Université Paris Cité

Severe allergic transfusion reactions to group B/AB plasma or platelets in group O recipients are linked to α-Gal sensitization.

Allergic transfusion reactions (ATR) are potentially lethal adverse events that occur in ∼0.3% to 6% of plasma or platelet transfusions. The main mechanism described is an immunoglobulin E (IgE)-mediated response to donor proteins, such as IgA and haptoglobin in deficient patients. Recently, in a nationwide retrospective observational study, we reported that group O recipients of group B or AB platelet concentrates or plasma were at significantly higher risk of severe ATR than recipients with other ABO combinations. Given the antigenic proximity between group B determinant and the galactose-α-1,3-galactose (α-Gal) epitope, we hypothesize a role for α-Gal IgE-mediated sensitization in these ATR. In this report, we investigated the presence of anti-α-Gal IgE in a cohort of 59 patients with severe ATR. We found that group O recipients of group B or AB blood components (plasma or platelet concentrates) were substantially more likely to exhibit high titers of group B cross-reactive anti-α-Gal IgE than other patients, supporting our hypothesis that α-Gal sensitization underlies these severe ATR. These findings suggest that α-Gal sensitization is an additional mechanism responsible for ATR in major ABO-incompatible transfusion and should be systematically explored in group O patients having received group B/AB plasma or platelets.

Association between group B major ABO-incompatible platelet or plasma transfusion and severe allergic reactions: A nationwide haemovigilance analysis suggesting a role for α-gal syndrome. A Biomedical Excellence for Safer Transfusion Collaborative study.

Severe transfusion reactions to group B-incompatible platelets and plasma possibly related to the α-gal syndrome (AGS) have been recently described. AGS is a potentially severe Immunoglobulin E mediated allergy to mammalian meat and meat-derived products associated with tick bites. The involved allergen, galactose-α-1,3-galactose (α-gal), is antigenically similar to the blood group B antigen. To further assess a potential association between AGS and allergic transfusion reactions (ATRs), we comparatively assessed the frequency of ATRs after plasma or platelet concentrate (PC) transfusion in relation to the degree of ABO compatibility between the recipient and the involved blood component in France. In France, all transfusions are centrally recorded, and ATR reporting is mandatory. Frequencies of severe ATRs involving PC or plasma in relation to ABO group distributions were analysed between 1 January 2022 and 31 December 2024. Among 981,955 PC and 580,230 plasma evaluable transfusions, severe ATRs were significantly higher in group O recipients transfused with group B or AB platelets (relative risk [RR]: 5.06, 95% confidence interval [CI]: 3.27-7.83, p < 0.001) and plasma (RR: 2.15, 95% CI: 1.37-3.36, p < 0.001) while not in group A recipients of group B or AB platelets (RR: 0.95, 95% CI: 0.30-2.96) or plasma (RR: 0.92, 95% CI: 0.45-1.88), when compared to ATR rates in all other recipients of PC or plasma, respectively. In this national retrospective haemovigilance analysis, group B or AB PC or plasma transfused to group O recipients is associated with an increased risk of severe ATRs. Further studies will establish whether AGS is involved in this increased risk.

Editorial: Animal models of allergic diseases: from basic to preclinical research.

Anaesthetic management of patients with pre-existing allergic conditions: a narrative review.

This narrative review seeks to distinguish the clinical patterns of pre-existing allergic conditions from other confounding non-allergic clinical entities, and to identify the potential related risks and facilitate their perioperative management. Follow-up investigation should be performed after a perioperative immediate hypersensitivity to establish a diagnosis and provide advice for subsequent anaesthetics, the main risk factor for perioperative immunoglobulin E (IgE)-mediated anaphylaxis being a previous uninvestigated perioperative immediate hypersensitivity reaction. The concept of cross-reactivity between drugs used in the perioperative setting and food is often quoted, but usually not supported by evidence. There is no reason to avoid propofol in egg, soy, or peanut allergy. The allergenic determinants have been characterised for fish, shellfish, and povidone iodine, but remain unknown for iodinated contrast agents. Iodinated drugs may be used in seafood allergy. Evidence supporting the risk for protamine allergy in fish allergy and in neutral protamine Hagedorn insulin use is lacking. Conversely, cross-reactivity to gelatin-based colloid may occur in α-gal syndrome. Atopy and allergic asthma along with other non-allergic conditions, such as NSAID-exacerbated respiratory disease, chronic urticaria, mastocytosis, and hereditary or acquired angioedema, are not risk factors for IgE-mediated drug allergy, but there is a perioperative risk associated with the potential for exacerbation of the various conditions.

Pork-cat syndrome revealed after surgery: Anaphylaxis to bovine serum albumin tissue adhesive.

Biochemical characterization and immunogenicity of Neureight, a recombinant full-length factor VIII produced by fed-batch process in disposable bioreactors.

