IgG anti-IgA antibodies in paediatric antibody-deficient patients receiving intravenous immunoglobulin.

Background: Immunoglobulin replacement therapy is an effective route of management for both infections and non-infectious complications in predominantly antibody deficiency (PAD). Trace levels of IgA (ranged from 0.4 to 2500 mg/ml), which exist in all immunoglobulin products, could lead to an increased susceptibility for adverse reactions in PAD patients.

A cross-sectional pilot study assessing needs and attitudes to implementation of Information and Communication Technology for rational use of medicines among healthcare staff in rural Tanzania.

Background: In resource-poor countries access to essential medicines, suboptimal prescribing and use of medicines are major problems. Health workers lack updated medical information and treatment support. Information and Communication Technology (ICT) could help tackle this.

Role of TG-interacting factor (Tgif) in lipid metabolism.

TG interacting factors (Tgifs) 1 and 2 are members of the TALE (three-amino-acid loop extension) superfamily of homeodomain proteins. These two proteins bind to the same DNA sequence and share a conserved C-terminal repression domain. Mutations in TGIF1 have been linked to holoprosencephaly, which is a human genetic disease that affects craniofacial development.

Rheumatoid factor and anti-CCP do not predict progressive joint damage in patients with early rheumatoid arthritis treated with prednisolone: a randomised study.

Objective: To analyse if predictors of radiographic progression differ between patients treated with or without prednisolone in early rheumatoid arthritis (RA). Radiographs of hands and feet were assessed using the modified Sharp/van der Heijde score and radiographic progression was defined as an increase in the total Sharp score above 5.8 (the smallest detectable change).

Nesting doctoral students in collaborative North-South partnerships for health systems research.

Background: The European Union (EU) supports North-South Partnerships and collaborative research projects through its Framework Programmes and Horizon 2020. There is limited research on how such projects can be harnessed to provide a structured platform for doctoral level studies as a way of strengthening health system research capacity in sub-Saharan Africa (SSA).

Objective: The aim of this study was to explore the challenges of, and facilitating factors for, 'nesting' doctoral students in North-South collaborative research projects.

Differential role of nonhomologous end joining factors in the generation, DNA damage response, and myeloid differentiation of human induced pluripotent stem cells.

Nonhomologous end-joining (NHEJ) is a key pathway for efficient repair of DNA double-strand breaks (DSBs) and V(D)J recombination. NHEJ defects in humans cause immunodeficiency and increased cellular sensitivity to ionizing irradiation (IR) and are variably associated with growth retardation, microcephaly, and neurodevelopmental delay. Repair of DNA DSBs is important for reprogramming of somatic cells into induced pluripotent stem cells (iPSCs).

Reductions in serum levels of LDL cholesterol, apolipoprotein B, triglycerides and lipoprotein(a) in hypercholesterolaemic patients treated with the liver-selective thyroid hormone receptor agonist eprotirome.

Background: Liver-selective thyromimetic agents could provide a new approach for treating dyslipidaemia.

Methods: We performed a multicentre, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of eprotirome, a liver-selective thyroid hormone receptor agonist, in 98 patients with primary hypercholesterolaemia. After previous drug wash-out and dietary run-in, patients received 100 or 200 μg day(-1) eprotirome or placebo for 12 weeks.

Low-dose prednisolone treatment of early rheumatoid arthritis and late cardiovascular outcome and survival: 10-year follow-up of a 2-year randomised trial.

Objective: To examine the long-term effects of early low-dose prednisolone use in patients with rheumatoid arthritis (RA) on cardiovascular (CV) morbidity and mortality.

Design: Retrieval of data from a 2-year open randomised trial comparing prednisolone 7.5 mg/day in addition to disease-modifying antirheumatic drugs (DMARDs) with DMARD therapy alone.

Serological assessment for celiac disease in IgA deficient adults.

Purpose: Selective immunoglobulin A deficiency is the most common primary immunodeficiency disorder that is strongly overrepresented among patients with celiac disease (CD). IgG antibodies against tissue transglutaminase (tTG) and deamidated gliadin peptides (DGP) serve as serological markers for CD in IgA deficient individuals, although the diagnostic value remains uncertain. The aim of this study was to investigate the prevalence of these markers in a large cohort of IgA deficient adults with confirmed or suspected CD and relate the findings to gluten free diet.

Guidelines for maternal and neonatal "point of care": needs of and attitudes towards a computerized clinical decision support system in rural Burkina Faso.

Background: In 2010, 245,000 women died due to pregnancy-related causes in sub-Saharan Africa and southern Asia. Our study is nested into the QUALMAT project and seeks to improve the quality of maternal care services through the introduction of a computerized clinical decision support system (CDSS) to help healthcare workers in rural areas. Healthcare information technology applications in low-income countries may improve healthcare provision but recent studies demonstrate unintended consequences with underuse or resistance to CDSS and that the fit between the system and the clinical needs does present challenges.

TG-interacting factor 1 acts as a transcriptional repressor of sterol O-acyltransferase 2.

Acat2 [gene name: sterol O-acyltransferase 2 (SOAT2)] esterifies cholesterol in enterocytes and hepatocytes. This study aims to identify repressor elements in the human SOAT2 promoter and evaluate their in vivo relevance. We identified TG-interacting factor 1 (Tgif1) to function as an important repressor of SOAT2.

Caucasian origin of disease associated HLA haplotypes in chinese blood donors with IgA deficiency.

Purpose: Selective immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in Caucasians with a prevalence of 1:600. However, the prevalence of IgAD is markedly lower in East Asian countries but no genetic studies have been performed on IgAD individuals in the Mongoloid population.

Methods: We investigated the prevalence of IgAD in a large number of Chinese blood donors (n = 39,015) in Shanghai, China.

