Background
Vitamin D levels are known to be associated with atopic disease development; however, existing data are controversial. The aim of this study was to investigate whether corresponding ...maternal and cord blood vitamin D levels are associated with atopic outcomes in early infancy.
Methods
Within the LINA cohort study (Lifestyle and environmental factors and their Influence on Newborns Allergy risk), 25(OH)D was measured in blood samples of 378 mother–child pairs during pregnancy and at birth. Information about children's atopic manifestations during the first 2 years of life was obtained from questionnaires filled out by the parents during pregnancy and annually thereafter. Cord blood regulatory T cells (Treg) were detected by methylation‐specific PCR using a Treg‐specific demethylated region in the FOXP3 gene.
Results
The median maternal 25(OH)D3 level was 22.19 ng/ml (IQR 14.40–31.19 ng/ml); the median cord blood 25(OH)D3 10.95 ng/ml (6.99–17.39 ng/ml). A high correlation was seen between maternal and cord blood 25(OH)D3 levels, both showing a seasonal distribution. Maternal and cord blood 25(OH)D3 was positively associated with children's risk for food allergy within the first 2 years. Further, higher maternal 25(OH)D3 resulted in a higher risk for sensitization against food allergens at the age of two. Cord blood 25(OH)D3 levels were negatively correlated with regulatory T cell numbers.
Conclusion
Our study demonstrates that high vitamin D levels in pregnancy and at birth may contribute to a higher risk for food allergy and therefore argues against vitamin D supplement to protect against allergy.
Summary
Primary antibody deficiencies require lifelong replacement therapy with immunoglobulin (Ig)G to reduce the incidence and severity of infections. Both subcutaneous and intravenous routes of ...administering IgG can be effective and well tolerated. Treatment regimens can be individualized to provide optimal medical and quality‐of‐life outcomes in infants, children, adults and elderly people. Frequency, dose, route of administration, home or infusion‐centre administration, and the use of self‐ or health‐professional‐administered infusion can be tailored to suit individual patient needs and circumstances. Patient education is needed to understand the disease and the importance of continuous therapy. Both the subcutaneous and intravenous routes have advantages and disadvantages, which should be considered in selecting each patient's treatment regimen. The subcutaneous route is attractive to many patients because of a reduced incidence of systemic adverse events, flexibility in scheduling and its comparative ease of administration, at home or in a clinic. Self‐infusion regimens, however, require independence and self‐reliance, good compliance on the part of the patient/parent and the confidence of the physician and the nurse. Intravenous administration in a clinic setting may be more appropriate in patients with reduced manual dexterity, reluctance to self‐administer or a lack of self‐reliance, and intravenous administration at home for those with good venous access who prefer less frequent treatments. Both therapy approaches have been demonstrated to provide protection from infections and improve health‐related quality of life. Data supporting current options in IgG replacement are presented, and considerations in choosing between the two routes of therapy are discussed.
Objectives. To evaluate the influence of low-dose MTX and etanercept treatment on efficacy of measles, mumps and rubella (MMR) revaccination in children with juvenile idiopathic arthritis. Methods. A ...prospective nested case–control study was performed to investigate markers of MMR revaccination induced humoral and cell-mediated immunity in 15 patients with juvenile idiopathic arthritis (ages 6–17 yrs), treated with either low-dose MTX therapy alone or in combination with etanercept. The control group consisted of 22 healthy children. Production of IFN-γ by T memory cells upon in vitro stimulation with measles, mumps and rubella antigens and seroprevalence of virus-specific IgG antibodies were assessed. Medication use, disease activity and patients' comments on side-effects were observed during the period of 6 months before and after revaccination. Results. Low-dose MTX therapy following MMR vaccination proved not to hamper T-cell mediated immunity in vitro. Neither low-dose MTX nor etanercept treatment, given simultaneously with revaccination, markedly interfered with generation of long-lived virus-restricted T cells and protective levels of virus-specific IgG antibodies. No increase in disease activity or medication use was seen within 6 months after MMR revaccination, including JIA patients using etanercept. No overt measles, mumps, rubella or secondary severe infections were noted. Conclusions. Low-dose MTX and etanercept treatment do not seem to interfere with intended outcome of MMR revaccination in children with JIA.
