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Summary: Routine ABO blood group typing of apparently healthy individuals sporadically uncovers unexplained mixed‐field reactions. Such blood group discrepancies can either result from a haematopoiesis‐confined or body‐wide dispersed chimerism or mosaicism. Taking the distinct clinical consequences of these four different possibilities into account, we explored the responsible cause in nine affected individuals. Genotype analyses revealed that more than three‐quarters were chimaeras (two same‐sex females, four same‐sex males, one sex‐mismatched male), while two were mosaics. Short tandem repeat analyses of buccal swab, hair root and nail DNA suggested a body‐wide involvement in all instances. Moreover, genome‐wide array analyses unveiled that in both mosaic cases the causative genetic defect was a unique copy‐neutral loss of heterozygosity encompassing the entire long arm of chromosome 9. The practical transfusion‐ or transplantation‐associated consequences of such incidental discoveries are well known and therefore easily manageable. Far less appreciated is the fact that such findings also call attention to potential problems that directly ensue from their specific genetic make‐up. In case of chimerism, these are the appearance of seemingly implausible family relationships and pitfalls in forensic testing. In case of mosaicism, they concern with the necessity to delineate innocuous pre‐existent or age‐related from disease‐predisposing and disease‐indicating cell clones. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study aimed to describe motives as well as donation experiences and the intention to return for further donations of German whole blood donors who donated at the beginning of the COVID‐19 pandemic. Materials and Methods: To describe motives and donor experiences, a retrospective survey was conducted among whole blood donors that had a donation appointment at the German Red Cross Blood Donation Service in the first 4 weeks of the pandemic. A donor questionnaire including 17 retrospective questions was sent to 7500 donors. Donor motivation and donor experiences were compared for different donor groups using chi‐square statistics. Finally, in an ordinal logistic regression model predictors for the intention to return were identified. Results: More than half of the participating donors (56.9%) wanted to contribute to the fight against the pandemic by donating blood. Most of the donors were satisfied with their last donation experience and felt safe during the blood donor appointment. However, some donors would have liked more information on how to deal with the pandemic (20.3%). Intention to return for further donations was strongly associated with overall satisfaction (OR: 1.67, CI: 1.47–1.90) and the feeling of being safe during blood donation (OR: 1.33, CI: 1.05–1.68). Conclusion: Donor satisfaction with the last donation was high and the vast majority of donors felt very safe. However, those donors who felt unsafe expressed a low intention to return and blood donation services should therefore carefully monitor donor satisfaction. [ABSTRACT FROM AUTHOR]

Abstract Background Interleukin-6 (IL-6) promoter polymorphisms at positions -597(G→A), -572(G→C) and -174(G→C) were shown to have a clinical impact on different major diseases. At present PCR-SSP protocols for IL-6 -597/-572/-174haplotyping are elaborate and require large amounts of genomic DNA. Findings We describe an improved typing technique requiring a decreased number of PCR-reactions and a reduced PCR-runtime due to optimized PCR-conditions. Conclusion This enables a fast and efficient determination of IL-6 -597/-572/-174haplotypes in clinical diagnosis and further evaluation of IL-6 promoter polymorphisms in larger patient cohorts.

BACKGROUND: White blood cell (WBC)-associated antibodies can lead to severe pulmonary transfusion reactions (transfusion-related acute lung injury [TRALI]). Investigation of a large number of blood donor samples using the standard granulocyte immunofluorescence test (GIFT) and granulocyte agglutination test (GAT) proved to be difficult to perform due to the time-consuming process and the large quantity of test cells required. This study describes the novel flow cytometric GIFT (Flow-GIFT) method for a rapid detection of granulocyte antibodies by flow cytometric analysis. STUDY DESIGN AND METHODS: A total of 141 sera were analyzed for the presence of granulocyte antibodies that were previously associated with suspected TRALI. As test cells whole blood samples from human neutrophil antigen (HNA)-typed donors were isolated using cell sedimentation in a ficoll density gradient. WBCs were incubated with the respective serum and binding of antibodies to the test cells was detected using fluorescein isothiocyanate–conjugated anti-human antibody. Standard GIFT and GAT were performed as reference methods. RESULTS: Seven sera containing anti-HNA-3a, CD16, and HLA Class I were negative in the standard GIFT and eight sera containing anti-HNA-2a, anti-CD16, and anti-HLA Class I were not detected in the GAT. The novel Flow-GIFT was able to detect all granulocyte antibodies, which were only detectable in a combination of standard GIFT and GAT. In serial dilution tests, the Flow-GIFT detected the antibodies at higher dilutions than the reference methods GIFT and GAT. CONCLUSION: The Flow-GIFT method permits rapid detection of granulocyte antibodies requiring fewer donor test cells. This method is ideal for automation and will potentially open the way for screening of granulocyte antibodies in a large donor population. [ABSTRACT FROM AUTHOR]

