Comparison of ImmunoCAP™ and NOVEOS clinical performance
We performed ROC analysis to compare clinical performance of ImmunoCAP™
and NOVEOS. We also selected sIgE optimal thresholds allowing optimal
discrimination between food allergic and non-allergic individuals. As
presented in Table 2 and Figure S2, areas under ROC curves (AUC) were
comprised from 0.79 for hazelnut extract (ImmunoCAP™ f17) to 0.97 for
ovomucoid nGal d 1 (NOVEOS F233). However, the mean value of AUC was
higher for NOVEOS than for ImmunoCAP™ (p=0.03). Next, and for setting
the optimal threshold for the 10 food allergens, Youden’s index that
combines optimal sensitivity and specificity was calculated and the
optimal cut-off values for sIgE reported in Table 2. Cut-off values for
ImmunoCAP™ and NOVEOS were similar (mean: 6.7 ± 3.8
kUA/L for ImmunoCAP™ and 4.6 ± 2.1 kUA/L
for NOVEOS) and the difference was not significant. The most divergent
cut-off values were between hazelnut extract (ImmunoCAP™ cut-off 16.7
kUA/L versus NOVEOS cut-off 3.6 kUA/L)
and cow’s milk (ImmunoCAP™ cut-off 6.9 kUA/L versus
NOVEOS cut-off 3.3 kUA/L). Sensitivity, specificity,
positive (PPV) or negative (NPV) predictive values were also comparable
without significant difference (mean sensitivity and specificity: 81%
and 84% for ImmunoCAP™ and 84% and 86% for NOVEOS). The highest PPV
was 95% except for egg white extract (ImmunoCAP™ and NOVEOS: highest
PPV=90%) (Table 2). Next, sIgE cut-offs established for the 10 food
allergens were further used to discriminate allergic from non-allergic
individuals by calculating OR, RR, Cohen’s kappa coefficients, and
percentages of agreement between each method and patients’ status. As
presented in Figure 3, a strong association between sIgE results and
clinical status was reported for the 10 allergens. The overall values of
RR (4.1 for ImmunoCAP™ versus 4.6 for NOVEOS), OR, kappa and agreement
were higher for NOVEOS than for ImmunoCAP™ when data from all 10
allergens were pooled, as well as when only allergen extracts were
considered (Table S1). However, these differences were not significant.
For the four MA, OR and RR were higher for ImmunoCAP™ than for NOVEOS,
while agreement and kappa indexes were identical with both techniques
(Table S1). In addition, both techniques were associated with better OR,
RR, agreement and kappa indexes for MA than for allergen extracts (Table
S1). Considering individual allergens (Table S2), cow’s milk sIgE
results (extract and casein nBos d8) were associated with the highest RR
(8.2), OR (>100), percentages of agreement (90-92%) and
kappa indexes (0.80-0.83). The lowest values were obtained with
ImmunoCAP™ peanut extract (RR: 2.7; kappa: 0.49; agreement: 75%) and
hazelnut extract (RR: 2.6 for NOVEOS).
Cohen’s Kappa index showed a “good” (0.61-0.80) or “very good”
(0.81-1) degree of association for 6 out of 10 allergens tested for
ImmunoCAP™ as compared to 8/10 for NOVEOS (Table S2, p=0.035, Wilcoxon
test). In addition, percentages of agreement were above 80% for 9 out
of 10 allergens tested with NOVEOS while this was true for 7 out of 10
allergens tested with ImmunoCAP™ (Table S2). Overall, comparing kappa
indexes and agreement for 10 allergens (i.e. 20 comparisons),
values were more frequently higher for NOVEOS (11/20) than for
ImmunoCAP™ (2/20).
Finally, thirty-one non-allergic patients present with a class “1” or
class “2” sIgE results (0.35 to 3.5 kUA/L) with
ImmunoCAP™, but have a class “0” (≤0.35 kUA/L) NOVEOS
result (p<0.0001, Figure 2B), while there is no significant
difference between the two methods for allergic patients with low sIgE
results (Figure 2C).