원저 Lab Med Online Vol. 2, No. 3: 139-147, July 2012 진단면역학 최근 2 년간 Polycheck Allergy 검사결과의분석 : Skin Prick Test 및 과의비교 Analysis of Polycheck Allergy Results of the Recent Two Years: Comparison with Skin Prick Test and 정세리 1,4 * 장광천 2 * 조남준 3 한미순 1,4 김현숙 4 선제영 5 유종하 1,4 Seri Jeong, M.D. 1,4 *, Gwang-Cheon Jang, M.D. 2 *, Nam Joon Cho, M.D. 3, Mi Soon Han, M.D. 1,4, Hyon Suk Kim, M.D. 4, Je Young Sun 5, Jong-Ha Yoo, M.D 1,4 국민건강보험일산병원진단검사의학과 1 소아청소년과 2 피부과 3, 연세대학교의과대학진단검사의학교실 4, Department of Biochemistry and Cell Biology, Rice University 5 Departments of Laboratory Medicine 1, Pediatrics 2, and Dermatology 3, National Health Insurance Corporation Ilsan Hospital, Goyang; Departments of Laboratory Medicine 4, Yonsei University College of Medicine, Seoul, Korea; Department of Biochemistry and Cell Biology 5, Rice University, Houston, Texas, USA Background: Multiple Antigen Simultaneous Test (MAST)-immunoblot assay is a practical and economical test, which has been recently introduced nationwide. Authors investigated test efficiency of a MAST-immunoblot assay, Polycheck Allergy (PA). Methods: A total of 3,153 patients were tested by PA and the results were compared with the results of and skin prick test (SPT) in 532 and 75 patients, respectively. The correlation with the lge results measured by VIDAS was also analyzed. Results: The agreements of PA with SPT were 87.8% in the Inhalant Panel and 89.3% in the Food Panel and the agreement of with SPT was 95.2%. The most common allergens giving positive reactions were Dermatophagoides farinae (46.2%) and Dermatophagoides pteronyssinus (40.0%). SPT taken as a reference, PA compared with showed higher agreement (D. farinae, 76.0 vs. 70.7%; D. pteronyssinus, 76.0 vs. 74.4%), sensitivity (D. farinae, 72.7 vs. 68.2%; D. pteronyssinus, 75.0 vs. 71.2%) and specificity (D. farinae, 85.0 vs. 81.3%) except for the specificity for D. pteronyssinus (78.3 vs. 87.5%). The rate of allergen specific IgE positive patients was higher than that of negative patients when total IgE was over 100 ku/l. Conclusions: Our results showed that the agreement, sensitivity and specificity of PA were similar to or better than those of the previously established test,. The allergen specific IgE results of PA were in correlation with total IgE. PA may be used for testing allergen specific IgE to diagnose and treat allergic diseases. Key Words: Allergy, Polycheck Allergy,, Skin prick test, Allergen-specific IgE 서론 Corresponding author: Jong-Ha Yoo, M.D. Department of Laboratory Medicine, National Health Insurance Corporation Ilsan Hospital,1232 Baekseok-dong, Ilsandong-gu, Goyang 410-719, Korea Tel: +82-31-900-0909, Fax: +82-31-900-0925, E-mail: jhyoo92@empal.com Received: December 19, 2011 Revision received: March 27, 2012 Accepted: April 3, 2012 *These authors equally contributed to this work. This article is available from http://www.labmedonline.org 2012, Laboratory Medicine Online This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 주거환경과식습관의변화로천식, 알레르기비염, 아토피피부염, 음식및약품알레르기와같은질환이증가하고있다 [1-3]. 