한국 소아 밀 알레르기 환자에서 밀, 글루텐 및 오메가-5 글리아딘 특이 IgE 항체의 유용성

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: , . IgE , IgE . , , -5 IgE . : 18 , 2011 10 2015 3 , , -5 IgE 196 . 2 ‘ (wheat allergy, WA)’, ‘

(non-wheat allergy, Non-WA)’ , WA ‘ (wheat allergy

with anaphylaxis, WAAna_{)’ 2}

‘ (wheat allergy without anaphylaxis, WA

.

: 46 , WA 35

WAAna _{17 , WA}Non-Ana _{18 Non-WA 161 . WA}

Non-WA , , -5 IgE

(P<0.001).

optimal cutoff point , , , -5

IgE cutoff point 0.9 kUA/L 0.43 kUA/L, 0.19 kUA/L

-5 IgE IgE , IgE

(78%) (94%) . IgE

IgE -5

IgE WAAna _WANon-Ana _optimal

cutoff point 1.56 kUA/L ( 77%, 78%) . IgE (accuracy) , -5 IgE . : , , -5 IgE , -5 IgE .

v 1 4 A. 4 B. 5 6 15 19 20 ABSTRACT 25

Fig. 1. Receiver operating characteristic curves represent sensitivity and specificity of specific IgE to wheat (solid), gluten (dotted) -5 gliadin (dashed).

Table 1. Clinical characteristic of study subjects --- (7)

Table 2. IgE antibody levels to wheat, -5 gliadin, and gluten in subjects --- (10)

Table 3. Diagnostic performance of specific IgE to wheat, gluten and -5 gliadin at different cutoff points --- (11)

Table 4. Comparison of 3 diagnostic methods for clinical prediction of wheat allergy

I.

, , ,

, , , ,(Boyce et al., 2010;

Burks et al., 2012) , , , , , , ,

.(Kim et al., 2011; Ahn et al., 2012; et al., 2012) 70% 2014 1 33.6kg 1975 .(http://www.kofmia.org) , , 0.1-1.3%, 0-0.5%, 0.2-1.2% , 6 0.37% , 1

0.08% .(Zuidmeer et al., 2008; Kim et al., 2011; Lee et al., 2013a)

IgE IgE ,

IgE ,

, ,

(food-dependent exercise-induced anaphylaxis, FDEIA) .(Inomata, 2009)

IgE , IgE

.(Boyce et al., 2010) IgE

,

, .(Boyce et al., 2010)

IgE (positive decision point)

,

, (component-resolved diagnosis)

.(Sampson, 2001; Nilsson et al., 2015) (gluten) non-gluten

, 70% (gliadin)

(glutenin) .(Morita et al., 2009)

(wheat-dependent exercise-induced anaphylaxis, WDEIA) -5 ( -5 gliadin)

WDEIA .(Inomata, 2009; Morita

et al., 2009) -5

IgE

.(Beyer et al., 2008;

Ebisawa et al., 2012) -5

IgE (Lee et al., 2013b)

,

-5 IgE

II.

ImmunoCAP (Phadia, Uppsala, Sweden) , ,

. 2

, ‘

(wheat allergy, WA)’

‘ (non-wheat allergy, Non-WA)’ ,

. WA (Sampson

et al., 2006) ‘ (wheat allergy with anaphylaxis, WAAna_)’

2 ‘

(wheat allergy without anaphylaxis, WANon-Ana_{)’ .}

B.

IBM SPSS Statistics ver. 22.0 (IBM Co., Armonk, NY,

USA) t-test Mann-Whitney test .

Receiver Operating Characteristic (ROC) curve .

III.

Table 1. Clinical characteristic of study subjects WA Non-WA Total (n=35) WAAna (n=17) WANon-Ana (n=18) Total (n=161) Age (month)* 19 (9~91) † _{16 (9~87)} ‡ _{28 (9~91) 54 (4~214)} Sex (male/female) 25/10 13/4 12/6 84/77 Symptoms Eczema 19 9 10 52 Urticaria 35 17 18 139 Angioedema 13 9 4 9 Respiratory 17 16 1 19 Gastrointestinal 5 5 0 10

WA, wheat allergy

Non-WA, non-wheat allergy

WAAna_{, wheat allergy with anaphylaxis}

WANon-Ana_{, wheat allergy without anaphylaxis}

*_{Data are presented as median (25}th _{- 75}th_percentile) †_{P <0.001 vs. Non-WA}

‡_{P : not significant vs. WA}Non-Ana

P : not significant vs. Non-WA P : not significant vs. WANon-Ana

B. (WA) IgE

IgE , IgE , -5 IgE

WA 15.40 kUA/L, 22.80 kUA/L, 1.49 kUA/L , Non-WA

0.07 kUA/L, 0.03 kUA/L, 0.05 kUA/L WA Non-WA

(Table 2).

ImmunoCAP ROC curve

IgE AUC , IgE

0.976 (Fig.1A). Youden

optimal cutoff point

, IgE, IgE, -5 IgE

optimal cutoff point 0.90 kUA/L, 0.43 kUA/L, 0.19 kUA/L (Table 3).

