title: Immunosafety of recombinant human C1-inhibitor in hereditary angioedema: evaluation of ige antibodies.
abstract: BACKGROUND
  Recombinant human C1-inhibitor (rhC1INH) purified from milk of transgenic rabbits is used for the treatment of acute attacks in patients with hereditary angioedema (HAE) due to C1-inhibitor (C1INH) deficiency.
  
  
  OBJECTIVE
  The objective was to investigate the risk of rhC1INH inducing IgE antibodies or eliciting anaphylactic reactions.
  
  
  METHODS
  In subjects treated with rhC1INH, we retrospectively analysed the frequency and clinical relevance of pre-exposure and potentially newly induced IgE antibodies against rabbit and other animal allergens including cow's milk by the ImmunoCAP(®) Specific IgE blood test system.
  
  
  RESULTS
  130 HAE patients and 14 healthy subjects received 300 administrations of rhC1INH, 65 subjects (47.4 %) on one occasion; 72 (52.6 %) on at least two occasions (range 2-12; median 2). Five subjects had pre-existing anti-rabbit epithelium IgE; the subject with the highest levels and a previously undisclosed rabbit allergy developed an anaphylactic reaction upon first exposure to rhC1INH, whereas the other four subjects with lower pre-existing IgE levels (Class 1-3), did not. No other anaphylactic reactions were identified in any of the subjects exposed to rhC1INH. Analysis of post-exposure samples revealed that the risk of inducing new or boosting existing IgE responses to rabbit or cow's milk allergens was negligible.
  
  
  CONCLUSIONS
  The propensity of rhC1INH to induce IgE antibodies following repeated administration of rhC1INH is low. Subjects with substantially elevated anti-rabbit epithelium IgE antibodies and/or clinical allergy to rabbits may have an increased risk for an allergic reaction. No other risk factors for allergic reactions to rhC1INH have been identified.
authors: Departments of Immunology, Dermatology and Rheumatology, University Medical Center Utrecht, PO Box 85090, 3508 AB, Utrecht, The Netherlands. C.E.Hack@umcutrecht.nl
authors: C Erik
authors: CE
authors: Hack
authors: Anurag
authors: A
authors: Relan
authors: Aartie
authors: A
authors: Baboeram
authors: Beatrijs
authors: B
authors: Oortwijn
authors: Serge
authors: S
authors: Versteeg
authors: Ronald
authors: R
authors: van Ree
authors: Rienk
authors: R
authors: Pijpstra
mesh_terms: D000707:Anaphylaxis / Q000139:chemically induced*; D054179:Angioedemas, Hereditary / Q000188:drug therapy*; D016022:Case-Control Studies; D050718:Complement C1 Inhibitor Protein / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D050718:Complement C1 Inhibitor Protein; D011994:Recombinant Proteins; D007073:Immunoglobulin E