Summary
The importance of serum immunoglobulin (Ig)G concentration in IgG replacement therapy for primary immunodeficiency diseases is established in certain settings. Generally, IgG is infused via ...the intravenous (IVIG) or subcutaneous (SCIG) route. For IVIG infusion, published data demonstrate that higher IgG doses and trough levels provide patients with improved protection from infection. The same conclusions are not yet accepted for SCIG; data from two recent Phase III studies and a recent post‐hoc analysis, however, suggest the same correlation between higher SCIG dose and serum IgG concentration and decreased incidence of infection seen with IVIG. Other measures of clinical efficacy have not been considered similarly. Thus, combined analyses of these and other published SCIG studies were performed; a full comparison of the 13 studies was, however, limited by non‐standardized definitions and reporting. Despite these limitations, our analyses indicate that certain clinical outcomes improve at higher SCIG doses and associated higher serum IgG concentrations, and suggest that there might be opportunity to improve patient outcomes via SCIG dose adjustment.
Background:
Regulatory T cells (Tregs) with stable FOXP3 expression are characterized by a specific demethylated region in the FOXP3 gene (Treg‐specific demethylated region, TSDR). The aim of this ...study was to analyse the influence of prenatal factors on cord blood Treg numbers, as detected by changes in the TSDR demethylation, and the subsequent risk for allergic diseases.
Methods:
Analyses were performed within the LINA study in blood samples from pregnant women (34th gestational week) and in cord blood (n = 346 mother–child pairs). Treg numbers were detected via DNA demethylation in the FOXP3 TSDR. At age 1, total and specific IgE was measured in children's blood. In addition, maternal cytokine production (Th1/Th2/Th17) was analysed. Exposure and disease outcomes were assessed by questionnaires.
Results:
Boys had lower Treg numbers compared with girls (P < 0.001). Parental atopy history, particularly maternal hay fever and paternal asthma were related to lower Treg numbers in cord blood (adj. MR = 0.81, 95% CI = 0.68–0.97; adj. MR = 0.60, 95% CI = 0.45–0.81). Maternal cytokines (IL‐13, IL‐17E and IFN‐γ) and maternal smoking/exposure to tobacco smoke during pregnancy were also associated with decreased cord blood Treg numbers (adj. MR = 0.89, 95% CI = 0.97–1.00). Children with lower Treg numbers at birth had a higher risk to develop atopic dermatitis (adj. OR = 1.55, 95% CI = 1.00–2.41) and sensitization to food allergens (adj. OR = 1.55, 95% CI = 1.06–2.25) during the first year of life.
Conclusions:
These results indicate that both genetic and environmental factors presumably influence the development of foetal Tregs. Low cord blood Treg numbers may predict early atopic dermatitis.
Severe combined immunodeficiency (SCID) is the most severe form of inherited primary immunodeficiency and is a paediatric emergency. Delay in recognising and detecting SCID can have fatal ...consequences and also reduces the chances of a successful haematopoietic stem cell transplant (HSCT). Screening for SCID at birth would prevent children from dying before HSCT can be attempted and would increase the success of HSCT. There is strong evidence to show that SCID fulfills the internationally-established criteria for a condition to be screened for at birth. There is also a test (the T-cell receptor excision circle (TREC) assay) that is now being successfully used in an increasing number of US states to screen for SCID in routine newborn Guthrie samples. Concerted lobbying efforts have highlighted the need for newborn screening (NBS) for SCID, and its implementation is being discussed in Europe both at EU and individual country level, but as yet there is no global mandate to screen for this rare and frequently lethal condition. This paper summarizes the current evidence for, and the success of SCID NBS, together with a review of the practical aspects of SCID testing and the arguments in favour of adding SCID to the conditions screened for at birth.
