Spontaneous operational tolerance to the allograft develops in a proportion of liver transplantation (LT) recipients weaned off immunosuppressive (IS) drugs. Several studies have investigated... Show moreSpontaneous operational tolerance to the allograft develops in a proportion of liver transplantation (LT) recipients weaned off immunosuppressive (IS) drugs. Several studies have investigated whether peripheral blood circulating T cells could play a role in the development or identify operational tolerance, but never characterized alloreactive T cells in detail due to the lack of a marker for these T cells. In this study, we comprehensively investigated phenotypic and functional characteristics of alloreactive circulating T cell subsets in tolerant LT recipients (n = 15) using multiparameter flow cytometry and compared these with LT recipients on IS drugs (n = 23) and healthy individuals (n = 16). Activation-induced CD137 was used as a marker for alloreactive T cells upon allogenic stimulation. We found that central and effector memory CD4+ T cells were hyporesponsive against donor and third-party splenocyte stimulation in tolerant LT recipients, whereas an overall hyperresponsiveness was observed in alloreactive terminally differentiated effector memory CD4+ T cells. In addition, elevated percentages of circulating activated T helper cells were observed in these recipients. Lastly, tolerant and control LT recipients did not differ in donor-specific antibody formation. In conclusion, a combination of circulating hyperresponsive highly differentiated alloreactive CD4+ T cells and circulating activated T helper cells could discriminate tolerant recipients from a larger group of LT recipients. Show less
Objective To investigate the association between baseline serum adipokines levels-leptin, adiponectin and resistin-and long-term progression of hand osteoarthritis (HOA). Methods Baseline and 6... Show moreObjective To investigate the association between baseline serum adipokines levels-leptin, adiponectin and resistin-and long-term progression of hand osteoarthritis (HOA). Methods Baseline and 6-year radiographs of 164 patients (mean age 60 years, 81% women) with HOA (defined as a Kellgren and Lawrence score >= 2 in at least two hand joints) were assessed for joint space narrowing (JSN) in 32 hand joints using the Osteoarthritis Research Society International atlas. Progression was defined as a change in the sum of the JSN score above the smallest detectable change of 2, reflecting change above measurement error. Serum adipokines were measured at baseline and patients were categorised by adipokine tertiles. RRs (and 95% CI) of HOA progression for patients in the second and third tertiles were calculated relative to the first tertile, using generalised estimating equations. Adjustments were made for age, sex and body mass index. Results Patients in the two highest tertiles of adiponectin had a decreased risk of 70% (RR = 0.3 (0.2 to 0.7)) for HOA progression in comparison with patients in the lowest tertile. Leptin and resistin levels were not associated with progression. Conclusion Adiponectin levels are associated with progression of HOA, suggesting that adiponectin may be involved in the pathophysiology of OA. Show less
