Functional Assessment of Vitamin D Status by a Novel Metabolic Approach: The Low Vitamin D Profile Concept.

BACKGROUND: Determining serum 25-hydroxyvitamin D [25(OH)D], 24,25-dihydroxyvitamin D [24,25(OH)2D] and the vitamin D metabolite ratio (VMR) allows the identification of individuals with a low vitamin D metabolite profile. Here, we evaluated if such a functional approach provides superior diagnostic information to serum 25(OH)D alone. METHODS: 25(OH)D, 24,25(OH)2D, and the VMR were determined in participants of the DESIRE (Desirable Vitamin D Concentrations, n = 2010) and the LURIC (Ludwigshafen Risk and Cardiovascular Health, n = 2456) studies. A low vitamin D metabolite profile (vitamin D insufficiency) was defined by a 24,25(OH)2D concentration <1.2 ng/mL (<3 nmol/L) and a VMR <4%. Parathyroid hormone (PTH) and bone turnover markers were measured in both cohorts, whereas 10-year mortality data was recorded in LURIC only. RESULTS: The median age in DESIRE and LURIC was 43.3 and 63.8 years, respectively. Median 25(OH)D concentrations were 27.2 ng/mL (68.0 nmol/L) and 15.5 ng/mL (38.8 nmol/L), respectively. Serum 25(OH)D deficiency, defined as <20.2 ng/mL (<50 nmol/L), was present in 483 (24.0%) and 1701 (69.3%) participants of DESIRE and LURIC, respectively. In contrast, only 77 (3.8%) and 521 (21.2%) participants had a low vitamin D metabolite profile. Regardless of the serum 25(OH)D concentration, a low vitamin D metabolite profile was associated with a significantly higher PTH, accelerated bone metabolism, and higher all-cause mortality than an unremarkable vitamin D metabolite profile. CONCLUSIONS: The personalized assessment of vitamin D status using a functional approach better identifies patients with accelerated bone metabolism and increased mortality than the use of a fixed 25(OH)D cutoff of 20 ng/mL (50 nmol/L).

Pilot Study to Gain First Indications for the Impact of a 3-Month's Oral Intake of a Sucrosomial Iron Supplement on Hemoglobin in Iron-Deficient Blood Donors.

Introduction: Regular whole blood donors often suffer from iron deficiency (ID) or iron deficiency anemia due to the loss of 200-300 mg of iron with each donation. Hemoglobin (Hb) as donor eligibility criterion reflects iron stores only poorly. ID in blood donors is typically prevented or treated with orally administered ferrous salts, which frequently cause gastrointestinal side effects. A high daily oral iron dose is counterproductive due to hepcidin upregulation. Oral sucrosomial iron (sucriron) is encapsulated ferric pyrophosphate that may be an option for blood donors due to its supposed high bioavailability and good tolerability. Methods: This monocentric single-cohort pilot study included fifty whole blood donors (divided into premenopausal women, postmenopausal women, and men) who did not meet Hb donation criteria. Participants aged 18-65 years with ferritin <30 ng/mL and venous Hb <12.5 g/dL in women and Hb <13.5 g/dL in men received oral sucriron (30 mg iron) for 90-120 days. Primary endpoints were the increase of Hb and ferritin. Results: Forty-seven participants completed the study. With the limitation that no control group was included, there was a substantial overall median increase of 0.94 g/dL Hb and 4.97 ng/mL ferritin (standardized on 90 days of iron intake). These value improvements were likewise observed in each of the subgroups. sucriron was very well tolerated, with almost no gastrointestinal side effects identified. Conclusion: A clear increase of Hb and ferritin was observed after the intake of sucriron, so it may be a reasonable and useful alternative to traditional oral iron therapy. The ease of administration, pleasant taste, dietary supplement status, and, most importantly, good tolerability highlight the value of sucriron supplementation.

Allele-specific long-range sequencing as a method for ABO haplotyping in clinical blood group diagnosis and immunohematology research.

BACKGROUND: Safe transfusion therapy requires accurate testing of blood donors and recipients to determine their ABO blood group compatibility. Genotyping does not always clarify serological blood typing discrepancies and conventional PCR methods are not suitable to identify ABO haplotypes. Therefore, an allele-specific long-range sequencing-based typing method was established. METHODS: Study samples (n = 100) and six patient samples were ABO phenotyped and screened for specific single nucleotide polymorphisms (SNP) in the ABO gene. Based on identified heterozygous SNPs in intron 1 (12897G>A), 2 (437C>T) or 4 (102C>A, 1511G>T) both ABO alleles were investigated separately using a high-fidelity long-range PCR system and Sanger sequencing. The alleles were correlated to the ABO phenotypes determined. RESULTS: Direct sequencing of allelic PCR products up to 6743 bases has been successful in discriminating common combinations of the ABO*A1.01, ABO*A2.01, ABO*B.01, ABO*O.01.01, ABO*O.01.02 and ABO*O.02.01 alleles. 10 out of 64 haplotypes were found to be not previously described. The uncommon ABO*AW.31.01 and the unusual O alleles ABO*O.05 and ABO*O.02.03 alleles were detected in patient samples, resolving the initial inconclusive serologic ABO typing results. CONCLUSION: This method is an effective tool for analyzing ABO haplotypes. Applicable for ABO molecular diagnostics and immunohematology research it may help to improve pre-transfusion blood type testing.

Lower Levels of ABO Anti-A and Anti-B of IgM, IgG and IgA Isotypes in the Serum but Not the Saliva of COVID-19 Convalescents.

Individuals with ABO type O, naturally possessing anti-A and anti-B antibodies in their serum, are underrepresented among patients infected with SARS-CoV-2 compared with healthy controls. The ABO antibodies might play a role in the viral transmission. Therefore, we aimed to quantify anti-A/anti-B, including their subclasses IgM, IgG and IgA, in the serum and saliva of Caucasians (n = 187) after mild COVID-19 to compare them with individuals who had never been infected with SARS-CoV-2. Two samples were collected within two months after the diagnosis (median days: 44) and two months later. ABO antibodies were determined by flow cytometry. Additionally, total IgA in saliva and antibodies specific to SARS-CoV-2 were tested by ELISA. COVID-19 convalescents had significantly lower levels of anti-A/anti-B IgM, IgG and IgA in their serum than control subjects (p < 0.001). Interestingly, no significant differences were observed in saliva. ABO antibody levels remained stable over the period considered. No relation of ABO to the level of SARS-CoV-2-specific antibodies was observed. Total IgA was lower in convalescents than in controls (p = 0.038). Whereas ABO antibodies in the saliva may not contribute to the pathogenesis of COVID-19, individual pre-existing high serum concentrations of anti-A/anti-B may have a protective effect against SARS-CoV-2 infection.