이러한알레르기질환의진단과치료에알레르기유발물질을규명하는것은필수적이다. 알레르겐을찾는검사로는피부단자시험이나알레르겐특이 IgE 검사가주로시행된다 [4]. 피부단자시험 (skin prick test) 은피부반응정도가혈청총 IgE 및특이 IgE값, 기관지유발시험과도높은일치율을보여임상에서널리이용되고있다 [5, 6]. 하지만피부반응성이떨어지는영아나노인, 항히스타민제나스테로이드제제의사용으로피부반응이감소한환자, 심한습진, 두드러기환자에게적용하기힘들며일중변동, 계절의변화, 검사받는부위에영향을받는다는한계가있다 [7, 8]. eissn 2093-6338 www.labmedonline.org 139
검사실에서는주로환자의혈청을이용한알레르겐특이 IgE 검사가주로시행되고있다. 1967 년 radioallergo sorbent test (RAST) 가개발되어쓰였으나개별항원마다검사를해야하는비경제성과고가의장비, 방사성동위원소취급의위험성이단점으로지적되어왔다 [9]. 이후 1985년알레르겐패널을이용하여다수의알레르겐을동시에검사할수있는 Multiple allergen simultaneous test chemiluminescent assay (MAST CLA) 가개발되어국내에서도널리사용되어왔다 [10, 11]. 여러연구에서 MAST CLA의검사결과를분석하였고주요항원에대한낮은민감도와비교적많은혈청을필요로한다는점, 오랜검사시간소요가문제점으로지적되었다 [12, 13]. 이를보완한 MAST-immunoblot 검사인 Polycheck Allergy (Biocheck GmbH, Munster, Germany) 가도입되었으나진단효능에대한국내보고가부족한상황이다. 따라서본연구는일산병원에내원한환자들을대상으로한 Polycheck Allergy (PA) 검사결과를기존의피부단자시험과 (Phadia AB, Uppsala, Sweden) 결과와비교하여그효용성을평가하고나아가임상의의적절한검사선택에도움이되고자하였다. 대상및방법 1. 대상 2009년 6월부터 2011년 5월까지국민건강보험일산병원진단검사의학과와소아청소년과, 피부과에피부단자시험, Polycheck Allergy, 알레르기검사가의뢰되었던환자를대상으로하였다. Polycheck Allergy 흡입형알레르기검사는 971건, 음식형알레르기검사는 2,182건, 검사는 583건, 피부단자시험은 83건이의뢰되었다. 의뢰된환자중 Polycheck Allergy 검사는남자 1,565 명, 여자 1,588명, 검사는남자 367명, 여자 215 명, 피부단자시험은남자 51명, 여자 32명이었다. 이들의연령분포는 0세부터 102세까지다양하였으나 과피부단자 시험은 20세이하에서의의뢰가대부분이었다 (Table 1). 검사결과비교시에는 Polycheck Allergy, 검사, 피부단자시험을동시에시행한환자를대상으로하였다. 과별로는 Polycheck Allergy 흡입형검사는이비인후과에서 (84.4%), 음식형검사는피부과에서 (95.3%), 검사와피부단자시험은소아청소년과에서 (96.9%, 100.0%) 주로의뢰되었다. 2. Polycheck Allergy 검사 Polycheck Allergy (Biocheck Corp., Munster, Germany) 키트를사용하여 Korea I-Standard와 Korea II-Inhalation는흡입형카세트로, Korea I-Standard와 Korea III-Food는음식형카세트로하여각각 40종의알레르겐에대해검사를시행하였다. 검사는제조사의설명서에근거하여시행하였다. 결과판독은 Biocheck Image Software (BIS) 를이용하여 class 0-6으로판독하였다. 3. 검사 (Phadia AB, Uppsala, Sweden) 키트를사용하여 114 종의알레르겐중임상적으로의심되는 6종의알레르겐에대해검사하였다. 250 사용설명서에근거하여시행하였으며결과는 class 0-6으로 7단계로분류하였고 0.35 kua/l 미만은음성으로판독하였다. 4. 피부단자시험환자의증상에따라의심되는알레르겐에대해검사하였으며 ATL 시약 (Bencard Corp, Brentford, UK) 를사용하여제조회사의지침대로시행하였다. 대상환자에서는 54종의알레르겐을검사하였다. 양성대조는 1% 히스타민, 음성대조는생리식염수를사용하였고 15분후팽진의가로, 세로직경과홍반의가로, 세로직경을재어크기가 3 mm 이상이거나양성대조군보다크면양성으로판정하였다. Table 1. Age and sex distribution of patients tested with Polycheck Allergy,, and skin prick test No. tested with Age Polycheck Allergy (yr) Inhalant panel Food panel Skin prick test Male Female Total (%) Male Female Total (%) Male Female Total (%) Male Female Total (%) 3 5 2 7 (0.7) 125 69 194 (8.9) 94 50 144 (24.7) 1 0 1 (1.2) 4-10 46 15 61 (6.3) 267 185 452 (20.7) 209 137 346 (59.3) 38 26 64 (77.1) 11-20 138 72 210 (21.6) 160 113 273 (12.5) 53 26 79 (13.6) 12 6 18 (21.7) 21-31 69 67 136 (14.0) 75 155 230 (10.5) 1 0 1 (0.2) 0 0 0 (0.0) 31-40 79 72 151 (15.6) 95 153 248 (11.4) 1 1 2 (0.3) 0 0 0 (0.0) 41-50 84 86 170 (17.5) 109 216 325 (14.9) 2 1 3 (0.5) 0 0 0 (0.0) 51-60 65 63 128 (13.2) 99 138 237 (10.9) 3 0 3 (0.5) 0 0 0 (0.0) >60 59 49 108 (11.1) 90 133 223 (10.2) 4 0 4 (0.9) 0 0 0 (0.0) Total 545 426 971 (100.0) 1,020 1,162 2,182 (100.0) 367 215 583 (100.0) 51 32 83 (100.0) 140 www.labmedonline.org
