100629 - Severe IgE-Mediated Anaphylactic Shock to Rabbit-Derived Anti-Thymocyte Globulin (Grafalon®) During Kidney Transplantation in a Patient with Rabbit Allergy

We report a case of severe IgE-mediated perioperative anaphylaxis to rabbit-derived antithymocyte globulin (Grafalon®) (rATG) during induction immunosuppression for living donor kidney transplantation. A 34-year-old male patient with end-stage renal disease due to reflux nephropathy, on hemodialysis since 2021, developed grade IV anaphylactic shock within minutes of rATG infusion. The reaction required aggressive resuscitation with intravenous fluids and high-dose vasopressors and led to abortion of the transplant, resulting in loss of the donor kidney. Acute serum tryptase measured during the event was elevated at 14.8 µg/L, normalizing on follow-up (5.59 µg/L). Specific IgE testing revealed sensitization to rabbit epithelium (6.92 kUA/L) and urine proteins (4.58 kUA/L), and skin prick testing confirmed a positive reaction to rabbit hair. Other potential perioperative triggers, including latex and chlorhexidine, were excluded or not tested as they had not been administered prior to rATG infusion. Skin prick testing with rATG remained negative, and basophil activation testing with rATG is planned but results are currently pending.

Despite the negative skin test to rATG, no alternative trigger for the perioperative anaphylaxis could be identified. The presence of rabbit sensitization suggests a possible IgE-mediated mechanism related to environmental exposure to rabbit allergens. However, negative skin testing does not exclude hypersensitivity to biologic agents such as rATG. In addition to classical IgE-mediated reactions, biologics may induce mast cell activation through alternative pathways, including complement activation with generation of anaphylatoxins (C3a, C5a),  IgG-mediated mechanisms, or direct mast cell activation via receptors such as Mas-related G protein–coupled receptor X2 (MRGPRX2). These mechanisms may result in clinical anaphylaxis indistinguishable from IgE-mediated reactions. Therefore, while rabbit sensitization supports an IgE-mediated process, non–IgE-mediated mast cell activation cannot be excluded in the present case.

Rabbit-derived antithymocyte globulin is a polyclonal IgG preparation widely used for induction immunosuppression in kidney transplantation, particularly in patients at increased immunological risk. Although generally well tolerated, severe hypersensitivity reactions remain rare but potentially life-threatening complications. 

With the increasing use of biologics in transplantation and immunotherapy, awareness of rare but severe IgE-mediated reactions remains crucial, and preexisting sensitization should be considered in individualized risk-adapted induction strategies.