A combinatory approach of negative IgE to PVs and extracts allows stratifying the patients for tolerance-confirming FC with bony or cartilaginous fish
At last, the proportion of the patients who may tolerate specific fish was investigated, based on negative in vitro IgE tests to PV, RE and HE. Between 60% (Spain) and 90% (Luxembourg) of the patients were negative to ray PV, RE and HE (Figure 5A) . The percentage of the patients negative to each tested bony fish varied across the countries and up to 21% of the patients (mackerel, Denmark) were negative to one or more bony fish. For the cohorts from Austria, Denmark, Luxembourg and Norway, all tested species were found to be potentially tolerated by some patients. Only ray and herring were shown to be the potentially tolerated in the Chinese cohort, while for Spain, except for tuna, IgE tests to all other species were negative for some patients (Figure 5A ). All patients negative to PV, REs and HEs from specific species are listed in Table SIV . Based on these findings, 8 patients underwent prick-to-prick (PPT) with ray (Dipturus innominatus available in China), of which 6 showed skin reactivity neither to raw nor to cooked ray. These patients are candidates for future FCs to confirm their clinical tolerance. The patients with absence of reactivity to ray by PPT are labelled with an asterisk (*) in Table SIV .
Figure 5B shows the probability that all 3 IgE tests (to PV, RE and HE) are negative for species X (x-axis) if negative for species Y (y-axis). These data can be used to predict possible tolerance of specific species if tolerance of others is known. Negativity to tuna and mackerel showed the highest likelihood of negativity not only to ray but also to other bony fish. Specifically, patients negative to tuna have 92% probability to be negative to ray and swordfish. If negative to mackerel, 93% chance exists to be negative to herring and ray, and 86% to swordfish. However, if negative to salmon or swordfish, the probability of IgE tests to be negative to other bony fish is ≤58%.