The interleukin-6 -174promoter polymorphism is associated with long-term kidney allograft survival

The interleukin-6 -174promoter polymorphism is associated with long-term kidney allograft survival.BackgroundTh1-dependent effector mechanisms may be responsible for allograft rejection. Recently, interleukin-6 (IL-6) has been shown to antagonize CD4+ T cells to effector Th2 cells and, in the process, differentiate them into Th1 cells.MethodsTo assess the role of IL-6 in long-term allograft survival, 158 patients after first cadaveric kidney transplantation were analyzed for the biallelic –174G→C promoter polymorphism of the IL-6 gene.ResultsCarriers of the –174C-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 –174GG-genotype (48/54 = 88.9%). The –174GC/CC-genotype retained its negative impact on graft survival when other established prognostic factors and further cytokine polymorphisms (-308TNF-α, TGF-β1 codon 10 & 25, -592/-819/-1082IL-10 and +874IFN-γ) were considered simultaneously.ConclusionsSince the clinical impact on transplant outcome seems as important as matching for histocompatibility antigens, genotyping of the IL-6 -174polymorphism may offer a new method for identifying patients at increased risk of allograft loss

Characteristics of lapsed German whole blood donors and barriers to return four years after the initial donation

Background: The aim of the study was to identify characteristics of lapsed donors 4 years after the initial donation as well as self-reported barriers to return for further blood donations. Methods: A random number of 8,000 blood donors, donating for the German Red Cross Blood Service Baden-Wurttemberg - Hessen, were asked to fill in a self-administered questionnaire. The response rate was 38.5%. Donors were categorized as ”lapsed’ if they had not donated within the last 24 months. The odds of being a lapsed donor were determined in a multivariate logistic regression. Results: Multivariate analysis showed that lapsed donors were more likely to be female, between 26 and 33 years old, not employed, have moved, and were dissatisfied with the last donation experience. Furthermore, lapsed donors were less likely to have family members or friends who also donate blood. Medical reasons and having moved to another city were the most frequently named reasons preventing lapsed donors from continuing to donate blood. Conclusion: The importance of medical reasons and having moved was rated much higher than in previous studies. We conclude that barriers to return may vary considerably between countries and blood services. Therefore, donor surveys are required to guide reactivation campaigns

Donor deferral rates after the implementation of a new German blood donor questionnaire

Background: The implementation of a new national German blood donor questionnaire was proposed to improve donor and recipient safety. Methods: We compared deferral/exclusion rates of whole blood donors before (May 2010, n = 64,735) and after (May 2011, n = 71,687) the implementation of a new blood donor questionnaire. Considering seasonal variations, analysis was performed with respect to collection site (mobile vs. fixed), sex, donor status (first-time vs. repeat), age, and the frequencies of sexual risk behavior and other reasons for deferral. Results: We observed a statistically significant increase (p < 0.001) of the overall deferral/exclusion rate from 6.2 to 8.1%, irrespective of type of collection site (fixed: from 6.0 to 8.5%; mobile: from 6.2 to 8.0%), sex (females: from 7.5 to 9.9%; males: from 5.1 to 6.6%), donor status (first-time donors: from 19.7 to 24.7%; repeat donors: from 4.6 to 6.3%) or age (18–29 years: from 9.1 to 11.7%; 60–71 years: from 5.1 to 6.6%). Confidential self-exclusion increased from 0.08 to 0.14% (p < 0.001). Besides risk behavior, various medical reasons could be identified that explain this increase. Conclusions: The new blood donor questionnaire resulted in an increased deferral/exclusion of all donor groups. Thus the impact on future blood supply must be considered carefully, and long-term studies and investigation of donor acceptance will be needed

Common clonal origin of conventional T cells and induced regulatory T cells in breast cancer patients

Regulatory CD4+ T cells (Treg) prevent tumor clearance by conventional T cells (Tconv) comprising a major obstacle of cancer immune-surveillance. Hitherto, the mechanisms of Treg repertoire formation in human cancers remain largely unclear. Here, we analyze Treg clonal origin in breast cancer patients using T-Cell Receptor and single-cell transcriptome sequencing. While Treg in peripheral blood and breast tumors are clonally distinct, Tconv clones, including tumor-antigen reactive effectors (Teff), are detected in both compartments. Tumor-infiltrating CD4+ cells accumulate into distinct transcriptome clusters, including early activated Tconv, uncommitted Teff, Th1 Teff, suppressive Treg and pro-tumorigenic Treg. Trajectory analysis suggests early activated Tconv differentiation either into Th1 Teff or into suppressive and pro-tumorigenic Treg. Importantly, Tconv, activated Tconv and Treg share highly-expanded clones contributing up to 65% of intratumoral Treg. Here we show that Treg in human breast cancer may considerably stem from antigen-experienced Tconv converting into secondary induced Treg through intratumoral activation

