Jacobs JW, Kaufman RM, Schwartz JY, Hall E, Tahiri T, et al.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons •
Alpha-gal syndrome (AGS) is an IgE-mediated hypersensitivity to the oligosaccharide galactose-α-1,3-galactose, acquired through tick bites and increasingly recognized as a cause of allergic reactions to mammalian-derived medical products. Every major transplant modality creates distinct conditions under which sensitized patients may encounter alpha-gal, yet AGS knowledge has developed almost entirely outside the transplant literature. In conventional solid organ transplantation, risk arises primarily from perioperative exposures to porcine-derived heparin, gelatin-based hemostatic agents, and other mammalian-derived materials. In xenotransplantation, the well-characterized role of alpha-gal as the principal xenoantigen has driven development of glycoprotein alpha-galactosyltransferase 1-knockout swine, but the distinct IgE-mediated pathway that defines AGS has received little attention. Hematopoietic stem cell transplantation introduces questions about conditioning-related immune remodeling of preexisting IgE sensitization, rabbit antithymocyte globulin as an underrecognized alpha-gal exposure, and transfusion-related alpha-gal syndrome when group B or AB plasma-containing blood products are transfused to susceptible patients. Cellular therapy manufacturing workflows that use animal-derived ancillary materials represent a further theoretical exposure pathway. Importantly, detectable anti-alpha-gal IgE does not invariably predict clinical reactivity, and the most appropriate clinical approach is risk stratification rather than reflexive exclusion. Generating the evidence base to support such stratification will require collaboration across allergy, transplant, and transfusion medicine.
Wang B, Sierad LN, Mercuri JJ, Simionescu A, Simionescu DT, et al.
Engineered regeneration •
Mitral valve (MV) tissue engineering is still in its early stage, and one major challenge in MV tissue engineering is to identify appropriate scaffold materials. With the potential of acellular MV scaffolds being demonstrated recently, it is important to have a full understanding of the biomechanics of the native MV components and their acellular scaffolds. In this study, we have successfully characterized the structural and mechanical properties of porcine MV components, including anterior leaflet (AL), posterior leaflet (PL), strut chordae, and basal chordae, before and after decellularization. Quantitative DNA assay showed more than 90% reduction in DNA content, and (GS) lectin immunohistochemistry confirmed the complete lack of porcine -Gal antigen in the acellular MV components. In the acellular AL and PL, the atrialis, spongiosa, and fibrosa trilayered structure, along with its ECM constitutes, i.e., collagen fibers, elastin fibers, and portion of GAGs, were preserved. Nevertheless, the ECM of both AL and PL experienced a certain degree of disruption, exhibiting a less dense, porous ECM morphology. The overall anatomical morphology of the strut and basal chordae were also maintained after decellularization, with longitudinal morphology experiencing minimum disruption, but the cross-sectional morphology exhibiting evenly-distributed porous structure. In the acellular AL and PL, the nonlinear anisotropic biaxial mechanical behavior was overall preserved; however, uniaxial tensile tests showed that the removal of cellular content and the disruption of structural ECM did result in small decreases in maximum tensile modulus, tissue extensibility, failure stress, and failure strain for both MV leaflets and chordae.
Humoral immunity to pathogens and other environmental challenges is paramount to maintain normal health, and individuals lacking or unable to make antibodies are at risk. Recent studies indicate that many human protective antibodies are against carbohydrate antigens; however, little is known about repertoires and individual variation of anti-carbohydrate antibodies in healthy individuals. Here we analyzed anti-carbohydrate antibody repertoires (ACARs) of 105 healthy individual adult donors, aged 20-60 from different ethnic backgrounds to explore variations in antibodies, as defined by binding to glycan microarrays and by affinity purification. Using microarrays that contained > 1,000 glycans, including antigens from animal cells and microbes, we profiled the IgG and IgM ACARs from all donors. Each donor expressed many ACAs, but had a relatively unique ACAR, which included unanticipated antibodies to carbohydrate antigens not well studied, such as chitin oligosaccharides, Forssman-related antigens, globo-type antigens, and bacterial glycans. We also saw some expected antibodies to ABO(H) blood group and α-Gal-type antigens, although these also varied among individuals. Analysis suggests differences in ACARs are associated with ethnicity and age. Thus, each individual ACAR is relatively unique, suggesting that individualized information could be useful in precision medicine for predicting and monitoring immune health and resistance to disease.
