title: Sensitising effects of genetically modified enzymes used in flavour, fragrance, detergence and pharmaceutical production: cross-sectional study.
abstract: The use of genetically engineered enzymes in the synthesis of flavourings, fragrances and other applications has increased tremendously. There is, however, a paucity of data on sensitisation and/or allergy to the finished products. We aimed to review the use of genetically modified enzymes and the enormous challenges in human biomonitoring studies with suitable assays of specific IgE to a variety of modified enzyme proteins in occupational settings and measure specific IgE to modified enzymes in exposed workers.
  
  
  
  Specific IgE antibodies against workplace-specific individual enzymes were measured by the specific fluorescence enzyme-labelled immunoassay in 813 exposed workers seen in cross-sectional surveys.
  
  
  
  Twenty-three per cent of all exposed workers showed type I sensitisation with IgE antibodies directed against respective workplace-specific enzymes. The highest sensitisation frequencies observed were for workers exposed enzymes derived from α-amylase (44%), followed by stainzyme (41%), pancreatinin (35%), savinase (31%), papain (31%), ovozyme (28%), phytase (16%), trypsin (15%) and lipase (4%). The highest individual antibody levels (up to 110 kU/L) were detected in workers exposed to phytase, xylanase and glucanase. In a subgroup comprising 134 workers, detailed clinical diagnostics confirmed work-related symptoms. There was a strong correlation (r=0.75, p<0.0001) between the symptoms and antibody levels. Workers with work-related respiratory symptoms showed a higher prevalence for the presence of specific IgE antibodies against workplace-specific enzymes than asymptomatic exposed workers (likelihood ratio 2.32, sensitivity 0.92, specificity 0.6).
  
  
  
  Our data confirm the previous findings showing that genetically engineered enzymes are potent allergens eliciting immediate-type sensitisation. Owing to lack of commercial diagnostic tests, few of those exposed receive regular surveillance including biomonitoring with relevant specific IgE assays.
authors.affiliation: Occupational Toxicology and Immunology Unit, Institute for Occupational and Maritime Medicine (ZfAM), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|European Society for Environmental and Occupational Medicine, Berlin, Germany.
authors.forename: Lygia T
authors.initials: LT
authors.lastname: Budnik
authors.affiliation: Consultant on Occupational Lung Diseases and Allergy, Berlin, Germany.
authors.forename: Edwin
authors.initials: E
authors.lastname: Scheer
authors.affiliation: European Society for Environmental and Occupational Medicine, Berlin, Germany.|Occupational Lung Disease Unit, Birmingham Heartlands Hospital, Birmingham, UK.
authors.forename: P Sherwood
authors.initials: PS
authors.lastname: Burge
authors.affiliation: European Society for Environmental and Occupational Medicine, Berlin, Germany.|Occupational Lung Diseases and Allergy Unit, Charité Institute for Occupational Medicine (CIOM), Campus Benjamin Franklin, Charité-School of Medicine, Berlin, Germany.
authors.forename: Xaver
authors.initials: X
authors.lastname: Baur
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology; D003430:Cross-Sectional Studies; D003902:Detergents / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions; D004798:Enzymes / Q000009:adverse effects* / Q000276:immunology*; D005260:Female; D005421:Flavoring Agents / Q000009:adverse effects; D005818:Genetic Engineering; D005858:Germany; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology*; D007124:Immunoenzyme Techniques; D007073:Immunoglobulin E / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000276:immunology*; D016273:Occupational Exposure / Q000009:adverse effects* / Q000032:analysis; D004364:Pharmaceutical Preparations; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D000485:Allergens; D003902:Detergents; D004798:Enzymes; D005421:Flavoring Agents; D004364:Pharmaceutical Preparations; D007073:Immunoglobulin E
keywords: genetically modified enzymes; health risks; sensitization; specific IgE antibodies; type I allergy