Environmental and genetic factors in the development of anticitrullinated protein antibodies (ACPAs) and ACPA-positive rheumatoid arthritis: an epidemiological investigation in twins.

Objective: To investigate the role of genetic and environmental factors in the development of anticitrullinated protein antibodies (ACPA) and ACPA-positive rheumatoid arthritis (RA) in a twin cohort.

Methods: A total of 12 590 twins were analysed for the presence of ACPAs (CCP2 ELISA), HLA-DRB1 shared epitope (SE) gene alleles, and exposure to smoking. Twins with established RA were identified in national public care registers.

IgA subclass switch recombination in human mucosal and systemic immune compartments.

Human immunoglobulin A (IgA) comprises two IgA subclasses, IgA1 and IgA2, whose distribution has been shown by immunohistochemistry to be different in various body compartments. In comparison with systemic immune compartments, we investigated the IgA switch profiles at the molecular level in salivary and lacrimal glands, nasal mucosa, and proximal and distal gut mucosa. Direct switching from IgM to IgA1 or IgA2 predominated in all immune compartments analyzed.

New facets of antibody deficiencies.

Antibody deficiencies are the most prevalent forms of primary immunodeficiencies (PIDs). Several disease-causing mutations have been identified to date, but still, the genetic background of most patients remains elusive. During the last 2 years, next generation sequencing has revealed the genetic basis for a number of these disorders.

Influence of growth hormone on circulating fibroblast growth factor 21 levels in humans.

Objective: Findings from animal studies indicate that growth hormone (GH) may stimulate the production of the putative metabolic regulator fibroblast growth factor 21 (FGF21). We investigated whether circulating FGF21 levels are altered in patients with GH deficiency and characterized how levels of this growth factor are influenced by acute and long-term administration of GH, and the potential relationship between FGF21 and nonesterified fatty acids (NEFAs).

Design And Setting: GH-deficient patients (n = 9) were studied prior to and during 1 year of replacement with GH.

Cerebrotendinous xanthomatosis.

Purpose Of Review: Cerebrotendinous xanthomatosis (CTX) is a rare neurological disease characterized by accumulation of cholesterol and cholestanol in brain and tendons caused by a mutation in the sterol 27-hydroxylase gene (CYP27A1). The mechanism behind the accumulation of cholestanol in the brain was recently clarified and a role of 27-hydroxycholesterol as a regulator of brain cholesterol homeostasis has been established.

Recent Findings: There is a significant flux of the bile acid precursor 7α-hydroxy-4-cholesten-3-one across the blood-brain barrier in cy27-/- mice with its subsequent conversion into cholestanol.

Therapeutic DNA vaccination using in vivo electroporation followed by standard of care therapy in patients with genotype 1 chronic hepatitis C.

Clearance of infections caused by the hepatitis C virus (HCV) correlates with HCV-specific T cell function. We therefore evaluated therapeutic vaccination in 12 patients with chronic HCV infection. Eight patients also underwent a subsequent standard-of-care (SOC) therapy with pegylated interferon (IFN) and ribavirin.

Relation of activation-induced deaminase (AID) expression with antibody response to A(H1N1)pdm09 vaccination in HIV-1 infected patients.

The relevance of CD4+T-cells, viral load and age in the immunological response to influenza infection and vaccination in HIV-1 infected individuals has previously been pointed out. Our study aimed at assessing, in the setting of 2009 A(H1N1)pdm09 influenza vaccination, whether quantification of activation-induced deaminase (AID) expression in blood B-cells may provide additional indications for predicting antibody response to vaccination in HIV-1 infected patients with similar CD4+T-cell counts and age. Forty-seven healthy controls, 37 ART-treated and 17 treatment-naïve HIV-1 infected patients were enrolled in the study.

Non-structural 3 protein expression is associated with T cell protein tyrosine phosphatase and viral RNA levels in chronic hepatitis C patients.

The hepatitis C virus (HCV) non-structural 3 (NS3) protein plays key roles in both the viral life cycle and in the modulation of intrahepatic signaling and immunity. We recently showed that NS3 cleaves the T cell protein tyrosine phosphatase (TCPTP). To better understand the inactivation of TCPTP in HCV-infected humans, we investigated whether there is an association between TCPTP cleavage, NS3 protein levels and clinical parameters in hepatitis C patients.

IgA deficiency: what is new?

Purpose Of Review: To summarize recent publications on clinical and genetic aspects of IgA deficiency (IgAD).

Recent Findings: Both major histocompatibility complex (MHC) and non-MHC genes contribute to susceptibility to the disease. The former genes appear to be located in different parts of the MHC region depending on the HLA haplotype.

Diet and fatty acid pattern among patients with SLE: associations with disease activity, blood lipids and atherosclerosis.

Objective: As atherosclerosis is increased in systemic lupus erythematosus (SLE) we compared dietary habits in patients with SLE with controls, and in the patients studied associations of diet components, especially fatty acids (FAs), with disease activity, serum lipids and carotid plaque presence.

Methods: In all 114 patients with SLE and 122 age- and sex-matched population-based controls answered a food frequency questionnaire (FFQ). Subcutaneous abdominal fat cell aspiration was analysed as to FA content and plaque occurrence was determined by B-mode ultrasound.

Placental transfer of maternally-derived IgA precludes the use of guthrie card eluates as a screening tool for primary immunodeficiency diseases.

There is a need for neonatal screening tools to improve the long-term clinical outcome of patients with primary immunodeficiency diseases (PID). Recently, a PCR-based screening method for both TRECs and KRECs using Guthrie card samples has been developed. However, the applicability of these excision circle assays is limited to patients with severe T or B cell lymphopenia (SCID, XLA and A-T), whereas the most common forms of PID are not detected.