Spleen stiffness measurement by transient elastography to diagnose portal hypertension in children.

Background: The development of esophageal varices is a late complication of chronic liver disease (LD) in children. The diagnosis is presently limited to invasive procedures such as endoscopy. Noninvasive tools to diagnose the presence and degree of esophageal varices would alter management decisions and support indications for invasive procedures in affected children.

Clinical picture and treatment of 2212 patients with common variable immunodeficiency.

Background: Common variable immunodeficiency (CVID) is an antibody deficiency with an equal sex distribution and a high variability in clinical presentation. The main features include respiratory tract infections and their associated complications, enteropathy, autoimmunity, and lymphoproliferative disorders.

Objective: This study analyzes the clinical presentation, association between clinical features, and differences and effects of immunoglobulin treatment in Europe.

Structural characterization of the ribonuclease H-like type ASKHA superfamily kinase MK0840 from Methanopyrus kandleri.

Murein recycling is a process in which microorganisms recover peptidoglycan-degradation products in order to utilize them in cell wall biosynthesis or basic metabolic pathways. Methanogens such as Methanopyrus kandleri contain pseudomurein, which differs from bacterial murein in its composition and branching. Here, four crystal structures of the putative sugar kinase MK0840 from M.

High-content cytometry and transcriptomic biomarker profiling of human B-cell activation.

Background: Primary antibody deficiencies represent the most prevalent, although very heterogeneous, group of inborn immunodeficiencies, with a puzzling complexity of cellular and molecular processes involved in disease pathogenesis.

Objective: We aimed to study in detail the kinetics of CD40 ligand/IL-21-induced B-cell differentiation to define new biomarker sets for further research into primary antibody deficiencies.

Methods: We applied high-content screening methods to monitor B-cell activation on the cellular (chip cytometry) and transcriptomic (RNA microarray) levels.

Vitamin D deficiency and insufficiency after pediatric liver transplantation.

Vitamin D deficiency and insufficiency are increasingly recognized in the general population, including healthy children. There is also an increasing emphasis on the importance of vitamin D status following pediatric liver transplantation and specifically its relationship to metabolic bone disease and growth retardation. Vitamin D insufficiency has also been associated with multiple immunological and metabolic disorders in adults.

Home monitoring and decision support for international liver transplant children.

Complications may occur after a liver transplantation, therefore proper monitoring and care in the post-operation phase plays a very important role. Sometimes, monitoring and care for patients from abroad is difficult due to a variety of reasons, e.g.

The use of transient elastography and non-invasive serum markers of fibrosis in pediatric liver transplant recipients.

The use of non-invasive markers to diagnose liver allograft fibrosis is not well established in children after LTx. TE, FT, and ELF score were performed in 117 liver-transplanted children (60M, 8.9 [0.

Autophagy-enhancing drug carbamazepine diminishes hepatocellular death in fibrinogen storage disease.

Fibrinogen storage disease (FSD) is a rare autosomal-dominant hereditary disorder characterized by hypofibrinogenemia and accumulation of fibrinogen aggregates within the hepatocellular endoplasmatic reticulum (ER). Some FSD patients present with elevated amino-transferases and fibrosis/cirrhosis similar to alpha-1-antitrypsin deficiency (ATD), also an ER storage disease. Pharmacological stimulation of autophagy has been shown to mediate clearance of protein aggregates and halt progression of liver fibrosis in in vivo models of ATD.

Results of single-center screening for chronic hepatitis E in children after liver transplantation and report on successful treatment with ribavirin.

RNA screening for HEV in 22 liver-transplanted children with chronic graft hepatitis out of a cohort of 267 liver-transplanted children detected a single patient with chronic HEV infection. Although this patient remained viremic for 33 months, anti-HEV-IgG was not detectable with MP assay but with Wantai assay. We present the first case of successful ribavirin therapy in an immunosuppressed child with chronic HEV infection.

Application and limitations of transient liver elastography in children.

Objectives: Transient elastography (TE) using the FibroScan has gained popularity recently for the noninvasive diagnosis of hepatic fibrosis. Data on its use in children younger than 6 years are still scarce, and the influence of technical aspects such as probe choice and site of measurement on FibroScan results is not clear. Our study aims to clarify some technical issues concerning the use of the FibroScan in children and to deliver normal FibroScan values for reference.

Loss-of-function mutations in the IL-21 receptor gene cause a primary immunodeficiency syndrome.

Primary immunodeficiencies (PIDs) represent exquisite models for studying mechanisms of human host defense. In this study, we report on two unrelated kindreds, with two patients each, who had cryptosporidial infections associated with chronic cholangitis and liver disease. Using exome and candidate gene sequencing, we identified two distinct homozygous loss-of-function mutations in the interleukin-21 receptor gene (IL21R; c.

Heterogeneity of fibrosis patterns in non-alcoholic fatty liver disease supports the presence of multiple fibrogenic pathways.

Background: Adult non-alcoholic fatty liver disease (NAFLD) involves lobular necroinflammatory activity and fibrosis is typically centrilobular, whereas paediatric NAFLD has predominantly portal fibrosis. The reasons for these differences are unclear. We aimed to determine (a) how centrilobular and portal fibrosis in children relate to histological parameters; and (b) whether atypical fibrosis patterns exist in adults that are unexplained by current fibrogenesis models.

Mutation detection in cholestatic patients using microarray resequencing of ATP8B1 and ABCB11.

Background : Neonatal cholestasis is a common presentation of childhood liver diseases and can be a feature of various conditions including disorders of bile acid biogenesis and transport, various inborn errors of metabolism and perinatal infections. Some inherited metabolic diseases can be easily screened using biochemical assays, however many can only be accurately diagnosed by DNA sequencing. Fluorescent capillary Sanger sequencing (FS) is the gold standard method used by clinical laboratories for genetic diagnosis of many inherited conditions; however, it does have limitations.

