Passive blood anaphylaxis: subcutaneous immunoglobulins are a cause of ongoing passive anaphylactic reaction

Abstract

BackgroundAllergic, especially anaphylactic, reactions during immunoglobulin replacement therapy are rare, but their pathophysiology and classification remain ambiguous. Recent findings show positive results of skin tests with commercially available immunoglobulins, but target antigens and responsible compounds of the tested immunoglobulins have not been strictly identified.Case description and findingsFour adult patients with recently diagnosed common variable immunodeficiency qualified for standard subcutaneous immunoglobulin replacement therapy regimen. They had no history of receiving immunoglobulins, blood or blood product transfusions. Edema, confluent wheals and erythema were observed at the site of subcutaneous immunoglobulin infusion: typical early and late phase reaction. A transient increase in various passively transferred IgG and IgE antibodies was responsible for misleading positive outcome of the serological testing for active humoral response such as type I allergy, anti-Rh, isohemagglutinins and rheumatoid factor (RF). Although the clinical presentation was very unusual and severe, the retrospective analysis showed no isohemagglutinins, RF and IgE in the patients’ serum before but it was positive after the infusion (median IgE = 18 IU/ml, RF = 8 IU/ml). Type I allergic reaction (laryngeal edema, rhinoconjuctivitis) came out at +14 days of replacement therapy when the patient visited countryside. In the second patient anaphylactic reaction was observed 5 days after ScIg administration, and only when the patient consumed peanuts. Therefore, IgE concentration was measured retrospectively in a series of commercial preparations used in the initial subcutaneous immunoglobulin replacement therapy that caused the adverse event (AE) and it was determined between 138 and 232 IU/ml (kU/l), i.e. 690–2100 IU per g of protein. Specific IgE was within a wide range from 198 (mix of food) to 2809 kUA/l (mix of grass) but many of the tested allergen-specific IgE were class 2 or 3 (i.e. 0.71–17.5 kUA/l).ConclusionsThe case resembles passive cutaneous anaphylaxis and Prausnitz–Küstner reaction but clinical significance of the classical phenomena has not yet been described. This observation indicates that anaphylactic reactions during immunoglobulin replacement therapy may result from IgE or pathological IgG content. Such IgE presence was sporadically reported (34.5–105 IU/ml, i.e. 862.5–1450 IU/g of protein) in intravenous immunoglobulins that are used and monitored by healthcare professionals. In clinical practice the definition of adverse events is inadequate since individual batches of immunoglobulins come with different specificity therefore, they should be classified as transfusion products (not bioequivalents). Such new approach implies establishing (1) new control methods and strategies to ensure introduction of the safety regulations for subcutaneous home self-administration of immunoglobulins as well as (2) guidelines for the prevention of anaphylaxis in patients receiving immunoglobulins (for example peanut).

Anaphylaxis to Subcutaneous Immunoglobulin in a Severe Combined Immunodeficiency Patient

“…Anaphylactic reactions to subcutaneous immunoglobulin preparations are extraordinarily rare and have only been associated with late‐onset allergic reactions. Zdziarski et al reported 4 patients with common variable immune deficiency who presented allergic reactions attributable to IgE or IgG content in the subcutaneous immunoglobulin batch 1 . We present the case of a patient who developed reproducible symptoms compatible with anaphylaxis because of acute‐onset multisystem involvement (skin, respiratory, and gastrointestinal).…”

“…Lina Maria Castano-Jaramillo, MD 1 , Carla Toledo-Salinas, MD 1 , Edwin Pardo-Diaz, MD 1 , Francisco Alberto Contreras-Verduzco, MD 2 , and David Alejandro Mendoza-Hernandez, MD 2 We present the case of a 12-year-old male with a medical history of severe combined immunodeficiency who underwent hematopoietic stem cell transplantation from a haploidentical related donor and remained dependent on replacement immunoglobulin therapy. He was receiving subcutaneous immunoglobulin at home (Subglobin) for the past 3 years.…”

“…Anaphylactic reactions to subcutaneous immunoglobulin preparations are extraordinarily rare and have only been associated with late-onset allergic the subcutaneous immunoglobulin batch. 1 We present the case of a patient who developed reproducible symptoms compatible with anaphylaxis because of acute-onset multisystem involvement (skin, respiratory, and gastrointestinal). Some of the patient's symptoms, such as fever, chills, and myalgias, might be attributable to cytokine-mediated immune response, comprising a mixed anaphylaxis phenotype.…”

Correction to: Passive blood anaphylaxis: subcutaneous immunoglobulins are a cause of ongoing passive anaphylactic reaction

“…Upon publication of the original article [ 1 ], the authors reported the following funding information was omitted: Publication supported by Wroclaw Centre of Biotechnology, programme The Leading National Research Centre (KNOW) for years 2014–2018.…”

Construction and Potential Applications of Biosensors for Proteins in Clinical Laboratory Diagnosis

“…The specific IgG shows an increase about four weeks after infection and lasts for the long term, years sometimes, and could be used as a biomarker for the evaluation of recovery [ 9 , 10 ]. In addition, the Igs are always involved in hypersensitivity of the body [ 11 , 12 ]. For example, IgE can induce type I hypersensitivity, and specific IgEs are detected for the determination of allergens.…”