5. VIDAS 총 IgE 검사 VIDAS TOTAL IgE (Biomerieux SA., Marcy-l Etoile, France) 키트를사용하여특이 IgE 검사를시행한환자를대상으로검사하였다. 검사는제조사의사용설명서에근거하여시행하였다. 결과는 450 nm에서의형광강도를토대로총 IgE의농도를계산하였다. 6. 통계 Polycheck Allergy와, 피부단자시험각각의양성률과피부단자시험을기준으로한 Polycheck Allergy, 의일치율, 민감도, 특이도를 Microsoft사의 Excel (Microsoft Corp., Redmond, WA, USA) 를이용하여분석하였다. 양성률이높았던항원에대해서는 과피부단자시험을기준으로 Polycheck Allergy의일치율, 민감도, 특이도를각각구하였고 SPSS 프로그램 Version 12.0 (IBM Corp., New York, USA) 을이용하여일반선형모델 (general linear model, GLM) 로회귀분석하였다. VIDAS 의혈청총 IgE와 Polycheck Allergy의특이 IgE 결과비교는 Analyse-it 프로그램 Version 2.22 (Microsoft Corp., Redmond, WA, USA) 의 Pearson s chi-square test를사용하여통계학적으로검증하였다. 결과 1. 양성률 Polycheck Allergy를시행한 532명의환자 ( 동시시행 ) 중하나이상의항원에대해특이 IgE 항체가검출된경우는흡입형패널에서 359명 (67.5%), 음식형패널에서 180명 (33.8%) 이었다. 각알레르겐에따른양성률은흡입형에서는 house dust가 56.8%, Dermatophagoides farinae가 46.2%, Dermatophagoides pteronyssinus 가 40.0% 로높은비율을차지한반면음식형에서는 egg white (10.3%), soybean (10.2%), milk (9.2%) 가주요양성알레르겐이었다. 검사결과는 D. farinae (46.8%), D. pteronyssinus (44.8%), dog dander (9.1%) 가높은양성률을보였다. 피부단자시험의경우도 D. pteronyssinus (61.4%), D. farinae (60.2%), Dog hair (19.3%) 가주로검출되었다 (Table 2). 2. 일치율, 민감도및특이도 Polycheck Allergy,, 피부단자시험에공통적으로있는항원에대해피부단자시험을기준으로하여구한일치율은 Polycheck Allergy 흡입형이 74.7-96.0%, 음식형이 80.0-97.3% 였고 의경우는 19.5-100.0% 의분포를보였다. 민감도와특이도는모든항원을포함하여평균을구하였으며, Polycheck Allergy 흡입형은 33.6%, 음식형은 16.4%, 은 20.2% 의민감도를보였고 Polycheck Allergy 흡입형, 음식형, 의 Table 2. Positive rate of each allergen-specific IgE detected by Polycheck Allergy, skin prick test, and Allergen NCCLS code Polycheck Allergy (n=532) No. (%) of positive reaction in Skin prick test (n=83) (n=583) Dermatophagoides d1 213 (40.0) 51 (61.4) 260 (44.8) pteronyssinus* Dermatophagoides d2 246 (46.2) 50 (60.2) 272 (46.8) farinae* Cat dander* e1 73 (13.7) 16 (19.3) 23 (4.0) Dog dander* e5 125 (23.5) 53 (9.1) Egg white f1 55 (10.3) 6 (7.2) 50 (8.6) Milk f2 49 (9.2) 2 (2.4) 39 (6.7) Fish f3 7 (1.3) 2 (2.4) 2 (0.3) Wheat f4 16 (3.0) 2 (2.4) 10 (1.7) Rice f9 9 (1.7) 0 (0.0) Peanut f13 36 (6.8) 4 (4.8) 3 (0.5) Soybean f14 54 (10.2) 8 (9.6) 11 (1.9) Pork f26 24 (4.5) 3 (3.6) 0 (0.0) Common ragweed* w1 15 (2.8) 2 (2.4) 52 (9.0) Mugwort* w6 19 (3.6) 5 (6.0) 2 (0.3) Aspergillus fumigatus* m3 0 (0.0) 6 (7.2) 1 (0.2) Alternaria alternata* m6 28 (5.3) 8 (9.6) 36 (6.2) Cockroach* i6 28 (5.3) 2 (2.4) 11 (1.9) Dog hair e2 16 (19.3) Sheep epithelium e81 36 (6.8) 0 (0.0) Buckwheet f11 18 (3.4) 1 (1.2) 3 (0.5) Pea f12 1 (0.2) Hazel nut f17 1 (0.2) Almond f20 1 (0.2) Crab f23 28 (5.3) 5 (6.0) 0 (0.0) Shrimp f24 23 (4.3) 6 (7.2) 0 (0.0) Tomato f25 14 (2.6) 0 (0.0) Beef f27 28 (5.3) 3 (0.5) Potato f35 17 (3.2) 1 (0.2) Tuna f40 4 (0.8) 0 (0.0) Salmon f41 6 (1.1) 0 (0.0) Yeast f45 15 (2.8) 0 (0.0) 0 (0.0) Mackerel f60 7 (1.3) Cacao (chocolate) f93 8 (1.5) Peach f95 26 (4.9) 5 (6.0) Timothy Grass pollen* g6 18 (3.4) 3 (3.6) Rye pollen* g12 24 (4.5) House dust* h1 302 (56.8) 0 (0.0) Penicilium notatum m1 1 (1.2) 9 (1.5) Common silver birch* t3 54 (10.2) 9 (10.8) 1 (0.2) American beech t5 7 (8.4) 0 (0.0) Oak* t7 29 (5.5) 5 (6.0) 1 (0.2) White pine t16 7 (8.4) 0 (0.0) Japanese cedar t17 7 (8.4) 0 (0.0) Dermatomyces 9 (10.8) *Allergen in Polycheck Allergy Inhalant Panel; in Skin prick test; in Food Panel. www.labmedonline.org 141
Table 3. Agreement, sensitivity, and specificity of each multiple allergen simultaneous test compared with skin prick test as a reference Type of allergen Polycheck Allergy Agreement (%) Sensitivity Specificity Agreement (%) Sensitivity Specificity Dermatophagoides pteronyssinus* 76.0 75.0 (39/52) 78.3 (18/23) 74.4 71.2 (47/66) 87.5 (14/16) Dermatophagoides farinae* 76.0 72.7 (40/55) 85.0 (17/20) 70.7 68.2 (45/66) 81.3 (13/16) Cat dander* 74.7 11.1 (1/9) 93.3 (55/66) 91.5 0.0 (0/7) 100.0 (75/75) Egg white 90.7 37.5 (3/8) 97.0 (65/67) 91.5 0.0 (0/7) 100.0 (75/75) Milk 93.3 0.0 (0/3) 97.2 (70/72) 95.1 0.0 (0/4) 100.0 (78/78) Fish 97.3 - (0/0) 97.3 (73/75) 98.8 0.0 (0/1) 100.0 (81/81) Wheat 100.0 - (0/0) 100.0 (82/82) Peanut 85.3 11.1 (1/9) 95.5 (63/66) 98.8 0.0 (0/1) 100.0 (81/81) Soybean 80.0 10.0 (1/10) 90.8 (59/65) 96.3 0.0 (0/3) 100.0 (79/79) Pork 100.0 - (0/0) 100.0 (82/82) Common ragweed* 92.0 0.0 (0/4) 97.2 (69/71) 78.0 5.6 (1/18) 98.4 (63/64) Mugwort* 96.0 60.0 (3/5) 98.6 (69/70) 93.9 - (0/0) 93.9 (77/82) Aspergillus fumigatus* 93.3 - (0/0) 93.3 (70/75) 87.8 37.5 (3/8) 93.2 (69/74) Alternaria alternata* 86.7 0.0 (0/3) 90.3 (65/72) 97.6 0.0 (0/2) 100.0 (80/80) Cockroach* 94.7 0.0 (0/4) 100.0 (71/71) 100.0 - (0/0) 100.0 (82/82) Horse dander* 100.0 - (0/0) 100.0 (82/82) Rabbit epithelium* 100.0 - (0/0) 100.0 (82/82) Chicken feathers* 98.8 0.0 (0/1) 100.0 (81/81) Buckwheet 100.0 - (0/0) 100.0 (82/82) Crab 93.3 40.0 (2/5) 97.1 (68/70) 100.0 - (0/0) 98.8 (82/83) Shrimp 100.0 - (0/0) 100.0 (82/82) Yeast 100.0 - (0/0) 100.0 (82/82) Chicken meat 100.0 - (0/0) 100.0 (82/82) Bermuda grass* 98.8 - (0/0) 98.8 (81/82) Timothy Grass pollen* 93.3 25.0 (1/4) 97.2 (69/71) Meadow grass* 93.9 - (0/0) 93.9 (77/82) Penicilium notatum* 97.6 - (0/0) 97.6 (80/82) Cladosporium herbarum* 90.7 54.5 (6/11) 96.9 (62/64) 98.8 - (0/0) 98.8 (81/82) Mucor racemosus Candida albicans* 97.6 - (0/0) 97.6 (80/82) Ascaris Box-elder* 98.8 - (0/0) 98.8 (81/82) Grey alder* 95.1 - (0/0) 95.1 (78/82) Common silver birch* 90.7 54.5 (6/11) 96.9 (62/64) 91.5 100.0 (1/1) 91.4 (74/81) Hazel American beech* 91.5 - (0/0) 91.5 (75/82) Mountain juniper Oak* 89.3 16.7 (1/6) 95.7 (66/69) 93.9 0.0 (0/1) 95.1 (77/81) Maple leaf sycamore* 98.8 - (0/0) 98.8 (81/82) Willow* 96.3 - (0/0) 96.3 (79/82) White ash* 95.1 - (0/0) 95.1 (78/82) White pine* 92.7 - (0/0) 92.7 (76/82) Japanese cedar* 91.5 - (0/0) 91.5 (75/82) Marguerite* 98.8 - (0/0) 98.8 (81/82) Dandelion* 98.8 - (0/0) 98.8 (81/82) Goosefoot* 98.8 - (0/0) 98.8 (81/82) Citrus mix* 97.0 (64/66) Mean (%) 87.8/89.3 33.6/16.4 92.7/96.0 95.2 20.2 97.1 *Allergen in Polycheck Allergy Inhalant Panel; in Skin prick test; in Food Panel; Mean percentage of Polycheck Allergy Inhalant Panel/Food Panel. 142 www.labmedonline.org
특이도는각각 92.7%, 96.0%, 97.1% 의분포를나타내었다 (Table 3). 3. 주요항원에대한알레르겐특이 IgE 검출결과의비교 Polycheck Allergy와, 피부단자시험에서공통적으로높은양성률을보인 D. farinae, D. pteronyssinus 에대해 과피부단자시험을기준으로 Polycheck Allergy의결과를비교하여보았다. 두가지항원에대해 Polycheck Allergy와 을동시에검사한환자는 532명이었고 D. farinae 에대해서는일치율 87.4%, 민감도 86.9%, 특이도 87.8% 를보였고 D. pteronyssinus에대해서는일치율 87.6%, 민감도 90.1%, 특이도 85.9% 를나타내었다 (Table 4). 피부단자시험을기준으로는 75명의환자가 Polycheck Allergy 검사를같이하였고 D. farinae 의일치율, 민감도, 특이도는 76.0%, 72.7%, 85.0%, D. pteronyssinus 의경우는 76.0%, 75.0%, 78.3% 를보였다 (Table 5). 피부단자시험을기준으로 83명의환자가 검사를동시시행하였고 D. farinae의일치율, 민감도, 특이도는각각 70.7%, 68.2%, 81.3% 이었고, D. pteronyssinus 의경우는각각 74.4%, 71.2%, 87.5% 의결과를나타냈다 (Table 3). 두가지항원에대해 Polycheck Allergy의각 Table 4. Comparison of Polycheck Allergy with as a reference Dermatophagoides farinae Dermatophagoides pteronyssinus Positive (%) Negative (%) Total (%) Positive (%) Negative (%) Total (%) Polycheck Allergy Positive 213 (40.0) 35 (6.6) 248 (46.6) 191 (35.9) 45 (8.5) 236 (44.4) Negative 32 (6.0) 252 (47.4) 284 (53.4) 21 (3.9) 275 (51.7) 296 (55.6) Total 245 (46.1) 287 (53.9) 532 (100) 212 (39.8) 320 (60.2) 532 (100) Agreement Sensitivity Specificity Agreement Sensitivity Specificity 87.4% 86.9% 87.8% 87.6% 90.1% 85.9% Table 5. Comparison of Polycheck Allergy with skin prick test as a reference Dermatophagoides farinae Dermatophagoides pteronyssinus Skin prick test Skin prick test Positive (%) Negative (%) Total (%) Positive (%) Negative (%) Total (%) Polycheck Allergy Positive 40 (53.3) 3 (4.0) 43 (57.3) 39 (52.0) 5 (6.7) 44 (58.7) Negative 15 (20.0) 17 (22.7) 32 (42.7) 13 (17.3) 18 (24.0) 31 (41.3) Total 55 (73.3) 20 (26.7) 75 (100) 52 (69.3) 23 (30.7) 75 (100) Agreement Sensitivity Specificity Agreement Sensitivity Specificity 76.0% 72.7% 85.0% 76.0% 75.0% 78.3% 5 5 4 4 Polycheck Allergy (class) 3 2 Polycheck Allergy (class) 3 2 1 1 0 D. farinae 0 D. pterony 0 20 40 60 80 100 0 20 40 60 80 100 lmmunocap (kua/l) lmmunocap (kua/l) Fig. 1. Polycheck Allergy results plotted against results. Correlation coefficients (r 2 ) between and Polycheck Allergy for Dermatophagoides farina and Dermatophagoides pteronyssinus were 0.46 and 0.43, respectively (each, P<0.001). www.labmedonline.org 143