WA Non-WA IgE

100% ,

-5 IgE 94%, 78% .

ImmunoCAP (assay cutoff point) 0.35 kUA/L

IgE , IgE , -5 IgE

100%, 100%, 71.4%, 80%, 86%, 97% .

95% ,

IgE , IgE , -5 IgE

3.12 kUA/L, 2.61 kUA/L, 0.21 kUA/L . 97%

IgE IgE 0.9

. -5 IgE 95%

0.06 kUA/L 89% .

C. (WAAna_{) (WA}Non-Ana₎

IgE

IgE , IgE , -5 IgE

WAAna _{15.40 kU} A/L, 22.80 kUA/L, 3.49 kUA/L WANon-Ana 13.35 kUA/L, 17.48 kUA/L, 0.34 kUA/L -5 IgE (Table 2). 0.35 kUA/L -5 IgE 100% 22% .

ImmunoCAP ROC curve , -5

IgE 0.743 AUC (Fig.1B). -5

IgE optimal cutoff point 1.56 kUA/L , ,

, , 77%, 78%, 77%, 78% (Table 3).

-5 IgE 6.92 kUA/L 83%

, 0.21 kUA/L 94%

Table 2. IgE antibody levels to wheat, -5 gliadin, and gluten in subjects IgE antibody level (kUA/L)

Wheat Gluten -5 Gliadin

WA (n=35) 15.40 (3.65~52.70) * 22.80 (4.32~64.90) † 1.49 (0.29~7.64) ‡ WAAna _{(n=17) 15.40 (9.97~51.70)}

22.80 (7.75~58.60) 3.49 (1.63~9.50) ¶ WANon-Ana _{(n=18) 13.35 (1.55~52.70) 17.48 (1.31~67.90) 0.34 (0.22~1.49)} Non-WA (n=161) 0.07 (0.05~0.17) 0.03 (0.01~0.09) 0.05 (0.05~0.05)

Data are presented as median (25th_{- 75}th_percentile)

WA, wheat allergy

Non-WA, non-wheat allergy

WAAna_{, wheat allergy with anaphylaxis}

WANon-Ana_{, wheat allergy without anaphylaxis} *, †, ‡_{P <0.001 vs. Non-WA}

P 0.409 vs. WANon-ana P 0.447 vs. WANon-ana ¶_{P 0.013 vs. WA}Non-ana

Table 3. Diagnostic performance of specific IgE to wheat, gluten and -5 gliadin at different cutoff points

WA vs. non-WA WAAna _{vs. WA}Non-Ana Specific IgE against Specific IgE against Wheat Gluten -Gliadin Wheat Gluten -Gliadin

AUC/ROC

0.969 0.976 0.925 0.583 0.577 0.743 P-value

<0.001 <0.001 <0.001 0.40 0.438 0.014 Assay cutoff point

Specific IgE (kUA/L) 0.35 0.35 0.35 0.35 0.35 0.35 Sensitivity, Specificity (%) 100, 80 100, 86 71, 97 100, 0 100, 0 100, 22

PPV, NPV (%) 52, 100 60, 100 83, 94 49, 0 49, 0 94, 50 Optimal cutoff point

Specific IgE (kUA/L) 0.90 0.43 0.19 3.05 2.85 1.56 Sensitivity, Specificity (%) 97, 89 100, 88 89, 94 94, 39 100, 39 77, 78

PPV, NPV (%) 66, 99 64, 100 78, 97 59, 88 61, 100 77, 78 Positive decision point 1) 95% specificity 2) 83% specificity

Specific IgE (kUA/L) 3.12 2.61 0.21 73.5 87.6 6.92 Sensitivity, Specificity (%) 77, 95 83, 95 86, 95 24, 83 12, 83 41, 83

PPV, NPV (%) 77, 95 78, 96 79, 97 57, 54 40, 50 70, 60 Negative decision point 1) 97% sensitivity 2) 94% sensitivity

Specific IgE (kUA/L) 0.90 0.54 - 2.40 3.64 0.21 Sensitivity, Specificity (%) 97, 89 97, 89 - 94, 33 94, 39 94, 22

PPV, NPV (%) 66, 99 66, 99 - 57, 86 59, 88 53, 80

WA, wheat allergy; Non-WA, non-wheat allergy; WAAna_{, wheat allergy with anaphylaxis;}

WANon-Ana_{, wheat allergy without anaphylaxis ; AUC, area under the curve; ROC,}

receiver operating characteristic; PPV, positive predictive value; NPV, negative predictive value

(A)

(B)

Fig.1 Receiver operating characteristic curves represent sensitivity and specificity of specific IgE to wheat (solid), gluten (dotted) -5 gliadin (dashed). (A) WA vs.

