# Kiwifruit Allergy--Molecular Basis, Diagnostics and Treatment
## 5 Cross-Reactivity of Kiwifruit Allergens  
Allergens originating from different species within the _Actinidia_ genus are obvious culprits in different cross-reactive reactions; for example, the clinical risk of reactions to allergens from golden and green kiwifruits is well established [6; 50]. However, a significant fraction of kiwifruit-allergic individuals also react to allergens originating from pollen (e.g., timothy grass or birth) or latex [73; 102]. In most of these cases, the reactions are caused by cross-reactivity, but co-sensitization cannot be excluded. Kiwifruit-allergic individuals who have pollinoisis most often react to different panallergens that originate from the PR-10, nsLTP, and profilin families. Cross-reactivity between Bet v 1 and both Act d 8 and Act c 8 is relatively common, as it was reported that almost 48% of Bet v 1-sensitized individuals react after eating kiwifruit [103]. The molecular basis of cross-reactivity between the PR-10 allergens was recently explained, and it was shown that PR-10 proteins from kiwifruit are very similar to their homolog from birch [65]. Similarly, cross-reactivity (or IgE co-recognition) between both Act d 10 and Act c 10, as well as different nsLTPs, was also reported [79]. Kiwifruit profilin, similarly to PR-10 and nsLTP allergens, often plays a role in PFAS [104]. Some kiwifruit allergens are also among molecules that are responsible for \"latex-fruit syndrome,\" which is an example of PFAS [1]. Not only panallergens originating from kiwifruit are implicated in cross-reactive reactions. Cross-reactivity has been demonstrated between actinidin (Act c 1 and Act d 1) and homologous proteins from fig, papaya, or wheat [86; 105; 106]. The cross-reactivity between Act d 1 and wheat was indicated in patients with baker's asthma who were also allergic to kiwifruit. It was suggested that the IgE co-recognition of actinidin and alpha-triticain was responsible for this condition (Figure 8) [86]. In the case of thaumatin-like protein (Act d 2 and Act c 2), cross-reactivity was reported with similar proteins originating from avocado, banana, and grape [50]. It was also reported that IgE levels toAct d 12 (11S globulin), but not Act d 13 (2S albumin), correlate positively with IgE levels to Ara h 3, suggesting cross-reactivity. This study was performed on a cohort of patients who were peanut-allergic, and 39% of these individuals were reported to have kiwifruit allergy as well [107]. Interestingly, the same study revealed the presence of kiwifruit 7S globulin that cross-reacted with Ara h 1, which implies the existence of a new unregistered kiwifruit allergen. The A-RISC index provides a method for the prediction of molecular and clinical cross-reactivity between allergens of the same family [23]. Use of the A-RISC index with kiwifruit and other fruit allergens allows for the prediction of other allergic responses that may arise as a result of sensitization to kiwifruit. For example, the comparison of allergens in the profilin family suggests a high likelihood of cross-reactivity between Act d 9 and all other profilin allergens, primarily to the profilins from pepper (Cap a 2) and potato  
Figure 8: Mapping of sequence conservation of wheat alpha-triticain on Act d 1 (actinidin) and sequence alignment. (**A**) SwissModel of mature Act d 1; ribbon representation is shown in two orientations related by 180\({}^{\circ}\) rotation. Conserved residues from wheat alpha-triticain are shown in dark blue. (**B**) Same as shown in (**A**), but as a surface representation. (**C**) Sequence alignment of mature Act d 1 (residues 127–380) and mature wheat alpha-triticain (residues 130–461), with conserved residues shown in dark blue. (Figure 5A). For allergies based on the thaumatin-like protein Act d 2, cross-reactivity may be expected if eating pepper, mango, and banana. The remaining families suggest a lower likelihood of cross-reactivity, although clinical cross-reactivity may differ from the predictions shown here.