class에따른 의분포는 Fig. 1과같다. Polycheck Allergy (class) 와 (kua/l) 의결과를일반선형모델을통해회귀분석하였고 0.35 kua/l 미만이나 100 kua/l 이상의값을보고한결과는제외하였다. 두항원모두에서양의상관관계를보였으나 (P <0.001), r 2 값은 D. farinae 0.46, D. pteronyssinus 0.43으로낮았다. 상으로 VIDAS의혈청총 IgE를농도별로분류하여보았다 (level 1, 3.5-17.5 ku/l; level 2, 17.5-50 ku/l; level 3, 50-100 ku/l; level 4, >100 ku/l). 흡입형과음식형패널모두에서총 IgE가 100 ku/l 초과시 (level 4) 100 ku/l 이하보다특이 IgE 양성을보이는환자가음성을보이는환자보다통계학적으로유의하게 ( 흡입형 P<0.0001, 음식형 P = 0.0008) 높았다 (Table 6). 4. 동시양성항원수와평균양성항원수 Polycheck Allergy 검사시동시에양성을보인항원의개수별 분포를 Fig. 2 에나타내었다. 총 532 명의환자중 2 개이상의항원에 동시양성을보인환자는흡입형패널에서 359 명 (67.5%), 음식형패 널에서는 180 명 (33.8%) 였다. 흡입형패널에서는 3 개의항원에양성 을보인환자 (124 명 ) 가, 음식형패널에서는 1 개의항원에양성을보 인환자 (75 명 ) 가가장많았다. 평균양성항원수는 Polycheck Allergy 흡입형 2.2 개, 음식형 1.0 개, 1.5 개, 피부단자시 험 3.7 개로분석되었다. 5. VIDAS 에의한혈청총 IgE 결과의분포 No. (%) Polycheck Allergy 특이 IgE 에양성과음성인보인환자군을대 70 60 50 40 30 20 10 0 Inhalant panel Food panel 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 No. of specific IgE Fig. 2. Number of allergen-specific IgE detected simultaneously by Polycheck Allergy. The number of most frequently detected allergenspecific IgE was 3 (23.3%, 124/532) in inhalant panel and 1 (14.1%, 75/532) in food panel. 고찰 국내알레르기비염, 아토피피부염과같은알레르기질환의유병률은 2001년약 10% 에서 2011년 33% 정도로증가추세에있다 [2, 3]. 이에따라, 알레르기질환의진단과치료에중요한원인알레르겐을찾기위한검사법이개발되었고이에대한평가도시행되어왔다. 피부단자시험은 in vivo 검사로비만세포의탈과립과, IgE 항체로인한반응을보는것으로국내에서널리이용되고있는검사이며 [14], 표준화된참고방법이없는 in vitro 검사의평가기준으로사용되므로 [15, 16] 본연구에서도이를기준으로 Polycheck Allergy와 결과를비교하였다. 검사실검사로는화학면역발광법을이용하여혈청내알레르겐에특이 IgE를측정하는 MAST CLA가이용되어왔다 [17, 18]. 하지만주요알레르겐에대한낮은민감도, 긴검사소요시간 (5-6시간), 적은수의대조선 (2개), 검체량 (500 μl) 이상대적으로많음이문제점으로지적되었고이를보완한 MAST-immunoblot 법인 Polycheck Allergy가높은민감도, 적은소요시간 (3시간), 5개의 calibrator line, 적은검체량 (400 μl) 을장점으로최근국내에도입되어사용되고있다 [13, 19]. 비패널검사로서 114 종의항원중선택한항원에대해서만검사하는 은정량이가능하고환자와관계없는항원은검사하지않아도되는장점이있으나환자의증상만으로항원을선택하기에어려움이있다 [20]. 반면 Polycheck Allergy는패널검사로필요한항원이포함되지않는단점이있어정확하고빠른알레르기진단을위해각검사의의뢰양상과검사결과를비교, 파악하고적절성을평가할필요가있었다. 본연구에서는국내의다른보고와마찬가지로피부단자시험과두가지특이 IgE 검사에서 D. farinae와 D. pteronyssinus 가높은 Table 6. Distribution of serum total IgE levels determined by Polycheck Allergy in all allergen-specific IgE positive and negative patients Allergen-specific IgE 1 (3.5-17.5) Serum total IgE levels, class (ku/l) 2 (17.5-50.0) 3 (50.0-100.0) 4 (>100.0) Total (%) Inhalant Positive 27 (7.6%) 51 (14.4%) 48 (13.6%) 227 (64.3%) 353 (100.0) Negative 35 (21.0%) 41 (24.6%) 29 (17.4%) 62 (37.1%) 167 (100.0) Food Positive 13 (7.3%) 25 (14.0%) 23 (12.9%) 117 (65.7%) 178 (100.0) Negative 49 (14.3%) 67 (19.6%) 54 (15.8%) 172 (50.3%) 342 (100.0) 144 www.labmedonline.org