Motivation zur Vollblutspende während pandemischer Ereignisse

Auch während Pandemien müssen die Blutspendedienste kontinuierlich BlutspenderInnen rekrutieren, um die Versorgung mit Blutprodukten zu gewährleisten. Während im Anschluss an andere Katastrophen wie Erdbeben oder Terroranschlägen die Spendebereitschaft meist sprunghaft ansteigt, zeigte sich in der Vergangenheit bei beginnenden Pandemien zunächst ein Rückgang des Spendeaufkommens. Viele SpenderInnen fürchten eine Infektion oder eine Schwächung ihres Immunsystems und bleiben zu Hause. Auch fällt es den Blutspendediensten zunächst schwer, die gewohnte Anzahl an mobilen Spendeterminen zu organisieren, wodurch das Spendenaufkommen zurückgeht. In der aktuellen SARS-CoV2-Pandemie betrug dieser Rückgang in vielen Ländern mehr als 10%. SpenderInnen, die auch während einer Pandemie spenden, sind in der Regel erfahrener und besitzen bereits eine ausgebildete Spenderidentiät. Viele dieser SpenderInnen berichten, dass sie gezielt einen Beitrag zur Überwindung der Krise leisten möchten. Auch während einer Pandemie ist demnach eine hohe Solidarität unter Blutspendern zu finden. Potentielle ErstpenderInnen lassen sich durch die unsicheren Rahmenbedingungen dagegen von einer Spende eher abhalten und es bedarf gezielter Rekrutierungsstrategien unter Einsatz von Social-Media-Kanälen, um neue SpenderInnen zu gewinnen. Erste Befunde unter deutschen Blutspendern lassen hierbei eine hohe Rückkehrintention der ErstspenderInnen erwarten. Um die Blutversorgung auch während einer Pandemie aufrechterhalten zu können, sollten die Blutspendedienste neben der Rekrutierung von ErstspenderInnen versuchen, schnell die Anzahl ihrer Spendetermine zu erhöhen. Die Ansprache bestehender SpenderInnen sollte vor allem die Verunsicherung reduzieren und das Vertrauen in die Blutspendedienste stärken. Je größer das Vertrauen in die Spendeeinrichtung ausfällt, desto geringer ist die Risikowahrnehmung der SpenderInnen. Auch sollten alternative Kontaktwege etwa über Messenger-Dienste getestet werden, da diese eine schnelle Ansprache erlauben

Changes in the Whole Blood Donor Population in South-West Germany: 2010 versus 2016

Background: In the recent past, the discrepancy between blood supply and future demand may have been overestimated. Nevertheless, as medical progress develops rapidly, it will be essential to permanently monitor ongoing demographic changes in the donor population and re-evaluate retention and recruiting strategies. Thus, it was the aim of the current study to compare first time donor (FTD) characteristics and their return rates, whole blood donations in total and annual donation frequencies 2010 versus 2015/2016. Furthermore, we evaluated whether over the same observation period, medical reasons for deferral underwent a change (2010 versus 2015). Methods: The return probability of FTD within 12 months was analysed in 2010 and 2015 with respect to successful donation versus deferral and, furthermore, FTD age was determined. Total number of whole blood (WB) donations were investigated and age distribution was compared 2010 versus 2013 versus 2016. WB donation frequencies were calculated with respect to age and gender in 2010 and 2016. In a second analysis, medical reasons for deferral were differentiated into 14 categories and a possible impact of time (2010 versus 2015) on the respective percentage was studied. Results: We observed a significant decline of the FTD return rate from 42.5% to 38.8% in successful donors while the rate remained unchanged in deferred FTD. At the same time the mean FTD age decreased from 29.1 ± 11.6 to 28.5 ± 11.7 years in 2016. Analysis of total WB donations revealed an increase of donations from donors ≥ 60 years, a constant percentage from donors < 30 years but a declining proportion of donors from 30-59 years of age from 2010 to 2013 to 2016. In parallel, annual mean WB donation frequencies decreased over time. Deferrals due to travel history increased significantly from 2010 to 2015 both in FTD and repeat donors (RD). Conclusion: There is a detectable ongoing demographic change as well as a change of medical deferral reasons in our WB donor population. Our data prove a need for a re-evaluation of retention and recruitment strategies since previous marketing campaigns seem to have neglected the age group 30-59 years. This must be addressed in further studies as this age group will be highly relevant for assuring future blood supplies since donor recruitment from adolescents will be limited due to declining birth rates. Furthermore, deferral due to travel history is increasing significantly. Thus we will require further studies on the possible impact on donor retention

The Mannheim Cord Blood Bank: Experiences and Perspectives for the Future

BACKGROUND AND METHODS: As a source of hematopoietic stem cells, cord blood (CB) is an alternative to bone marrow or peripheral blood stem cells (PBSC). The Mannheim Cord Blood Bank has currently stored about 1,750 allogeneic CB units. Here we report our experiences and discuss future perspectives of CB banking. We analyzed CB units for nucleated cell (NC), mononucleated cell (MNC) and CD34+ cell count, volume, colony-forming units (CFU-GM) as well as ethnic background of the donor. Transplanted CB units were analyzed for patient and transplant characteristics and compared to stored CB units. RESULTS: Only 25% of all collected CB units met storage criteria. Main reasons for exclusion were: i) insufficient volume (57.7%), ii) delayed arrival at the processing site (19.2%) and iii) little cell count (7.2%). Up to now 36 CB units have been released for transplantation mainly to children (62%). Transplant indications were hematological diseases, immune deficiencies and metabolic diseases. Transplanted CB units showed significantly higher cell counts compared to stored units (NC: 12.5 vs. 7.2 × 10(8), MNC: 4.7 vs. 2.9 × 10(8), CD34+ cells: 3.3 vs. 1.8 × 10(6), mean; p < 0.001 each) and were found more often in ethnic minority groups (36 vs. 20%; p = 0.04). CONCLUSIONS: Even though cell count and volume are key parameters for the eligibility of CB units, our data indicate that the ethnic background of the donor also plays a major role. Collection and processing of CB should be optimized in order to gain maximum volume and cell counts