Hemophilia A is a X-linked recessive bleeding disorder consecutive to the lack of circulating pro-coagulant factor VIII (FVIII). The most efficient strategy to treat or prevent bleeding in patients with hemophilia A relies on replacement therapy using exogenous FVIII. Commercially available recombinant FVIII are produced using an expensive perfusion technology in stainless steel fermenters. A fed-batch fermentation technology was recently developed to produce 'Neureight', a full-length recombinant human FVIII, in Chinese hamster ovary (CHO) cells. Here, we investigated the structural and functional integrity and lack of increased immunogenicity of Neureight, as compared to two commercially available full-length FVIII products, Helixate and Advate, produced in baby hamster kidney or CHO cells, respectively. Our results demonstrate the purity, stability and functional integrity of Neureight with a standard specific activity of 4235 ± 556 IU/mg. The glycosylation and sulfation profiles of Neureight were similar to that of Advate, with the absence of the antigenic carbohydrate epitopes α-Gal and Neu5Gc, and with sulfation of Y1680, that is critical for FVIII binding to von Willebrand factor (VWF). The endocytosis of Neureight by human immature dendritic cells was inhibited by VWF, and its half-life in FVIII-deficient mice was similar to that of Advate, confirming unaltered binding to VWF. In vitro and in vivo assays indicated a similar immunogenicity for Neureight, Advate and Helixate. In conclusion, the production of full-length FVIII in a fed-batch fermentation mode generates a product that presents similar biochemical, functional and immunogenic properties as products developed using the classical perfusion technology.

High incidence of cetuximab-related infusion reactions in head and neck patients.

Cetuximab is crucial in the management of squamous cell carcinoma of the head and neck of patients. Grade 3-4 cetuximab-induced infusion reactions (CI-IRs) occur in 2% of patients with colorectal cancer. Despite the 2.7% CI-IR rate in the EXTREME trial, higher rates were reported in small series of patients with head and neck squamous cell carcinoma (HNSCC) (6%-18%). There is an urgent need to better appraise the natural history and the predictive factors for CI-IRs in patients with HNSCC exposed to cetuximab. The medical records from patients with HNSCC (n=428) treated by cetuximab at Gustave Roussy from January 2013 to December 2015 were reviewed. The impact of potential risk factors was analysed. Out of 428 patients, 24 patients (5.4%) presented CI-IR, including grade 3-4 (95.7%); about 21% (5/24) requiring intensive care unit referral and quasi all occurred within the first cycle (21/24). In a multivariate analysis, the occurrence of grade 3-4 CI-IR was associated with tobacco and alcohol history (p=8.5e-3) and with prior allergy history (p=2.9e-3). CI-IRs tended to be associated with poor overall survival in patients with recurrent and metastatic HNSCC and with a higher number of further lines of chemotherapy. In real life, CI-IRs appear far more common in patients with HNSCC (5.4%) than reported in prospective trials. This is the largest series of patients ever focusing on the risk of CI-IR in patients with HNSCC. Prior allergy history and tobacco history are associated with CI-IR and could be used to better allocate treatment. Further prospective data are required to confirm these findings.

Cross-reactivity to fish and chicken meat - a new clinical syndrome.

Fish is one of the most allergenic foods. While clinical cross-reactivity among different fishes is a widely accepted feature of fish allergy, associations with other food allergies are not well understood. This study aims at analyzing the relevance of clinical cross-reactivity between fish and chicken meat in patients with allergy to chicken meat without sensitization to hen's eggs. Patients with food allergy to fish and chicken meat (n = 29) or chicken meat only (n = 7) were recruited. IgE-reactive chicken proteins were identified (Edman, MS analysis) and quantified (ELISA). Allergens were used in IgE ELISA and skin testing. Chicken parvalbumin and two new allergens, aldolase and enolase, were identified at 12, 40, and 50 kDa, respectively. They were recognized by sIgE of 61%, 75%, and 83% of all patient sera which were in the majority of the cases positive for the fish homologues as well. Fish and chicken meat allergens were highly cross-reactive while high inhibition rates with fish or chicken allergens correlated with the patients' primary sensitization to fish or chicken. In cooked or roasted foods, enolase and aldolase were detectable in chicken breast while parvalbumin was detectable in chicken legs and wings. Fish and chicken meat are cross-reactive foods; both fish-allergic and chicken meat-allergic patients might be at risk of developing a food allergy to chicken meat or to fish, respectively. This clinical phenomenon is proposed to be termed 'fish-chicken syndrome' with cross-reactive allergens involved being parvalbumins, enolases, and aldolases.

The reducing end of alpha Gal oligosaccharides contributes to their efficiency in blocking natural antibodies of human and baboon sera.

Synthetic galactosyl oligosaccharides were tested for their ability to inhibit the cytotoxic reaction of human and baboon natural antibodies on PK15 cells in culture. Methyl-alpha-Gal gave weak inhibition, Gal alpha 1-3Gal substantially inhibited the reaction (400muM), and Gal alpha 1-3Gal beta 1-4GLcNAc was ten times more efficient (30 muM). The modification from alpha to beta anomeric configuration of the nonreducing end resulted in a complete loss of activity, while substitutions at the reducing end induced only a partial loss of activity. These observations suggest that natural anti-alphaGal antibodies recognize the epitope from its nonreducing end, but that substitutions at the reducing terminus can modify the antibody-binding capacity. Modified tri- and tetrasaccharides are better inhibitors than the disaccharide but not as good as Gal alpha 1-3Gal beta 1-4GlcNAc. The reducing terminus therefore contributes some energy to the reaction, indicating that certain oligosaccharides will be of more potential clinical use than others.