The clinical spectrum of de novo donor-specific antibodies in pediatric renal transplant recipients.

The development of donor-specific HLA antibodies (DSA) is associated with worse renal allograft survival in adult patients. This study assessed the natural history of de novo DSA, and its impact on renal function in pediatric renal transplant recipients (RTR). HLA antibodies were measured prospectively using single-antigen-bead assays at 1, 3, 6 and 12 months posttransplant followed by 12-monthly intervals and during episodes of allograft dysfunction. Of 215 patients with HLA antibody monitoring, 75 (35%) developed DSA at median of 0.25 years posttransplant with a high prevalence of Class II (70%) and HLA-DQ (45%) DSA. DSA resolved in 35 (47%) patients and was associated with earlier detection (median, inter-quartile range 0.14, 0.09-0.33 vs. 0.84, 0.15-2.37 years) and lower mean fluorescence intensity (MFI) (2658, 1573-3819 vs. 7820, 5166-11 990). Overall, DSA positive patients had more rapid GFR decline with a 50% reduction in GFR at mean 5.3 (CI: 4.7-5.8) years versus 6.1 (5.7-6.4) years in DSA negative patients (p = 0.02). GFR decreased by a magnitude of 1 mL/min/1.73 m(2) per log10 increase in Class II DSA MFI (p < 0.01). Using Cox regression, independent factors predicting poorer renal allograft outcome were older age at transplant (hazard ratio 1.1, CI: 1.0-1.2 per year), tubulitis (1.5, 1.3-1.8) and microvasculature injury (2.9, 1.4-5.7). In conclusion, pediatric RTR with de novo DSA and microvasculature injury were at risk of allograft failure.

The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniae bacteraemia and predicts mortality.

This multicentre prospective study was conducted to investigate whether the level of the soluble form of urokinase-type plasminogen activator receptor (suPAR) is elevated during pneumococcal bacteraemia and is of predictive value in the early stage of the disease. Plasma levels of suPAR were increased significantly (median 5.5; range 2.4-21.0 ng/mL) in 141 patients with pneumococcal bacteraemia, compared to 31 healthy controls (median 2.6, range 1.5-4.0 ng/mL, p 0.001). Furthermore, suPAR levels were elevated significantly in patients who died from the infection (n = 24) compared to survivors (n = 117; p < 0.001). No correlation was found between suPAR levels and C-reactive protein. In univariate logistic regression analysis, hypotension, renal failure, cerebral symptoms and high serum concentrations of protein YKL-40 and suPAR were associated significantly with mortality (p < 0.05). In multivariate analysis, only suPAR remained a significant predictor of death (mortality rate of 13 for suPAR levels of > 10 ng/mL; 95% CI: 1.1-158). The increase in suPAR levels may reflect increased expression by vascular or inflammatory cells in the setting of pneumococcal sepsis. This plasma protein may be used to identify patients who are severely ill with pneumococcal bacteraemia.

[Molecular effects of vitamin D on cell cycle and oncogenesis]. / Vitamin D's molekylaere effekt på cellecyklus og onkogenese.

The active metabolite of vitamin D, 1,25 (OH)2D3, exerts its cell cycle regulating effects via binding to VDR (Vitamin D Receptor). This complex forms a heterodimer with RXR (Retinoic X Receptor). The VDR-RXR heterodimer binds to promoter regions of cell cycle regulating genes through a vitamin D response element (VDRE). The tumour suppressor gene cyclin kinase inhibitor (Cki) p21, one of the well known cell cycle regulating genes, is one of the genes regulated in this manner. Its tumour suppressive action is through inhibition of cell division. These molecular biological mechanisms and large epidemiological investigations give strong support for the benefits of vitamin D in preventing colon cancer and prostate cancer.

Chemokine receptor CCR5 in interferon-treated multiple sclerosis.

OBJECTIVE: To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta). METHODS: The CCR5 Delta32 allele and a CCR5 promoter polymorphism associated with cell surface expression of CCR5 were analyzed in 109 patients with relapsing-remitting MS treated with IFN-beta who were followed clinically for 1 year. Cellular CCR5 expression was measured by flow cytometry. RESULTS: Patients with MS had a higher percentage of CCR5-positive monocytes than healthy controls. Increased monocyte expression of CCR5 correlated weakly with an increased short-term relapse risk but there was no relationship between CCR5 Delta32 allele and CCR5 promoter polymorphism genotypes and relapse risk. CONCLUSIONS: The results do not support a major role of CCR5 in the pathogenesis of relapses in MS patients treated with IFN-beta, but it is possible that monocyte CCR5 expression may be used as a marker of disease activity.