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BackgroundLow serum levels of 25-hydroxyvitamin D3 are associated with an increased risk of respiratory tract infections (RTIs). Clinical trials with vitamin D3 against various infections have been carried out but data are so far not conclusive. Thus, there is a need for additional randomised controlled trials of effects of vitamin D3 on infections.ObjectiveTo investigate if supplementation with vitamin D3 could reduce infectious symptoms and antibiotic consumption among patients with antibody deficiency or frequent RTIs.DesignA double-blind randomised controlled trial.SettingKarolinska University Hospital, Huddinge.Participants140 patients with antibody deficiency (selective IgA subclass deficiency, IgG subclass deficiency, common variable immune disorder) and patients with increased susceptibility to RTIs (>4 bacterial RTIs/year) but without immunological diagnosis.InterventionVitamin D3 (4000 IU) or placebo was given daily for 1 year.Primary and secondary outcome measuresThe primary endpoint was an infectious score based on five parameters: symptoms from respiratory tract, ears and sinuses, malaise and antibiotic consumption. Secondary endpoints were serum levels of 25-hydroxyvitamin D3, microbiological findings and levels of antimicrobial peptides (LL-37, HNP1–3) in nasal fluid.ResultsThe overall infectious score was significantly reduced for patients allocated to the vitamin D group (202 points) compared with the placebo group (249 points; adjusted relative score 0.771, 95% CI 0.604 to 0.985, p=0.04).LimitationsA single study centre, small sample size and a selected group of patients. The sample size calculation was performed using p=0.02 as the significance level whereas the primary and secondary endpoints were analysed using the conventional p=0.05 as the significance level.ConclusionsSupplementation with vitamin D3 may reduce disease burden in patients with frequent RTIs.

The importance of vitamin D in immunologic processes has recently emerged, but whether it has any impact on the course of allogeneic hematopoietic stem cell transplantation (HSCT) has not been determined. Reports indicate that HSCT recipients, particularly children, often suffer from vitamin D deficiency. This study investigated the role of vitamin D in 123 children undergoing HSCT from 2004 to 2011. Vitamin D (ie, serum calcidiol) was analyzed in collected cryostored samples. Patients were grouped according to pre-HSCT calcidiol level: insufficient (<50 nm/L, n = 38) and sufficient (≥50 nm/L, n = 85). Older children who underwent transplants from January through June and children of Middle Eastern or African origin were more commonly found in the insufficient group. Acute grades II to IV graft-versus-host disease occurred more frequently in the vitamin D sufficient group (47% versus 30%, P = .05), whereas no difference was demonstrated for chronic graft-versus-host disease. The neutrophil granulocytes rose significantly faster in the vitamin D sufficient group. No difference in lymphocyte counts, immunoglobulin levels, or infectious disease burden during the first year post-HSCT were observed. Among children with malignancies, overall survival was significantly better in the sufficient group (87% versus 50%, P = .01). In addition, rejection (0% versus 11%, P = .06) and relapse (4% versus 33%, P = .03) rates were lower in patients with sufficient vitamin D levels. To conclude, vitamin D may have an important impact on the outcome of pediatric HSCT, particularly in patients with malignant disease. Further studies investigating whether vitamin D acts as an immunomodulator or is merely a surrogate marker of patient health or nutritional status are warranted.

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BackgroundVitamin D is considered to be important for a healthy immune system. The aim of this study was to test the hypothesis that vitamin D supplementation reduces number of respiratory tract infections (RTIs) and prolong the time to the first RTI in adult patients with frequent RTIs.MethodsWe performed a post hoc analysis of a randomized, placebo-controlled and double-blinded study, where adult patients with a high burden of RTIs were randomized to placebo or vitamin D (4000 IE/day for 1 year, n = 124 in the per protocol cohort presented here).ResultsVitamin D supplementation increased the probability to stay free of RTI during the study year (RR 0.64, 95 % CI 0.43–0.94). Further, the total number of RTIs was also reduced in the vitamin D-group (86 RTIs) versus placebo (120 RTIs; p = 0.05). Finally, the time to the first RTI was significantly extended in the vitamin D-group (HR 1.68, 95 % CI 1.03–2.68, p = 0.0376).ConclusionVitamin D supplementation was found to significantly increase the probability of staying infection free during the study period. This finding further supports the notion that vitamin D-status should be monitored in adult patients with frequent RTIs and suggests that selected patients with vitamin D deficiency are supplemented. This could be a safe and cheap way to reduce RTIs and improve health in this vulnerable patient population.The original trial was registered at http://www.clinicaltrials.gov (NCT01131858).

Phosphoglucomutase 3 (PGM3) is an enzyme converting N-acetyl-glucosamine-6-phosphate to N-acetyl-glucosamine-1-phosphate, a precursor important for glycosylation. Mutations in the PGM3 gene have recently been identified as the cause of novel primary immunodeficiency with a hyper-IgE like syndrome. Here we report the occurrence of a homozygous mutation in the PGM3 gene in a family with immunodeficient children, described already in 1976. DNA from two of the immunodeficient siblings was sequenced and shown to encode the same homozygous missense mutation, causing a destabilized protein with reduced enzymatic capacity. Affected individuals were highly prone to infections, but lack the developmental defects in the nervous and skeletal systems, reported in other families. Moreover, normal IgE levels were found. Thus, belonging to the expanding group of congenital glycosylation defects, PGM3 deficiency is characterized by immunodeficiency, with or without increased IgE levels, and with variable forms of developmental defects affecting other organ systems.

The primary aim was to study the relationship between individual serum levels of 25-hydroxyvitamin D and 4b-hydroxycholesterol, which is an endogenous biomarker of the drug-metabolizing CYP3A enzymes. In addition, the relationship between this biomarker and inflammation, measured as C-reactive protein (CRP), was investigated. Serum samples were used from a recently performed clinical trial in patients with antibody deficiency or increased susceptibility to respiratory tract infections that were randomized to either placebo or high-dose (4000 IU/day) vitamin D for 12 months. One hundred sixteen patients were included in the final analyses, and serum samples collected 6 months after study start were analyzed. At this time point, 25-hydroxyvitamin D levels were found to range between 10 and 284 nM. Individual levels of 25-hydroxyvitamin D as well as CRP were compared with 4b-hydroxycholesterol levels. In addition, all participants were genotyped for two polymorphisms (Taq1 and Foq1) in the vitamin D receptor gene. There was no significant correlation between individual serum levels of 25-hydroxyvitamin D and 4b-hydroxycholesterol. However, a moderate, but statistically significant, negative correlation between CRP and 4b-hydroxycholesterol levels was observed. This study in patients with highly variable serum levels of 25-hydroxyvitamin D could not reveal any relationship between vitamin D and 4b-hydroxycholesterol, an endogenous biomarker of CYP3A activity. However, the negative correlation between CRP and 4b-hydroxycholesterol supports earlier experimental results that inflammation may suppress hepatic CYP3A activity, a finding of potentially high clinical relevance that warrants further exploration.