양성률을보였다 [19]. 특징적으로 house dust (56.8%) 가 Polycheck Allergy 흡입형패널에서가장높은양성률을보였는데항원간의빈도순서와양성률은보고논문마다약간의차이가있을수있다. 이의원인으로는대상군이일산병원내원환자중임상의의선택에의해결정되었다는점과검사방법에따른알레르겐의원료차이, 제조법차이등을들수있다. 또한, 지역과시대에따라원인알레르겐종류와양성률이다를수있다는점을생각해야한다. 마지막으로양성판정기준에따른보고차이를고려하여야한다. 과거논문에서는 class 2 이상을양성으로판정하여양성률이 30% 내외였다 [13, 21]. 하지만현재는환자가호소하는알레르기증상과의상관관계를고려하여 class 1도의미있는것으로보아이를양성기준으로판정하므로외국과비슷한높은양성률이보고되고있다 [12, 22]. 본연구에서도 class 1을양성판정기준으로하였고 67.5% 의양성률을보였다. 이는검사방법의차이는있지만같은기준을사용한 Lim 등 [12] 의양성률과유사하였다. 음식형패널에서는계란흰자, 콩, 우유순으로주요양성항원으로나타났고이는 Lim 등 [12] 이보고한결과와유사하지만빈도순서에서는약간의차이가있었다. 또한같은방법을사용한 Jang 등 [19] 의연구와비교시에는세가지항원모두높은양성률을보였는데이는본연구에서 3세미만의소아가많았기때문인것으로추정된다. 피부단자시험과의일치율은 Polycheck Allergy 흡입형, 음식형에서각각 87.8%, 89.3% 로 (95.2%) 보다약간낮은경향을보였다. 민감도는 Polycheck Allergy 흡입형 (33.6%) 이 (20.2%) 보다높았던반면특이도는 (97.1%) 이 Polycheck Allergy 흡입형 (92.7%) 과음식형 (96.0%) 보다높았다. 민감도와특이도가 0% 이거나 100% 인소수의항원을제외하더라도항원에따라민감도와특이도의차이가커서 Polycheck Allergy의흡입형민감도는 11.1-75.0%, 음식형은 10.0-40.0%, 은 5.6-71.2% 의분포를보였으며특이도는 78.3-98.6%, 90.8-97.3%, 81.3-98.8% 였다. 의경우 114 종의다양한항원을검사하므로항원에따른민감도와특이도의차이가커서평균수치의단순비교보다는알레르기질환의주요항원인 D. pteronyssinus 와 D. farinae 의결과를비교하는것이의미가있을것으로생각되었다. 피부단자시험을기준으로한 Polycheck Allergy의 D. pteronyssinus에대한일치율, 민감도, 특이도는각각 76.0%, 75.0%, 78.3% 였고 은각각 74.4%, 71.2%, 87.5% 로 Polycheck Allergy가일치율과민감도가높으며특이도는다소낮은것으로분석되었다. D. farinae의경우일치율과민감도, 특이도모두 보다 Polycheck Allergy가높은수치를나타내었다. 또한, 주요항원을대상으로 Polycheck Allergy 결과를, 피부단자시험을기준으로비교한결과일치율, 민감도, 특이도모두가피부단자시험보다는 의결과를더잘반영하는 것으로판단할수있었다. Polycheck Allergy 흡입형대상환자의절반이상이 2개이상의항원에동시양성을보였으며각각의알레르겐에노출되어생긴동시감작 (co-sensitization) 의영향도있지만한알레르겐에노출시비슷한구조를가진알레르겐사이의교차반응 (cross-reactivity) 의가능성도생각해볼수있었다 [23]. 평균양성항원수는 Polycheck Allergy 흡입형 (2.2개) 이가장높았고음식형 (1.0 개 ) 이가장낮았으며 (1.5 개 ) 의결과는두항원을모두포함하기때문인것으로추정되었다. 혈청총 IgE는소아에서흡연노출이나감염에의해서도증가되므로단독의결과로는알레르기질환을구분하기힘들다 [24, 25]. 하지만총 IgE는알레르기증상, 피부단자시험양성, 가족력과의통계학적연관성이밝혀져있어 [26] 주로특이 IgE 검사와동시에의뢰되어왔다. 본원진단검사의학과에서사용하고있는 VIDAS 총 IgE를 Polycheck Allergy의특이 IgE와비교한결과총 IgE가 100 ku/l 초과시 100 ku/l 이하의결과가나왔을때보다특이 IgE 양성을보이는환자가음성을보이는환자보다통계학적으로유의하게많음을확인할수있었다. 따라서총 IgE의수치가높은경우특이 IgE 검사를통해알레르기질환의원인을확인할필요가있다고생각되었다. 하지만특이 IgE가음성인환자에서도총 IgE가 100 ku/l을초과한경우가흡입형, 음식형패널에서각각 37.1%, 50.3% 로상당부분을차지하고있었다. 이의원인으로는검사패널내에원인알레르겐이포함되어있지않거나, 특이 IgE 항체역가가낮은경우가있어더욱다양한알레르겐에대한확인검사를하거나향후추적관찰이필요할것으로사료되었다 [27]. 결론적으로, Polycheck Allergy는, 피부단자시험과비교시간편하고경제적이며기존의검사 () 와비슷하거나높은일치도, 예민도, 특이도를보였다. 따라서임상적으로알레르기질환이의심되는환자나총 IgE가증가된환자에서효과적으로시행할수있는검사로판단된다. 요약 배경 : Multiple Antigen Simultaneous Test (MAST)-immunoblot assay는간편하고경제적인검사로최근국내에도입되었다. 저자들은 MAST-immunoblot assay (Polycheck Allergy; Biocheck GmbH, Germany) 의검사효용성을알아보고자하였다. 방법 : Polycheck Allergy가의뢰된 3,153 명의환자를대상으로분석을실시하여 (Pharmacia AB, Sweden), 피부단자시험결과와각각 532명및 75명의환자에서비교하였다. VIDAS (Biomerieux SA., France) 로측정한총 IgE 결과와의상관성도분석하였다. www.labmedonline.org 145
