The ABO blood group system is associated with differential susceptibility to thrombotic vascular diseases. ABO is also known to be a strong trans-protein quantitative trait locus for plasma proteins involved in cell adhesion and hemostasis. To further investigate these associations, we integrated epigenomic, genomic, and proteomic data from the Milieu Intérieur cohort. We used the rs8176719 SNP to classify donors as either type O or non-O, and used linear models to compare levels of 229 plasma proteins in 400 donors, including age, sex, cytomegalovirus serostatus, and secretor status as covariates. We observed increased levels of soluble E-selectin and decreased levels of von Willebrand Factor (vWF) in O donors compared with non-O donors. By performing an epigenome-wide association study, we identified 23 differentially methylated CpG sites between blood types, which were all located in the ABO gene. Notably, CpG sites in the ABO promoter region of type O donors were less methylated than those of the non-O donors. Using mediation analysis, we found that these differences in DNA methylation partially explained the effects of blood group on differential E-selectin and vWF plasma levels. We find differentially methylated CpG sites between blood types and provide new evidence that ABO blood group status affects circulating levels of specific proteins.

The authors declare no conflicts of interest.

BackgroundCutibacterium acnes contaminated platelet concentrates (PCs) are transfused due to late detection during culture‐based screening. C. acnes has been implicated in mild adverse transfusion reactions; however, it harbors multiple virulence genes and can cause chronic infections in the clinical setting. Since the PC storage environment enhances virulence gene expression in bacteria like Staphylococcus aureus, this study aimed to evaluate the impact of PC storage on C. acnes virulence and its potential to cause chronic infections.Study design and methodsPCs and media were inoculated with C. acnes (BPNBT‐19195 and BPNBT‐19329) and S. aureus (CBS 2016‐05, control) PC isolates. Following incubation for 5 days (20–24°C/agitation), bacterial virulence was compared in the Bombyx mori (silkworm) model. Additionally, silkworm innate response (hemolymph melanization and superoxide dismutase activity (SOD)), adhesion to HEK293T epithelial cells, and differential expression of virulence genes involved in tissue invasion (hyl, mce) and persistence (roxP, lipase) were assessed in C. acnes samples.ResultsPC‐derived C. acnes caused significantly lower larval mortality, hemolymph melanization, and SOD activity compared to media‐derived counterparts; conversely, PC‐derived S. aureus caused significantly higher larval mortality. Furthermore, PC‐derived C. acnes displayed higher adherence to HEK293T cells and heightened virulence gene expression compared to media controls.DiscussionOur data demonstrated that the PC milieu enhances the ability of C. acnes to adhere to mammalian epithelia and promotes the expression of genes involved in invasion and persistence in host tissue, potentially priming this bacterium to cause chronic infections in transfusion patients, which warrants further investigation.

BackgroundDuring pregnancy, exposure to fetal red blood cell antigens can trigger alloimmunization. To enable safe transfusion of compatible blood for pregnant individuals where urgent surgery might be necessary, blood bank standards mandate a valid blood type and antibody screening every 72 h (“3‐day rule”). This practice requires frequent blood drawings contributing to patient discomfort and costs. To investigate if this practice is required, we evaluated the proportion of pregnant individuals who develop clinically significant alloantibodies within 72 h of a previous negative antibody screen.Study Design and MethodsRetrospective cohort of RhD‐positive pregnant individuals with initial negative antibody screens, undergoing repeated screens at variable intervals. Seroconversion rates were compared with healthy male blood donors. Characteristics of pregnant individuals with and without seroconversion were analyzed.ResultsAmong 8659 RhD‐positive pregnant individuals with initial negative antibody screens, 56 (0.6%) converted to a positive antibody screen, while only 15 (0.2%) developed clinically significant alloantibodies. Of these 15, only one converted within 3 days of testing, while others converted within 5–95 days. Two of the 15 women received a blood transfusion, 8–97 days before seroconversion. No male donors seroconverted during 9 months of follow up. Pregnant individuals with seroconversion were more likely to have systemic lupus erythematosus and antiphospholipid antibody syndrome.DiscussionOnly one pregnant individual developed clinically significant alloantibodies within 72 h of a negative screening, compared to none of the control group. For pregnant individuals without recent transfusion, extending antibody screening intervals to 1 week appears safe.

Pathogen reduction technologies (PRTs) have the potential to reduce the risk of emerging transfusion transmissible infections. Evaluating PRT activity against hepatitis B virus (HBV) presents some unique challenges due to the lack of robust model systems. Surrogate viruses (e.g., duck HBV) can be used, but may differ from the human pathogen in ways that influence susceptibility to a given PRT. Whole blood (WB) collected from volunteers was spiked with human plasma from deferred HBV-positive donors. Spiked WB was then treated with the nucleic acid crosslinking compound S-303 or left untreated. Additional physical and chemical treatments were also assessed. Plasma prepared from the spiked WB was used to inoculate human hepatocyte cultures isolated from chimeric mice with humanized livers. Culture medium was monitored over time for hepatitis B surface antigen (HBsAg) and viral DNA. Cell lysates were analyzed for evidence of covalently closed circular (ccc) DNA. The culture system faithfully measured infectious HBV in blood components. S-303 treatment of HBV-spiked WB prevented infection of hepatocyte cultures, as monitored by HBsAg expression, at concentrations as low as 0.125 mM of S-303 or with incubation times as short as 1 h. Additionally, S-303 treatment prevented the accumulation of T5 exonuclease-resistant HBV DNA in inoculated hepatocytes, suggesting that S-303 prevents establishment of HBV cccDNA. This model mimics transfusion transmission by using donor-derived HBV and mouse-passaged human hepatocytes, allowing evaluation of the efficacy of different PRTs against authentic human HBV isolates. We found S-303 to be a potent inactivator of HBV.

BackgroundBlood service providers use deferral policies to reduce the risk of transfusion‐transmitted infections, but policy effectiveness depends on donors' honesty in disclosing risk behaviors. Identifying specific social factors within men who have sex with men (MSM) may provide insight into noncompliance with sexual behavioral deferral criteria.MethodsWe identified a sample of 136 recent blood donors from a large behavioral surveillance survey of MSM in New Zealand. Univariate analyses were used to identify factors associated with self‐reported noncompliance before a two‐step hierarchical regression assessed whether MSM‐related social factors added to the prediction of noncompliance, compared to only considering background characteristics.ResultsIncorporating the MSM‐related social factors significantly enhanced the model fit, explaining 23.2% additional variance in noncompliance (Nagelkerke R2 = 0.331, p = .002). Only MSM who were more open about their sexuality had increased odds of noncompliance (Odds ratio 5.25, 95% Confidence Interval 1.78–15.48, p = .003). Full‐time employment remained a predictor of lower noncompliance in the final model (OR 0.19, 95% CI 0.05–0.69, p = .012).ConclusionThis exploratory evidence suggests that blood service providers should consider the broader social context, particularly openness about sexuality, in understanding noncompliance with time‐based sexual behavior donor deferral criteria. This “outness” in MSM donors likely reflects confidence in making disclosure decisions based on their perceived HIV risk, challenging the notion that noncompliance necessarily arises from discomfort or lack of knowledge about policies. Future research should explore the gap between perceived risk and policy understanding to better address MSM donors' complex decision‐making processes.