EBV-specific T-cell immunity in pediatric solid organ graft recipients with posttransplantation lymphoproliferative disease.

Background: Posttransplantation lymphoproliferative disease (PTLD) is an often Epstein-Barr virus (EBV)-associated mainly malignant complication after transplantation. We present data on EBV-specific T cells in children treated with rituximab with or without chemotherapy on the pediatric PTLD Pilot 2005 protocol.

Methods: Peripheral blood mononuclear cells were isolated from 16 pediatric patients with PTLD, 4 transplanted children with EBV reactivation, and 18 healthy controls.

Characteristics of early and late PTLD development in pediatric solid organ transplant recipients.

Background: Posttransplantation lymphoproliferative disorders (PTLD) present a major cause of mortality and morbidity after solid organ transplantation. The purpose of this study was to identify the factors associated with the development of early- and late-onset PTLD in pediatric solid organ transplant recipients.

Methods: We examined the medical history, laboratory parameters, and pathology of 127 children with PTLD who were registered in the German multicenter pediatric PTLD registry.

Kinetics of IgM and IgA antibody response to 23-valent pneumococcal polysaccharide vaccination in healthy subjects.

Purpose: A poor antibody response of IgM and IgA antibodies upon vaccination with pneumococcal polysaccharides (PnPS) is discussed as independent risk factors for bronchiectasis in patients with antibody deficiency syndrome (ADS) receiving immunoglobulin replacement therapy. However, the kinetics of the specific IgM and IgA response to vaccination with multivalent pneumococcal polysaccharides requires a more detailed knowledge. In this study we aimed i) to develop a standardised multivalent PnPS-IgM and IgA-ELISA, and ii) to compare the sensitivity of the multivalent to the serotype specific antibody response, and iii) to determine the kinetics of the anti-PnPS IgM and IgA antibodies in healthy subjects.

Treatment of neurological autoimmune diseases with immunoglobulins: first insights from the prospective SIGNS registry.

Purpose: Several immunoglobulin (IG) preparations have been approved for the immunomodulatory treatment of the neurological autoimmune diseases (AID) Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and multifocal motor neuropathy (MMN). Although efficacy has been proven in randomised clinical trials, long-term outcome data on drug utilization, effectiveness, tolerability, health related quality of life, and economic variables are lacking.

Methods: In the prospective, observational internet-based SIGNS registry, patients of all age groups are eligible if they have received or are scheduled for IG therapy for neurological AID or primary or severe secondary immunodeficiency.

Crystal structures of archaemetzincin reveal a moldable substrate-binding site.

Background: Archaemetzincins are metalloproteases occurring in archaea and some mammalia. They are distinct from all the other metzincins by their extended active site consensus sequence HEXXHXXGXXHCX(4)CXMX(17)CXXC featuring four conserved cysteine residues. Very little is known about their biological importance and structure-function relationships.

Molecular basis for the action of the collagen-specific chaperone Hsp47/SERPINH1 and its structure-specific client recognition.

Collagen is the most abundant protein in animals and is a major component of the extracellular matrix in tissues such as skin and bone. A distinctive structural feature of all collagen types is a unique triple-helical structure formed by tandem repeats of the consensus sequence Xaa-Yaa-Gly, in which Xaa and Yaa frequently are proline and hydroxyproline, respectively. Hsp47/SERPINH1 is a procollagen-specific molecular chaperone that, unlike other chaperones, specifically recognizes the folded conformation of its client.

Naturally occurring genetic variants of human caspase-1 differ considerably in structure and the ability to activate interleukin-1β.

Caspase-1 (Interleukin-1 Converting Enzyme, ICE) is a proinflammatory enzyme that plays pivotal roles in innate immunity and many inflammatory conditions such as periodic fever syndromes and gout. Inflammation is often mediated by enzymatic activation of interleukin (IL)-1β and IL-18. We detected seven naturally occurring human CASP1 variants with different effects on protein structure, expression, and enzymatic activity.

Mucosal immunity and nasal influenza vaccination.

Influenza remains a threat to public health, with immunization being a suitable method of infection prevention and control. Our understanding of the immunological regulations at the mucosa, antigen processing and presentation, and B-cell activation has improved, enabling research and targeted induction of immune responses at the site of antigen delivery. Nasal influenza immunization has distinct features compared with intramuscular vaccines, providing protection at the pathogen's entry site, higher levels of mucosal antibodies, cross-protection and needle-free application.

Structural and biochemical characterization of native and recombinant single insulin-like growth factor-binding domain protein (SIBD-1) from the Central American hunting spider Cupiennius salei (Ctenidae).

Cupiennius salei single insulin-like growth factor binding domain protein (SIBD-1) is an 8.6 kDa Cys-, Pro-, and Gly-rich protein, discovered in the hemocytes of the Central American hunting spider Cupiennius salei. SIBD-1 exhibits high sequence similarity to the N-terminal domain of the insulin-like growth factor-binding protein superfamily and has been reported to play an important role in the spider's immune system.

Hepatic fibrosis in paediatric liver disease.

Liver fibrosis is the common endpoint of chronic liver disease of variable aetiology. Liver injury induces excess deposition of extracellular matrix via inflammatory pathways, which in turn results in distortion of the vascular liver architecture. The two features combine to cause portal hypertension and reduced hepatocellular function.

Biliary atresia.

Biliary atresia is an obliterative cholangiopathy with progressive hepatobiliary disease, starting from the perinatal period. With a frequency of 1/15-18,000 live births, biliary atresia is the commonest cause of life-threatening liver disease in infants, and fatal if untreated. Prognosis is poor, unless early diagnosis is followed by surgical treatment.