Coping with cross-reactive carbohydrate determinants in allergy diagnosis

Introduction Te obvious purpose of any diagnostic measure is to obtain an accurate impression of the patient’s condition. In case of allergy diagnosis this entails the identifcation of the true culprit allergen while avoiding to indict harmless allergens. Among the various “mimickers of allergy” [1], protein-linked carbohydrates are a prominent and well defned cause of false-positive reactions. Te following chapters will deal with plant/insect fucose-contain- ing CCDs, how they became accepted as being clin- ically irrelevant, and how CCD-based false-positive results can be avoided. Finally, the possibly more serious role of α-1,3-galactose containing GalCDs will be discussed. History and structures of plant/insect CCDs More than 30 years ago, Aalberse and co-workers in- cubated patients’ sera with an unusual array of aller- gens and supposed allergens (e. g., potato and buck- wheat). Tey observed an almost ubiquitous cross- reactivity of some sera [2]. More precisely, these sera reacted with extracts from pollens, vegetable foods, and – noteworthy – also hymenoptera venoms. Te Coping with cross-reactive carbohydrate determinants in allergy diagnosis FRIEDRICH ALTMANN Department of Chemistry, University of Natural Resources and Life Sciences, Vienna, Austria Abstract A relevant proportion of allergy diagnosis is accom- plished by in vitro determination of specifc im- munglobulin E (sIgE) to extracts from suspected allergens. Such extracts inevitably contain glycopro- teins, which may react with patients’ IgE. In the case of plant and insect allergens, the relevant epitope structure is an α-1,3-fucose on the Asn-linked sugar residue of so-called N-glycans. Due to their wide distribution, N-glycans carrying this epitope are known as “cross-reactive carbohydrate determi- nant(s)” (CCD[s]). About 15 years of awareness al- low the conclusion that anti-CCD IgE does not cause noticeable clinical symptoms. In consequence, diagnostic results arising from CCD reactivity must be rated as false positives. With up to 30 % of CCD reactive patients, this can be regarded as a serious problem. Another cross-reactive carbohydrate determinant became notorious as a potential cause of anaphylac- tic reactions to a recombinant glycoprotein drug carrying α-1,3-galactose. Tis galactose-containing determinant (GalCD, galactose containing cross- reactive carbohydrate determinant) was supposed as a trigger for delayed allergic reactions to red meat in several cases. Tus, α-1,3-galactose may have clin- ical relevance in certain cases – possibly as a result of tick bites. Ofen, however, GalCDs probably cause false-positive results with milk and meat extracts. No clear evidence for the role of other non-human carbohydrate structures such as N-glycolylneur- aminic acid as CCD has been presented so far. Remedies for sIgE based in vitro diagnosis come in the of non-glycosylated recombinant aller- gen components or of specifc CCD inhibitors. Te high potential of recombinant