Sensitivity, specificity and positive predictive value of ALEX2 multiplex examination in patients suffering from atopic dermatitis and reaction to tomatoes

Figures & data

Table 1. Tomatoes allergenic molecules (Włodarczyk et al., 2022).

Molecular component	Biochemical name Protein family
Sola l 1	Profilin
Sola l 2	Beta-fructofuranosidase
Sola l 3	Non-specific lipid transfer protein type 1 (nsLTP1)
Sola l 4	Pathogenesis-related protein, PR-10, Bet v 1 family member, TSI-1
Sola l 5	Cyclophilin
Sola l 6	Non-specific lipid transfer protein type 2 (nsLTP2)
Sola l 7	Non-specific lipid transfer protein type 1 (nsLTP1)

Molecular component examined in ALEX2 Allergy Xplorer is shown extra bold.

Table 2. The level of specific IgE to Sola l and Sola l 6 in classes 0, 1, 2, 3, 4 in 100 AD patients (=100%).

	The number of patients (%) according to the level of specific IgE in classes 0–4 (100 patients included in the study = 100%)
	Class 0	Class 1	Class 2	Class 3	Class 4
Sola l	90.0%	6.0%	3.0%	1.0%	0.0%
Sola l 6	95.0%	1.0%	3.0%	1.0%	0.0%

Class 0 – negative (< 0.3 kU_A/L); Class 1 – low positivity (0.3–1 kU_A/L); Class 2 – moderate positivity (1–5 kU_A/L); Class 3 – high positivity (5–15 kUA/L); Class 4 – very high positivity (> 15 kU_A/L). The positive results of specific IgE to Sola l were confirmed in 10 patients (10%), low positivity was confirmed in 6 patients (6%), moderate positivity in 3 patients (3%) and high positivity in 1 patient (1%). The positive results of specific IgE to Sola l 6 were confirmed in 5 patients (5%), low positivity was confirmed in 1 patient (1%), moderate positivity in 3 patients (3%) and high positivity in 1 patient (1%).

Table 3. Sensitivity, specificity and positive predictive value of ALEX2 Allergy Xplorer.

Results of specific IgE	Number of patients – clinical reaction to tomatoes		p-value	Test characteristics	Rates and 95% confidence intervals
	Yes 15 (15%)	No 85 (85%)			Value	Lower	Upper
Sola l positive	1	9	1.000	Sensitivity	0.0667 (6.67%)	0.0017 (1.70%)	0.3195 (31.95%)
Sola l negative	14	76		Specificity	0.8941 (89.41%)	0.8085 (80.85%)	0.9504 (95.04%)
				Positive predictive value	0.1000 (10.0%)	0.0025 (0.25%)	0.4450 (44.5%)
Sola l 6 positive	1	4	0.564	Sensitivity	0.0667 (6.67%)	0.0017 (1.70%)	0.3195 (31.95%)
Sola l 6 negative	14	81		Specificity	0.9529 (95.29%)	0.8839 (88.39%)	0.9870 (98.70%)
				Positive predictive value	0.2000 (20.0%)	0.0051 (0.51%)	0.7164 (71.64%)
Complement to this table: area under the curve (AUC) for allergens Sola l and Sola l 6.
			Upper
Criterion	Count	AUC	Standard error	1-Sided	95% Confidence Limits
				P-Value	Lower	Upper
Sola_l	100	0.5184	0.0746	0.4024	0.3577	0.6493
Sola_l_6	100	0.4996	0.0374	0.5042	0.4229	0.5692

Definitions: Criterion is the Criterion Variable containing the scores of the individuals. Count is the number of the individuals used in the analysis. AUC is the area under the ROC curve using the empirical (trapezoidal) approach. Standard Error is the standard error of the AUC estimate. P-Value is the probability level to Test AUC > 0.5. The lower and upper confidence limits form the confidence interval for AUC.

Table 4. The significant relation (p-value <0.05) between the occurrence of clinical reactions to tomatoes, results of specific IgE to Sola l and Sola l 6 (sensitisation) and the results of specific IgE to other molecular components and allergens.

	Specific IgE to allergen Sola l and molecular component Sola l 6		Clinical reaction to tomatoes
	Sola l	Sola l 6 (nsLTP typ 2)
Specific IgE to allergens and molecular components of pollen, seeds, fruits and vegetables and latex
Hev b 1(Rubber Elongation Factor)
Hev b 3 (Small rubber particle proteins)
Hev b 5 (Acidic structural protein)
Hev b 6.02
Hev b 8 Profilin (actin-binding protein)
Hev b 11 (Chitinase class I)
Bet v 1 (PR 10 protein)
Api g 1 (PR-10 protein)
Api g 6 (Non-specific lipid transfer protein type 2)	<0.05	<0.05
Api g 2 (Non-specific lipid transfer protein, type 1)	<0.05	<0.05
Dau c (Carrot)
Dau c 1 (PR 10 protein)
Mal d 1 (PR 10 protein)			<0.05
Mal d 2 (Thaumatin-like protein)
Mal d 3 (Non-specific lipid transfer protein type 1)	<0.05	<0.05
Sol t (Potatoes)	<0.05
Phl p 1 (Beta-expansin)
Phl p 2 (Grass group II/III)
Phl p 5 (Timothy)
Phl p 6 (Timothy)
Secc pollen (Cultivated rye)
Pru p 3 (Non-specific lipid transfer protein)	<0.05	<0.05
Ara h 9 (Non-specific lipid transfer protein)	<0.05	<0.05
Jug r 3 (Non-specific lipid transfer protein)	<0.05	<0.05
Par j (Pellitory of the wall)
Art v 3 (Non-specific lipid transfer protein)	<0.05	<0.05
Cor a 9 (11S globulin)
Hel a (Sunflower)	<0.05

In patients with the positive results of specific IgE to Sola l and Sola l 6 (=sensitisation), we confirmed significantly higher sensitisation to molecular components Api g 2, Api g 6, Mal d 3, Pru p 3, Ara h 9, Jug r 3, Art v 3; in addition in patients with sensitisation to allergen extract Sola l, we confirmed significantly higher sensitisation to allergen extract Sol t (potatoes) and Hel a (Sunflower). The significant relation was confirmed between the results of specific IgE to Mal d 1 and patients with reaction to tomatoes.