Evidence-based recommendations for vaccination of paediatric patients with rheumatic diseases (PaedRD) were developed by following the EULAR standardised procedures for guideline development. The ...EULAR task force consisted of (paediatric) rheumatologists/immunologists, one expert in vaccine evaluation, one expert in public health and infectious disease control, and one epidemiologist. A systematic literature review was conducted in MEDLINE, EMBASE, and abstracts of the EULAR and American College of Rheumatology meetings of 2008/9. The level of evidence and strength of recommendation were based on customary scoring systems. Delphi voting was applied to assess the level of agreement between task force members. 107 papers and eight abstracts were used. The majority of papers considered seasonal influenza (41) or pneumococcal (23) vaccination. 26 studies were performed specifically in paediatric patients, and the majority in adult rheumatoid arthritis and systemic lupus erythematosus patients. Fifteen recommendations were developed with an overall agreement of 91.7%. More research is needed on the safety and immunogenicity of (live-attenuated) vaccination in PaedRD, particularly in those using biologicals, and the effect of vaccination on prevention of infections.
Summary
A highly concentrated (20%) immunoglobulin (Ig)G preparation for subcutaneous administration (IGSC 20%), would offer a new option for antibody replacement therapy in patients with primary ...immunodeficiency diseases (PIDD). The efficacy, safety, tolerability and pharmacokinetics of IGSC 20% were evaluated in a prospective trial in Europe in 49 patients with PIDD aged 2–67 years. Over a median of 358 days, patients received 2349 IGSC 20% infusions at monthly doses equivalent to those administered for previous intravenous or subcutaneous IgG treatment. The rate of validated acute bacterial infections (VASBIs) was significantly lower than 1 per year (0·022/patient‐year, P < 0·0001); the rate of all infections was 4·38/patient‐year. Median trough IgG concentrations were ≥ 8 g/l. There was no serious adverse event (AE) deemed related to IGSC 20% treatment; related non‐serious AEs occurred at a rate of 0·101 event/infusion. The incidence of local related AEs was 0·069 event/infusion (0·036 event/infusion, when excluding a 13‐year‐old patient who reported 79 of 162 total related local AEs). The incidence of related systemic AEs was 0·032 event/infusion. Most related AEs were mild, none were severe. For 64·6% of patients and in 94·8% of IGSC 20% infusions, no local related AE occurred. The median infusion duration was 0·95 (range = 0·3‐4·1) h using mainly one to two administration sites median = 2 sites (range = 1–5). Almost all infusions (99·8%) were administered without interruption/stopping or rate reduction. These results demonstrate that IGSC 20% provides an effective and well‐tolerated therapy for patients previously on intravenous or subcutaneous treatment, without the need for dose adjustment.
In 94.8% of IGSC 20% infusions (n=2338) administered to patients with PIDD in this European study, no causally related local AE occurred.
Higher infusion rates or infusion volumes per site were not associated with an increased incidence of causally related local AEs. IGSC 20% provided an effective and well‐tolerated therapy for patients previously on intravenous or subcutaneous treatment, with no dose adjustment.
Summary
Intravenous and subcutaneous immunoglobulins (IVIg and SCIg, respectively) are increasingly used in clinical practice, not only as replacement therapy but also for immunomodulation. ...Physicians have learned that primary immunodeficiency (PID) patients are susceptible to recurrent respiratory tract infections even when appropriately treated with immunoglobulin (Ig) therapy. Further investigation will establish whether a combined therapeutic approach including Ig dose optimization will prevent progressive lung disease in PID. The wear‐off effects observed with IVIg can be minimized by adjusting the dosing regimen. It is also possible to avoid the cyclic wear‐off following transition to SCIg administration. Consideration of benefit versus risk with Ig therapy includes evaluating the potential occurrence of thromboembolic and haemolytic events, which may be more frequent when Ig is administered in high doses and in the presence of pre‐existing risk factors. The ability to select an administration method from IVIg, SCIg or hyaluronidase‐facilitated SCIg infusions provides patient choice and alternatives if one or other administration route is not suitable for a patient. The evolution in indications, applications, and understanding of Ig therapy described here has reinforced the need for robust methods to prioritize Ig use.
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