Background. Th1-dependent effector mechanisms may be responsible for allograft rejection. Recently, interleukin-6 (IL-6) has been shown to antagonize CD4[sup +] T cells to effector Th2 cells and, in the process, differentiate them into Th1 cells. Methods. To assess the role of IL-6 in long-term allograft survival, 158 patients after first cadaveric kidney transplantation were analyzed for the biallelic [sup -174]G→C promoter polymorphism of the IL-6 gene. Results. Carriers of the [sup -174]C-allele (genotype GC/CC) had an inferior three-year graft survival (71/104 = 68.3%; P = 0.0059) with a 3.7-fold increased relative risk of graft loss compared to carriers of the [sup -174]GG-genotype (48/54 = 88.9%). The [sup -174]GC/CC-genotype retained its negative impact on graft survival when other established prognostic factors and further cytokine polymorphisms ([sup -308]TNF-α, TGF-β1 codon 10 & 25, [sup -592/-819/-1082]IL-10 and [sup +874]IFN-γ) were considered simultaneously. Conclusions. Since the clinical impact on transplant outcome seems as important as matching for histocompatibility antigens, genotyping of the IL-6 [sup -174]polymorphism may offer a new method for identifying patients at increased risk of allograft loss. [ABSTRACT FROM AUTHOR]

Kidney transplant recipients with the interleukin-6 (IL-6) GGG/GGG promoter (-597/-572/-174)genotype were shown to have a better long-term outcome. Further, the same (-597/-572/-174)genotype was found to be associated with less IL-6 production in healthy control subjects. To verify this observation in potential kidney transplant recipients, IL-6 production was analyzed in 85/142 hemodialysis patients. We could not confirm an impaired IL-6 secretion in carriers of the GGG/GGG (-597/-572/-174)genotype and propose a significantly lower IL-6 production in hemodialysis patients versus healthy control subjects to explain this. However, we suggest subsequent studies of IL-6 production in kidney allograft recipients to further elucidate the pathophysiological relevance of IL-6 for transplant outcome.

Background and Aim of the Study: Rejection is a plausible cause of failure of allograft valves, but has not been demonstrated unequivocally in humans. A cross-sectional study has been conducted on the frequency of anti-human leukocyte antigen (HLA) antibodies in order to identify any correlation with allograft function in adult patients, following the Ross procedure., Methods: Anti-HLA antibodies were determined during regular follow up (median 1.1 years postoperatively) in a random sample of 197 patients (151 males, 46 females; mean age 46 +/- 13 years). Panel-reactive antibodies (PRA) were determined by cytotoxicity testing; anti-HLA class 2 antibodies (HLA2AB) were determined by ELISA in a subgroup of 94 patients. Echocardiographic examinations were performed during the first visit and at a median of 6.8 years postoperatively., Results: The prevalence of positive antibody tests was 47% for PRA and 52% for HLA2AB. A slight deterioration of allograft valve function occurred between the two examinations (median maximal pressure gradient increased from 9 mmHg to 13 mmHg, p < 0.001; median degree of regurgitation increased from zero to trivial, p = 0.020). The degree of regurgitation was slightly, but significantly, higher in PRA-positive patients at both examinations (p = 0.008 and p = 0.038). No relationship was observed between PRA status and pressure gradients, nor between HLA2AB status and allograft valve function. Neither were any other risk factors for allograft valve deterioration identified., Conclusion: Subtle, clinically irrelevant and temporally stable differences with regard to regurgitation across the allograft were observed between PRA-positive and -negative patients. These findings neither proved nor disproved rejection, but rather suggested that a slow deterioration of allograft valve function was complex, and most likely multifactorial.

Background and Aim of the Study: Rejection is thought to contribute to the degeneration of valved homografts. A novel cryopreserved decellularized homograft valve (SynerGraft; CryoLife, Inc.) offers the unique opportunity to gain new insight into the immunology of homograft implantation and its significance for valve function., Methods: Twenty-four patients (group I; mean age 37 +/- 11 years) underwent implantation of a pulmonary SynerGraft and were examined at one and six months postoperatively; 22 patients (group II; mean age 41 +/- 17 years) with conventional homografts served as controls. Temperature, C-reactive protein (CRP) levels and white blood cell count (WBC) were studied perioperatively. Follow up included echocardiography and anti-human leukocyte antigen (HLA) class I antibody determination., Results: Significantly lower temperatures were measured in group I (p = 0.019). CRP level and WBC each increased postoperatively, but did not differ between groups. During follow up, none of the SynerGraft patients became positive for anti-HLA antibodies, compared with 66% of controls (p = 0.011). Homograft diameter and valve orifice area were decreased significantly at one month after surgery in groups I and II (25 +/- 1 versus 18 +/- 3 mm; 25 +/- 1 versus 19 +/- 2 mm, respectively; p <0.001 both groups). Transvalvular pressure gradients significantly increased during follow up., Conclusion: Implantation of the SynerGraft pulmonary homograft appeared safe, and though evidence was found of a reduced immunologic response after SynerGraft implantation this (unexpectedly) did not translate into any hemodynamic advantage. Hence, factors other than rejection appear as the main contributions to the observed functional changes.