International forum. an investigation of iron status in blood donors

No abstract availabl

Naturally occurring antibodies against serum amyloid A reduce IL-6 release from peripheral blood mononuclear cells

<div><p>Serum amyloid A (SAA) is a sensitive inflammatory marker rapidly increased in response to infection, injury or trauma during the acute phase. Resolution of the acute phase and SAA reduction are well documented, however the exact mechanism remains elusive. Two inducible SAA proteins, SAA1 and SAA2, with their variants could contribute to systemic inflammation. While unconjugated human variant SAA1α is already commercially available, the variants of SAA2 are not. Antibodies against SAA have been identified in apparently healthy blood donors (HBDs) in smaller, preliminary studies. So, our objective was to detect anti-SAA and anti-SAA1α autoantibodies in the sera of 300 HBDs using ELISA, characterize their specificity and avidity. Additionally, we aimed to determine the presence of anti-SAA and anti-SAA1α autoantibodies in intravenous immunoglobulin (IVIg) preparations and examine their effects on released IL-6 from SAA/SAA1α-treated peripheral blood mononuclear cells (PBMCs). Autoantibodies against SAA and SAA1α had a median (IQR) absorbance OD (A₄₅₀) of 0.655 (0.262–1.293) and 0.493 (0.284–0.713), respectively. Both anti-SAA and anti-SAA1α exhibited heterogeneous to high avidity and reached peak levels between 41–50 years, then diminished with age in the oldest group (51–67 years). Women consistently exhibited significantly higher levels than men. Good positive correlation was observed between anti-SAA and anti-SAA1α. Both anti-SAA and anti-SAA1α were detected in IVIg, their fractions subsequently isolated, and shown to decrease IL-6 protein levels released from SAA/SAA1α-treated PBMCs. In conclusion, naturally occurring antibodies against SAA and anti-SAA1α could play a physiological role in down-regulating their antigen and proinflammatory cytokines leading to the resolution of the acute phase and could be an important therapeutic option in patients with chronic inflammatory diseases.</p></div

Naturally occurring antibodies against serum amyloid A reduce IL-6 release from peripheral blood mononuclear cells - Fig 5

<p><b>Inhibition of IL-6 release by anti-SAA (A, B) and anti-SAA1α (C, D) isolated antibodies on hrSAA- and hrSAA1α- stimulated PBMCs.</b> Dose-dependent effects of isolated anti-SAA and anti-SAA1α antibodies on IL-6 release from hrSAA-treated PBMCs (<b>A, B</b>) and hrSAA1α-treated PBMCs (<b>C, D</b>). Mean±SD from five HBDs is shown for each treatment in panels A and C, while corresponding individual graphs from HBDs are shown in panels B and D. * p<0.05, ** p<0.01. PBMCs from 5 HBDs were isolated and incubated for 5h with the indicated agents. HBDs, healthy blood donors; IVIg, intravenous immunoglobulin; PBMCs, peripheral blood mononuclear cells; SAA, serum amyloid A.</p

Levels of anti-SAA and anti-SAA1α antibodies.

<p><b>(A)</b> Boxplots show the median OD (A₄₅₀) and IQR for anti-SAA and anti-SAA1α levels in the sera of 300 HBDs (220 male and 80 female). The number of samples in each group is indicated in brackets. Whiskers represent 5^th and 95^th percentile. Medians between groups were compared using Man Whitney U-test. *p <0.05, ** p <0.01 and *** p <0.001. <b>(B)</b> Shown are medians for anti-SAA and anti-SAA1α levels in HBDs sera based on age distribution (4 groups). The number of samples in each group is indicated in brackets. HBDs, healthy blood donors; SAA, serum amyloid A.</p

Amino acid alignments of hrSAA and hrSAA1α.

<p>Amino acid alignments of hrSAA and hrSAA1α.</p

Anti-SAA and anti-SAA1α levels in IVIg.

<p>Octagam IVIg was serially diluted in sample dilution buffer (dilution range of 1.56–50 μg/ml) and analyzed for the presence of anti-SAA and anti-SAA1α antibodies using <i>in-house</i> ELISA. IVIg, intravenous immunoglobulin; SAA, serum amyloid A.</p

Naturally occurring antibodies against serum amyloid A reduce IL-6 release from peripheral blood mononuclear cells - Fig 3

<p><b>Immunoglobulin avidity of anti-SAA (A) and anti-SAA1α (B) antibodies.</b> Avidity of IgG antibodies against SAA and SAA1α was determined in 6 HBDs samples (3 male, 3 female; as indicated in brackets) using increasing concentration of NaCl in sample dilution buffer. As control, 1% BSA in PBS+0.1% Tween-20 with the same NaCl concentrations, was used. BSA, bovine serum albumin; HBDs, healthy blood donors; PBS; phosphate buffered saline; SAA, serum amyloid A.</p

Specificity assays for anti-SAA and anti-SAA1α antibodies.

<p>Specificity assays for anti-SAA and anti-SAA1α antibodies.</p

Demographics of healthy blood donors.

<p>Demographics of healthy blood donors.</p

Pathogen reduction of blood components during outbreaks of infectious diseases in the European Union: an expert opinion from the European Centre for Disease Prevention and Control consultation meeting.

International audiencePathogen reduction (PR) of selected blood components is a technology that has been adopted in practice in various ways. Although they offer great advantages in improving the safety of the blood supply, these technologies have limitations which hinder their broader use, e.g. increased costs. In this context, the European Centre for Disease Prevention and Control (ECDC), in co-operation with the Italian National Blood Centre, organised an expert consultation meeting to discuss the potential role of pathogen reduction technologies (PRT) as a blood safety intervention during outbreaks of infectious diseases for which (in most cases) laboratory screening of blood donations is not available. The meeting brought together 26 experts and representatives of national competent authorities for blood from thirteen European Union and European Economic Area (EU/EEA) Member States (MS), Switzerland, the World Health Organization, the European Directorate for the Quality of Medicines and Health Care of the Council of Europe, the US Food and Drug Administration, and the ECDC. During the meeting, the current use of PRTs in the EU/EEA MS and Switzerland was verified, with particular reference to emerging infectious diseases (see Appendix). In this article, we also present expert discussions and a common view on the potential use of PRT as a part of both preparedness and response to threats posed to blood safety by outbreaks of infectious disease