Figure 1. The graph shows the significant relationship between the results of specific IgE to molecular allergen Sola l and the results of specific IgE to other molecular components. Values are the percentage of true positives (blue) and true negatives (orange) within Sola l.

Figure 2. The graph shows the significant relationship between the results of specific IgE to molecular component Sola l 6 and the results of specific IgE to other molecular components. Values are the percentage of true positives (blue) and true negatives (orange) within Sola l 6.

Figure 3. In patient with positive results of specific IgE to Sola l, we show the significant associations with other molecular components. Sensitivity vs 1-specificity plots – curves of parameters.

Figure 4. In patient with positive results of specific IgE to Sola l 6, we show the significant associations with other molecular components. Sensitivity vs 1-specificity plots – curves of parameters.

Table 5. In patients with positive results of specific IgE to Sola l, we show empirical AUC (area under the curve) with confidence intervals for each component with a significance level of the AUC = 0.5 test against the alternative that AUC > 0.5.

Upper
			Standard	1-Sided	95% Confidence limits
Criterion	Count	AUC	Error	P-Value	Lower	Upper
Api_g_2	100	0.7833	0.0763	0.0001	0.5829	0.8939
Api_g_6	100	0.7283	0.0917	0.0064	0.4947	0.8638
Mal_d_3	100	0.7300	0.0882	0.0046	0.5070	0.8614
Sol_t	100	0.7639	0.0866	0.0011	0.5357	0.8881
Pru_p_3	100	0.7322	0.0854	0.0033	0.5174	0.8602
Ara_h_9	100	0.8083	0.0834	0.0001	0.5719	0.9208
Jug_r_3	100	0.7772	0.0880	0.0008	0.5390	0.9003
Art_v_3	100	0.6711	0.1028	0.0480	0.4188	0.8272
Cor_a_9	100	0.6783	0.0911	0.0251	0.4584	0.8200
Hel_a	100	0.7472	0.0882	0.0025	0.5193	0.8759

AUC is the area under the ROC curve using the empirical (trapezoidal) approach. Standard error is the standard error of the AUC estimate. P-Value is the probability level to Test AUC > 0.5. The lower and upper confidence limits form the confidence interval for AUC.

Table 6. In patients with positive results of specific IgE to Sola l 6, we show empirical AUC (area under the curve) with confidence intervals for each component with a significance level of the AUC = 0.5 test against the alternative that AUC > 0.5.

Upper
			Standard	1-Sided	95% Confidence limits
Criterion	Count	AUC	Error	P-Value	Lower	Upper
Api_g_2	100	0.8158	0.1588	0.0234	0.2103	0.9689
Api_g_6	100	0.9389	0.0618	0.0000	0.6084	0.9919
Mal_d_3	100	0.8779	0.1045	0.0001	0.4407	0.9785
Pru_p_3	100	0.7832	0.1287	0.0139	0.3807	0.9362
Ara_h_9	100	0.7600	0.1409	0.0325	0.3295	0.9289
Jug_r_3	100	0.8758	0.1082	0.0003	0.4195	0.9788
Art_v_3	100	0.8147	0.1209	0.0046	0.4103	0.9514
Cor_a_9	100	0.7421	0.1388	0.0406	0.3360	0.9155

AUC is the area under the ROC curve using the empirical (trapezoidal) approach. Standard error is the standard error of the AUC estimate. P-Value is the probability level to Test AUC > 0.5. The lower and upper confidence limits form the confidence interval for AUC.

Table 7. The relation between the occurrence of clinical reaction to tomatoes, positive results of specific IgE to molecular components Sola l and Sola l 6 (sensitisation) and the severity of AD.

	Severity of atopic dermatitis – number of patients
	Mild	Moderate	Severe	Total
Clin. reaction +	2 (14.29%)	10 (16.39%)	3 (12.0%)	15 (15%)
Clin. reaction −	12 (85.71%)	51 (83.61%)	22 (88.0%)	85 (85%)
Total	14 (100%)	61 (100%)	25 (100%)	100 (100%)
p-Value	0.921
Sola l +	0 (0%)	7 (11.48%)	3 (12.0%)	10 (10%)
Sola l −	14 (100%)	54 (88.52%)	22 (88.0%)	90 (90%)
Total	14 (100%)	61 (100%)	25 (100%)	100 (100%)
p-Value	0.510
Sola l 6 +	0 (0%)	5 (8.2%)	0 (0%)	5 (5%)
Sola l 6 −	14 (100%)	56 (91.8%)	25 (100%)	95 (95%)
Total	14 (100%)	61 (100%)	25 (100%)	100 (100%)
p-Value	0.317

The association between the severity of AD and the clinical reaction to tomatoes and positive results of specific IgE to Sola l 6 and Sola l (sensitisation) was not confirmed. Sola l+: positive results of specific IgE, Sola l−: negative results of specific IgE, Sola l 6 +: positive results of specific IgE, Sola l 6 −: negative results of specific IgE.

Włodarczyk, K., Smolińska, B., & Majak, I. (2022 March 28). Tomato allergy: The characterization of the selected allergens and antioxidants of tomato (Solanum lycopersicum) – a review. Antioxidants (Basel), 11(4), 644. https://doi.org/10.3390/antiox11040644.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.