Demographics of fish allergic participants
Sixty-seven and forty-six subjects fulfilling the inclusion criteria were recruited from the pediatric allergy clinics in HK and the Sagamihara National Hospital in Japan respectively (Table 1, Supplementary Tables E1, E2). The median (range) age of fish allergic subjects at evaluation was 6 (1-16) years and 10 (5-18) years for these two populations, respectively. The most common clinical features shared among the two populations were itchy mouth/throat (61.1%, 69/113) and urticaria (51.3%, 58/113) while subjects from HK also commonly displayed angioedema (59.7%, 40/67) upon fish ingestion (Supplementary Tables E1, E2). The two populations did not differ in terms of the symptom severity as reflected from oFASS (p = 0.5251). SPT to fish mix extract was only available for subjects recruited in HK with median (range) SPT wheal size of 5 (0-11) mm, and 48 subjects (84.2%) had positive SPT (cutoff at 3mm). The sIgE results for cod, tuna, salmon and grass carp are summarized in Table 1 and detailed in supplementary Tables E1 and E2. No difference was detected in sIgE levels to these fish species between the two populations, except for grass carp that HK subjects had significantly higher sIgE level comparing to Japanese subjects (Mann-Whitney test, p = 0.0020). Of note, 65/67 (97.0%) and 34/37 (91.8%) subjects from HK and Japan had positive sIgE to salmon (cutoff at 0.35kUA/L), of whom 72.3% and 70.6% had high sIgE level and above class III-VI, respectively. As for grass carp, 63/67 (95.5%) and 25/30 (83.3%) subjects from HK and Japan had positive sIgE, of whom 87.3% and 56.0% had high sIgE level and above class III-VI, respectively. An overall positive correlation between sIgE levels to salmon and grass carp was observed for both populations, by which a stronger correlation was found among the Japanese subjects (r = 0.69, p = 0.0002) than HK subjects (r = 0.33, p = 0.0061) based on Fisher r-to-z transformation (z = 2.01, p = 0.04). Sera of Japanese subjects yielded high sIgE response to salmon with an average grass carp/salmon sIgE ratio of 0.70 (0.02-1.93) while sera of HK subjects yielded higher sIgE response to grass carp with average ratio of 3.39 (0.02-20.8) (Supplementary Figure 1). Pairwise comparison between grass carp- and salmon-specific IgE levels also showed statistically higher grass carp-specific IgE level among HK subjects but statistically higher salmon-specific IgE level among Japanese subjects (Wilcoxon matched-pairs signed rank test, p = 0.0008 and 0.0315 respectively).