Jones VM, Nakahara H, Choudhary SK, Dunbar NM, Szczepiorkowski ZM, et al.
Transfusion •
The bites of certain tick species can induce galactose-α-1,3-galactose (alpha-gal) IgE formation. Individuals with alpha-gal IgE can become allergic to meat, a condition termed alpha-gal syndrome. Alpha-gal is structurally related to B antigen. Recent case reports (Gilstad et al., 2023 and Miller et al., 2024) suggest that transfusing group B plasma or platelets to group O individuals with alpha-gal IgE can trigger severe allergic transfusion reactions. However, mechanistic evidence is lacking. A 76-year-old group O man undergoing heart surgery became profoundly hypotensive after receiving 50 mL of a group B platelet unit. He recovered with diphenhydramine treatment. We investigated potential causes of anaphylaxis (alpha-gal syndrome; IgA deficiency; protamine, and rocuronium allergies). The platelet unit and patient samples were analyzed by flow cytometry. Indirect basophil activation tests (iBATs) were performed on the patient's plasma. The patient's serum tryptase level spiked, consistent with anaphylaxis. His serum tested positive for alpha-gal IgE (1.49 kU/L). Flow cytometric analyses demonstrated that: (1) the transfused platelets expressed substantial B antigen, and (2) the patient's plasma contained IgE-recognizing alpha-gal and B antigen > A antigen. In iBATs, resting allogeneic basophils incubated with the patient's plasma showed equivalent (albeit weak) activation when stimulated with either alpha-gal or B antigen. We report a case of anaphylactic shock in an O patient transfused with a B platelet unit. The in vitro data suggest, but do not prove, that the reaction was mediated by recipient alpha-gal IgE. Further studies are needed to establish whether transfusion-related alpha-gal syndrome ("TRAGS") is a true clinical entity.
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology •
Hypersensitivity reactions to antineoplastic agents may lead to discontinuation of first-line treatments. Rapid drug desensitization (RDD) allows for a safe reintroduction in patients who are allergic to them. To evaluate the safety and efficacy of the Brigham and Women's Hospital's 12-step RDD in a Portuguese patient population with cancer and to identify markers associated with breakthrough reactions (BTRs) to platins. We conducted a retrospective review of desensitizations undertaken at the Immunoallergology Day-Care Unit of the Santa Maria Hospital in Lisbon, Portugal, from July 2008 to July 2019. Adult patients with cancer and with immediate hypersensitivity reactions were included. Skin testing was performed to platins, trastuzumab, and cetuximab. The 12-step protocol was used for most patients, and a shorter protocol was used in 9 patients who were taxane-reactive to resume regular infusions. A total of 1471 RDDs were performed in 272 patients to 136 platins, 124 taxanes, 13 monoclonal antibodies, and 10 other drugs. Skin test results were positive in 127 of patients who were platin-reactive (95.3%) and negative in patients who were cetuximab- and trastuzumab-reactive. There were 141 BTRs during RDD (9.6% of infusions), 79.4% induced by platins with the majority having mild reactions (68.8%). There were 8 patients who were paclitaxel-reactive, and who completed a shorter protocol and resumed regular infusions successfully. Multiple platin infusions (cutoff: ≥10) and total immunoglobulin E greater than or equal to 100 U/mL were identified as independent risk factors for BTRs in patients who were platin-reactive. This large single-center study confirmed the safety and efficacy of the 12-step RDD protocol in a diverse cancer population, providing evidence of its universal applications. Total immunoglobulin E is a potentially useful biomarker to identify high-risk patients who are platin-reactive.
Iweala OI, Choudhary SK, Addison CT, Batty CJ, Kapita CM, et al.
The Journal of allergy and clinical immunology •
Alpha-gal-containing glycolipids activate basophils sensitized with plasma from alpha-gal allergic subjects in an IgE-dependent manner suggesting a role for glycolipid in the effector phase of IgE-mediated food allergy.
The journal of allergy and clinical immunology. In practice •
Biological agents are used in the treatment of neoplastic, autoimmune, and inflammatory diseases and their clinical applications are becoming broader. Following their increased utilization, hypersensitivity reactions linked to these drugs have become more frequent, sometimes preventing the use of first-line therapies. The clinical presentation of hypersensitivity reactions to biological agents ranges from mild cutaneous manifestations to life-threatening reactions. In this scenario, rapid desensitization is a groundbreaking procedure that enables selected patients to receive the full treatment dose in a safe way, in spite of their immediate hypersensitivity reaction to the drug, and protects them against anaphylaxis. The aim of this review is to update and discuss some of the main biological agents used in clinical practice (rituximab, trastuzumab, cetuximab, ofatumumab, tocilizumab, brentuximab, omalizumab, and tumor necrosis factor alpha inhibitor agents) and their associated hypersensitivity reactions, including clinical presentations, diagnosis, and treatment in the acute setting. In addition, novel management options with rapid desensitization are presented.
Decellularized biologic matrices are plausible biomedical materials for the bioengineering in liver transplantation. However, one of the concerns for safe medical application is the lack of objective assessment of the immunogen within the materials and the in vivo immune responses to the matrices. The purpose of this study was the production of immunogen-reduced and biocompatible matrices from porcine liver. In the present study, 0.1% SDS solution was effective for removing DNA fragments and sequences encoding possible immunogenic and viral antigens within the matrices. The PCR analysis showed that galactose-α-1,3 galactose β-1,4-N-acetylglucosamine (1,3 gal), swine leukocyte antigen (SLA), and porcine endogenous retrovirus (PERV) were completely removed in the matrices. Collagen and glycosaminoglycans (GAGs) were preserved over 63%-71%, respectively, compared to those of native liver. The implanted decellularized tissues showed minimal host responses and naturally degraded within 10 weeks. In this study, we produced immunogen-reduced and biocompatible extracellular matrices from porcine liver. Although future investigations would be required to determine the mechanism of the host reaction, this study could provide useful information of porcine liver-derived biologic matrices for liver researches.