Non-WA, (B) WAAna _{vs. WA}Non-Ana_{. The numbers in parentheses indicate AUC}

values ;WA, wheat allergy ; Non-WA, non-wheat allergy ; WAAna_{, wheat allergy with}

D. IgE

(accuracy)

, IgE, IgE, -5 IgE

91.8%, 92.9%, 93.4% . IgE IgE 93.4% , 91.3% . IgE -5 IgE IgE -5 IgE 93.9% , 91.3%, 92.3% . IgE , , ,

93.9%, 91.8%, 90.8% (Table 4). WAAna _WANon-Ana _-5

IgE .

Table 4. Comparison of 3 diagnostic methods for clinical prediction of wheat allergy Diagnostic method Positive decision point

(kUA/L) Sensitivity (%) Specificity (%) Accuracy (%) 1 component Wheat* 0.90 kUA/L 77 95 91.8 Gluten† 0.43kUA/L 83 95 92.9 -Gliadin ‡ 0.19 kUA/L 86 95 93.4 2 components Wheat, Gluten And 77 97 93.4 Or 83 93 91.3 Wheat, -Gliadin And 74 98 93.9 Or 89 92 91.3 Gluten, -Gliadin And 80 97 93.9 Or 89 93 92.3 3 components Wheat, Gluten, -Gliadin 3 positive 74 98 93.9 2 positive 83 94 91.8 1 positive 89 91 90.8

IV.

.(Sampson, 2001; Perry et al., 2004; Pourpak et al., 2004; Keet et al., 2009; Canonica et al., 2013) IgE ,

IgE , -5 IgE

.

IgE ROC curve WA

Non-WA IgE , IgE , -5

IgE AUC 0.969, 0.976, 0.925 ,

(P<0.001). assay cutoff point (0.35

kUA/L) IgE , IgE

52% 60% , -5

al., 2015) IgE 52%, -5 IgE 80% . Sampson (Sampson, 2001) IgE 26 kUA/L, 74% , 26 kUA/L 91% . , , , , .

optimal cutoff point

IgE IgE cutoff point

0.9 kUA/L 0.43 kUA/L , -5 IgE 0.19

kUA/L assay cutoff point 0.35 kUA/L .

-5 IgE IgE , IgE

(78%) , (94%) . 95% IgE , IgE , -5 IgE 77%, 78%, 79% , 97% IgE IgE 99% . -5 IgE 95% . IgE cutoff point

.(Palosuo et al., 2001; Shibata et al., 2011; Makela et al., 2014; Nilsson et al., 2015) IgE , IgE , IgE 0.9 - 3.12 kUA/L, 0.54 - 2.61 kUA/L . Non-WA 161 3 IgE 20.5 kUA/L, 27.1 kUA/L, 46.2 kUA/L . IgE . -5 IgE 95% .

Sampson (Sampson and Ho, 1997) , ,

IgE IgE

.

IgE -5 IgE WAAna _WANon-Ana

,

.(Beyer et al., 2008; Ito et al., 2008; Ebisawa et al., 2012; Makela et al.,

2014; Nilsson et al., 2015) -5

IgE optimal cutoff point 1.56 kUA/L ( 77%, 78%)

, -5

. IgE . (accuracy) , IgE 91% -5 IgE , . , -5 IgE . , IgE , IgE -5 IgE , optimal cutoff point IgE , -5 IgE .

V.

, , -5 IgE

,

-5 IgE

1. , , , , , , , , , :

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Abstract

-Usefulness of specific IgE antibody levels to wheat, gluten and -5

gliadin for wheat allergy in Korean children

Jongseo Yoon

Department of Medical Science The Graduate School, Ajou University

(Supervised by Associate Professor Sooyoung Lee)

Purpose: The aim of this study was to assess the clinical usefulness and added diagnostic

value of specific IgE antibodies to wheat, gluten and -5 gliadin in diagnosing wheat allergy and distinguishing wheat anaphylaxis.

Methods: This study included 196 children who visited Ajou University Hospital for suspicious food allergy. The subjects were divided into two groups; wheat allergy (WA) group and non-wheat allergy (Non-WA) group. The patients with wheat allergy were further divided into two groups according to their symptoms: wheat allergy with anaphylaxis (WAAna_{) group and wheat allergy without anaphylaxis (WA}Non-Ana_{) group. The}

serum concentrations of total IgE and specific IgE antibodies to wheat, gluten and -5 gliadin were measured.

were significantly higher in WA group compared to those in Non-WA group and the positive decision points (specificity of 95%) were 3.12 kUA/L, 2.61 kUA/L, and 0.21

kUA/L respectively. The combination of specific IgE antibodies to wheat and -5 gliadin

resulted in the highest accuracy of 93.9% in diagnosing wheat allergy. In differentiating WAAna _{group from WA}Non-Ana _{group, only the specific IgE antibodies to -5 gliadin}

showed significant difference at the optimal cutoff point of 1.56 kUA/L.

Conclusion: Our results show that the individual levels of specific IgE antibodies to

wheat, gluten or -5 gliadin had considerably high accuracies in diagnosing wheat allergy, and specific IgE antibody to -5 gliadin was particularly useful in predicting wheat anaphylaxis.