Food Allergy and Anaphylaxis Research (7)Allergic Rhinitis and Sensitization (4)Mast cells and histamine (4)Vector-borne infectious diseases (2)Xenotransplantation and immune response (2)
Filip AB, Mahmood L, Tilly C, Foster HR, Jackson F, et al.
Annals of emergency medicine •
North American pit viper antivenoms, CroFab® and ANAVIP®, contain galactose-α-1,3-galactose (α-GAL) oligosaccharide. We compared adverse drug reactions, including presumed anaphylaxis, following administration of these antivenoms and investigated biological plausibility of these antivenoms leading to anaphylaxis in α-GAL-immunoglobulin (Ig) E-sensitized individuals. We performed 2 studies. A retrospective chart review from the Arkansas Poison Center (May 2021 to July 2023) identified adverse drug reactions and presumed anaphylaxis in patients treated with crotaline antivenom. Two allergists (JK, LM), blinded to the antivenom used, adjudicated presumed anaphylaxis cases. To assess whether antivenoms could activate basophils from α-GAL-IgE-sensitized individuals, basophil activation tests were performed on blood from 5 α-GAL-IgE-sensitized participants with a history of mammalian meat allergy. Basophil activation was assessed by %CD63 upregulation. Adverse drug reactions without presumed anaphylaxis occurred in 7 out of 171 (4.1%) Fab recipients versus 8 out of 37 (21.6%) F(ab') recipients (Δ=17.5%, 95% confidence interval [CI] [4.0 to 31.0]). Presumed anaphylaxis was observed in 3 out of 171 (1.8%) for Fab and 6/37 (16.2%) for F(ab') (Δ=14.3%, 95% CI 2.5 to 26.2). In the basophil activation tests, the mean EC for basophil CD63 activation was 144-fold higher for Fab (mean, [standard deviation]; 647 μg/mL of antivenom [627]) compared to F(ab') (4.48 μg/mL of antivenom [2.75]). We demonstrate a substantial incidence of adverse drug reactions and presumed anaphylaxis to crotaline antivenoms in an α-GAL endemic region, with F(ab') antivenom associated with more reactions than F(ab). Clinicians in α-GAL endemic regions should be cautious in the use of antivenoms, especially for patients with α-GAL allergy.
Venkat PG, Nehrbas JF, Bortz PS, Platts-Mills TA, Behm BW, et al.
JGH open : an open access journal of gastroenterology and hepatology •
Ustekinumab, a monoclonal antibody (mAb) used to treat inflammatory bowel disease, has been associated with immediate hypersensitivity reactions during first intravenous infusion. While rare, the mechanism for these reactions is unclear. IgE to the oligosaccharide galactose-α-1,3-galactose (α-gal) is a cause of allergy to mammalian meat and other mammalian products that express α-gal. Given that ustekinumab (Stelara) is produced in murine SP2/0 cells, a cell line known to introduce α-gal during post-translational modification, we hypothesized that α-gal could explain some of these reactions. We describe six patients with Crohn's disease who experienced acute reactions during ustekinumab infusion and were found to have IgE specific to α-gal. Serum or cells from a separate group of α-gal IgE-sensitized patients with red meat allergy were used for in vitro experiments to investigate ustekinumab allergenicity. ImmunoCAP binding assays confirmed that IgE from four red meat allergic patients, but not controls, bound to ustekinumab on the solid phase. This binding was inhibited by the α-gal-containing glycoprotein beef thyroglobulin. Basophil activation tests (BAT), carried out to assess functional activity, revealed dose-dependent activation with ustekinumab from four α-gal-sensitized individuals, but not controls. Two other mAbs produced in SP2/0 cells (cetuximab and infliximab) as well as a representative mAb produced in Chinese Hamster Ovary (CHO) cells (vedolizumab) were evaluated as comparators, with the mAbs from SP2/0 but not CHO cells eliciting BAT activity. Pre-existing IgE to α-gal may account for some first-dose infusion reactions to ustekinumab. Screening for α-gal sensitization in patients with alpha-gal syndrome should be considered prior to ustekinumab infusion.
The journal of allergy and clinical immunology. In practice •
IgE to galactose-alpha-1,3-galactose (alpha-gal) is linked to tick bites and an important cause of anaphylaxis and urticarial reactions to mammalian meat. The alpha-gal syndrome (AGS) is recognized as being common in the southeastern United States. However, prevalence studies are lacking and open questions remain about risk factors and clinical presentation of alpha-gal sensitization. Here we characterized the prevalence as well as the presentation and risk factors of AGS and alpha-gal IgE sensitization in adults in central Virginia recruited without regard to the history of allergic disease. Adults in central Virginia, primarily University of Virginia Health employees, were recruited as part of a COVID-19 vaccine study. Subjects provided at least one blood sample and answered questionnaires about medical and dietary history. We used ImmunoCAP for IgE assays and assessed the ABO blood group by reverse typing using stored serum. We also investigated biobanked serum from COVID-19 patients. Median age of the 267 enrollees was 42 years, 76% were female, and 43 (16%) were sensitized to alpha-gal (cutoff of 0.1 IU/mL), of which mammalian meat allergy was reported by seven (2.6%). Sensitized subjects (1) were older, (2) had higher total IgE levels but a similar frequency of IgE to common respiratory allergens, and (3) were more likely to report tick bites than were nonsensitized subjects. Among those who were sensitized, alpha-gal IgE levels were higher among meat-allergic than nonallergic subjects (geometric mean, 9.0 vs 0.5 IU/mL; P < .001). Mammalian meat and dairy consumption was common in individuals with low-level sensitization. In central Virginia, AGS is a dominant cause of adult food allergy with a prevalence approaching or exceeding 2%.