype of circulating follicular-helper T cells in patients with rheumatoid arthritis defines CD200 as a potential therapeutic target

Rheumatoid arthritis (RA) is a systemic autoimmune disease primarily affecting synovial joints in which the development of autoantibodies represents a failure of normal tolerance mechanisms, suggesting a role for follicular helper T cells (TFH) in the genesis of autoimmunity. To determine whether quantitative or qualitative abnormalities in the circulating TFH cell population exist, we analysed by flow cytometry the number and profile of these cells in 35 patients with RA and 15 matched controls. Results were correlated with patient characteristics, including the presence of autoantibodies, disease activity, and treatment with biologic agents. Circulating TFH cells from patients with RA show significantly increased expression of the immunoglobulin superfamily receptor CD200, with highest levels seen in seropositive patients (P=0.0045) and patients treated with anti-TNFα agents (P=0.0008). This occurs in the absence of any change in TFH numbers or overt bias towards Th1, Th2, or Th17 phenotypes. CD200 levels did not correlate with DAS28 scores (P=0.887). Although the number of circulating TFH cells is not altered in the blood of patients with RA, the TFH cells have a distinct phenotype. These differences associate TFH cells with the pathogenesis of RA and support the relevance of the CD200/CD200R signalling pathway as a potential therapeutic target

A whole blood monokine-based reporter assay provides a sensitive and robust measurement of the antigen-specific T cell response

<p>Abstract</p> <p>Background</p> <p>The ability to measure T-cell responses to antigens is proving critical in the field of vaccine development and for understanding immunity to pathogens, allergens and self-antigens. Although a variety of technologies exist for this purpose IFNγ-ELISpot assays are widely used because of their sensitivity and simplicity. However, ELISpot assays cannot be performed on whole blood, and require relatively large volumes of blood to yield sufficient numbers of peripheral blood mononuclear cells. To address these deficiencies, we describe an assay that measures antigen-specific T cell responses through changes in monokine gene transcription. The biological amplification of the IFNγ signal generated by this assay provides sensitivity comparable to ELISpot, but with the advantage that responses can be quantified using small volumes of whole blood.</p> <p>Methods</p> <p>Whole blood or peripheral blood mononuclear cells (PBMCs) from healthy controls and immunosuppressed recipients of solid organ transplants were incubated with peptide pools covering viral and control antigens or mitogen for 20 hours. Total RNA was extracted and reverse transcribed before amplification in a TaqMan qPCR reaction using primers and probes specific for MIG (CXCL9), IP-10 (CXCL10) and HPRT. The induction of MIG and IP-10 in response to stimuli was analysed and the results were compared with those obtained by ELISpot.</p> <p>Results</p> <p>Antigen-specific T cell responses can be measured through the induction of MIG or IP-10 gene expression in PBMCs or whole blood with results comparable to those achieved in ELISpot assays. The biological amplification generated by IFNγ-R signaling allows responses to be detected in as little as 25 μL of whole blood and enables the assay to retain sensitivity despite storage of samples for up to 48 hours prior to processing.</p> <p>Conclusions</p> <p>A monokine-based reporter assay provides a sensitive measure of antigen-specific T cell activation. Assays can be performed on small volumes of whole blood and remain accurate despite delays in processing. This assay may be a useful tool for studying T cell responses, particularly when samples are limited in quantity or when storage or transportation is required before processing.</p

Treatment for primary hypothyroidism: current approaches and future possibilities

Primary hypothyroidism is the most common endocrine disease. Although the diagnosis and treatment of hypothyroidism is often considered simple, there are large numbers of people with this condition who are suboptimally treated. Even in those people with hypothyroidism who are biochemically euthyroid on levothyroxine replacement there is a significant proportion who report poorer quality of life. This review explores the historical and current treatment options for hypothyroidism, reasons for and potential solutions to suboptimal treatment, and future possibilities in the treatment of hypothyroidism

With a little help from my friends: Developing an assisted automated peritoneal dialysis program in Western Australia

Background: Nurse-assisted automated peritoneal dialysis (AAPD) offers a model of care that has been successfully used in frail dialysis populations internationally. AAPD offers cost savings over hospitalisation on peritoneal dialysis (PD) or in-centre haemodialysis (HD). Method: A pilot AAPD model of care was developed in Western Australia (WA). Patient evaluation was measured utilising a perceptions of dialysis survey, clinical events, hospitalisation and peritonitis rates, Charlson Comorbidity Index (CCI), KDQoL-SF 36 and a survey. Staff opinions and perceived competency were measured by an online survey. Economic analysis was undertaken. Results: A successful collaborative model was developed. 40 staff were trained and competency significantly improved during program delivery (p &lt; 0.0001). 15 patients with an average CCI score of 8.7 used the service for 18 periods of care over 18 months (mean 33 days SD 47). Two non-renal cause deaths and two episodes of peritonitis occurred. Patient opinions were extremely positive. Cost savings were estimated at $620,000. Conclusion: In WA, an AAPD pilot program has been successfully developed and delivered. A sustainable model has overcome initial hurdles. Staff have gained new skills and delivered effective care, demonstrated by high patient acceptance. The program was cost-effective compared to staying in hospital or transferring to HD

Cross-sectional and longitudinal studies suggest pharmacological treatment used in patients with glucokinase mutations does not alter glycaemia

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.Heterozygous glucokinase (GCK) mutations cause mild, fasting hyperglycaemia from birth. Although patients are usually asymptomatic and have glycaemia within target ranges, some are put on pharmacological treatment. We aimed to investigate how many patients are on pharmacological treatment and the impact of treatment on glycaemic control.European Community’s Seventh Framework ProgrammeNIHR Exeter Clinical Research FacilityWellcome Trus