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Background: The INTERCEPT™ Blood System for Red Blood Cells (RBCs) utilizes amustaline (S‐303) and glutathione (GSH) to inactivate pathogens and leukocytes in transfused RBCs. Treatment‐emergent low titer non‐hemolytic antibodies to amustaline/GSH RBC were detected in clinical trials using a prior version of the process. The amustaline/GSH process was re‐formulated to decrease S‐303 RBC adduct formation.
Study Design and Methods: A standard three‐cell antibody screening panel was modified to include reagent red cells (RRC) with high (S‐303H) or low (S‐303L) S‐303 adduct density as assessed by flow cytometry, representative of the original and current amustaline/GSH treatment processes, respectively. General hospital and RBC transfusion‐dependent patients never exposed, and clinical trial subjects exposed to amustaline/GSH RBC were screened for antibodies to amustaline/GSH RBC using a standardized agglutination assay.
Results: Twelve (0.1%) of 10,721 general hospital and 5 (0.5%) of 998 repeatedly‐transfused patients not previously exposed to amustaline/GSH RBCs expressed natural, low titer (2‐32) IgM and/or IgG (non‐IgG1 or IgG3 isotype) antibodies with acridine (a structural element of amustaline) (n = 14) or non‐acridine (n = 3) specificity. 11 of 17 sera reacted with S‐303L panel RRCs. In clinical studies 81 thalassemia and 25 cardiac surgery patients were transfused with a total of 1085 amustaline/GSH RBCs and no natural or treatment‐emergent S‐303 antibodies were detected.
Conclusion: Standardized RRC screening panels are sensitive for the detection of natural and acquired S‐303‐specific antibodies. Natural low titer antibodies to amustaline/GSH RBC are present in 0.15% of naïve patients. The clinical relevance of these antibodies appears minimal but is under further investigation.
Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.