Toll-like receptors, immunoproteasome and regulatory T cells in children with Henoch-Schönlein purpura and primary IgA nephropathy.

BACKGROUND: Henoch-Schönlein purpura (HSP) nephritis and primary IgA nephropathy (pIgAN) present with glomerular IgA deposits, but differ with regard to clinical features. The suspected involvement of different immune system pathways is largely unknown. METHODS: This study was aimed at investigating some of the immunological features including Toll-like receptors (TLR), proteasome (PS)/immunoproteasome (iPS) switch, and the regulatory T cell system (Treg/Th17 cells) in 63 children with HSP with/without renal involvement and in 25 with pIgAN. Real-time PRC (Taqman) was used to quantify mRNA levels in peripheral blood mononuclear cells (PBMC). RESULTS: The expression of mRNAs encoding for TLR4 in both HSP and pIgAN was higher than in controls (HC) and in both diseases FoxP3mRNA and TGF-ß1mRNA expression was significantly lower than in HC. A switch from PS to iPS (LMP2/ß1) was detected only in PBMC of HSP and it correlated with the level of TLR2mRNA, which was selectively increased only in children with HSP. CONCLUSION: Children with HSP and pIgAN present with similar signs of engagement of the innate immunity and regulatory T cell depression. The increased immunoproteasome switch, which correlated with TLR2 activation, may suggest an innate immunity pathway peculiar to HSP vasculitic presentation. This research area also deserves further investigation for possible therapeutic applications.

Drug use and upper gastrointestinal complications in children: a case-control study.

OBJECTIVE: To evaluate the risk of upper gastrointestinal complications (UGIC) associated with drug use in the paediatric population. METHODS: This study is part of a large Italian prospective multicentre study. The study population included children hospitalised for acute conditions through the emergency departments of eight clinical centres. Patients admitted for UGIC (defined as endoscopically confirmed gastroduodenal lesions or clinically defined haematemesis or melena) comprised the case series; children hospitalised for neurological disorders formed the control group. Information on drug and vaccine exposure was collected through parental interview during the children's hospitalisation. Logistic regression was used to estimate ORs for the occurrence of UGIC associated with drug use adjusted for age, clinical centre and concomitant use of any drug. RESULTS: 486 children hospitalised for UGIC and 1930 for neurological disorders were enrolled between November 1999 and November 2010. Drug use was higher in cases than in controls (73% vs 54%; p<0.001). UGICs were associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) (adjusted OR 2.9, 95% CI 2.1 to 4.0), oral steroids (adjusted OR 2.9, 95% CI 1.7 to 4.8) and antibiotics (adjusted OR 2.3, 95% CI 1.8 to 3.1). The duration of use of these drug categories was short (range 1-8 days). Paracetamol showed a lower risk (adjusted OR 2.0, 95% CI 1.5 to 2.6) compared to ibuprofen (adjusted OR 3.7, 95% CI 2.3 to 5.9), although with partially overlapping CIs. CONCLUSIONS: NSAIDs, oral steroids and antibiotics, even when administered for a short period, were associated with an increased risk of UGIC.

Community-acquired bloodstream infections among paediatric patients admitted to an Italian tertiary referral centre: a prospective survey.

Introduction. Invasive bacterial diseases continue to represent a significant burden in paediatric age, and the emergence of previously secondary bacteria and antibiotic-resistant strains requires a continuous surveillance. Materials and methods. A one-year prospective survey on laboratory confirmed community-acquired bloodstream infections (CA-LBSIs) cases admitted to an Italian tertiary specialistic paediatric Hospital. Results. Twelve cases were documented, with an incidence rate of 0.39/1,000 admissions to the Emergency Department, and of 2.9/1,000 hospitalizations to general and specialized wards. Mean age at diagnosis was 5.2 +/- 5.9 years, with 58.3% of episodes regarding children younger than years. Six episodes were caused by Gram positive and six by Gram negative bacteria, with potential vaccine-preventable pathogens responsible of 50% of CA-LBSIs. Empiric antibiotic therapy prescribed at admission was found appropriate to microbiological results in the totality of cases and administered for a mean time of 17.7 +/- 10.1 days. No resistant strains were found. All patients had a good outcome. Conclusions. Prompt collection of samples for microbiological tests together with the rapid institution of empiric antibiotic therapy are essential for the correct management of CA-LBSIs in paediatric patients. Implementation of vaccinations against the major responsible pathogens remains the most important prevention strategy.