결과 : 피부단자시험과의일치율은 Polycheck Allergy 흡입형이 87.8%, 음식형이 89.3% 였고 은 95.2% 이었다. 양성률은 D. farinae (46.2%), D. pteronyssinus (40.0%) 가가장높은비율을차지하였으며두항원에대해피부단자시험을기준으로한일치율, 민감도, 특이도를조사한결과 Polycheck Allergy가 에비해 D. pteronyssinus 의특이도를제외하고는일치율 (D. farinae; 76.0 vs. 70.7%, D. pteronyssinus; 76.0 vs. 74.4%), 민감도 (D. farinae; 72.7 vs. 68.2%, D. pteronyssinus; 75.0 vs. 71.2%), 특이도 (D. farinae; 85.0 vs. 81.3%, D. pteronyssinus; 78.3 vs. 87.5%) 모두가높았다. 총 IgE는 100 ku/l 초과시특이 IgE 양성을보이는환자가음성을보이는환자보다유의하게많았다 ( 흡입형 P<0.0001, 음식형 P = 0.0008). 결론 : Polycheck Allergy는기존검사 () 와비슷하거나우수한일치율, 민감도, 특이도를보이고 VIDAS 총 IgE와도연관성을가지고있어알레르기질환의진단과치료에효과적으로사용될것으로판단하였다. 참고문헌 1. Min YG, Jung HW, Kim HS, Park SK, Yoo KY. Prevalence and risk factors for perennial allergic rhinitis in Korea: results of a nationwide survey. Clin Otolaryngol Allied Sci 1997;22:139-44. 2. Lee SI, Shin MH, Lee HB, Lee JS, Son BK, Koh YY, et al. Prevalences of symptoms of asthma and other allergic diseases in korean children: a nationwide questionnaire survey. J Korean Med Sci 2001;16:155-64. 3. Suh M, Kim HH, Sohn MH, Kim KE, Kim C, Shin DC. Prevalence of allergic diseases among Korean school-age children: a nationwide cross-sectional questionnaire study. J Korean Med Sci 2011;26:332-8. 4. Douglass JA and O Hehir RE. 1. Diagnosis, treatment and prevention of allergic disease: the basics. Med J Aust 2006;185:228-33. 5. Nelson HS. Diagnostic procedures in allergy. I. Allergy skin testing. Ann Allergy 1983;51:411-8. 6. Ownby DR. Allergy testing: in vivo versus in vitro. Pediatr Clin North Am 1988;35:995-1009. 7. Pipkorn U. Pharmacological influence of antiallergic medication on in vivo allergen testing. Allergy 1988;43:81-6. 8. Son BK and Lim DH. Allergic skin test. Korean J Pediatr 2007;50:409-15. 9. Wide L, Bennich H, Johansson SG. Diagnosis of allergy by an in-vitro test for allergen antibodies. Lancet 1967;2:1105-7. 10. Lim HS, Kim HS, Oh H. Current status of serum allergen tests in Korea. Korean J Lab Med 2008;28:124-9. 11. Brown CR, Higgins KW, Frazer K, Schoelz LK, Dyminski JW, Marinkovich VA, et al. Simultaneous determination of total IgE and allergen-specific IgE in serum by the MAST chemiluminescent assay system. Clin Chem 1985;31:1500-5. 12. Lim HS, Yoon JK, Lee HH. Allergen patterns using MAST CLA test in Korean pediatric patients. Korean J Clin Pathol 2001;21:292-7. 13. Yang SE, Oh HB, Hong SJ, Moon DH, Chi HS. Analysis of MAST chemiluminescent assay (MAST CLA) results performed in Asan Medical Center: Suggestion for the improvement of MAST CLA performance. Korean J Clin Pathol 1998;18:660-6. 14. Dreborg S. The skin prick test in the diagnosis of atopic allergy. J Am Acad Dermatol 1989;21:820-1. 15. Mosbech H, Nielsen NH, Dirksen A, Launbjerg J, Biering I, Søborg M. Comparison between specific IgE measured by RAST, two chemiluminescent assays and skin prick test. Allergol Immunopathol (Madr) 1992;20:220-4. 16. Eiken P, Mosbech H, Jacobsen L, Larsen P, Scharling B, Svendsen UG, et al. Comparison between two different assays for measurements of allergen-specific IgE and skin prick test in the diagnosis of insect venom allergy. Allergy 1992;47:495-7. 17. Scolozzi R, Boccafogli A, Vicentini L, Baraldi A, Bagni B. Correlation of MAST chemiluminescent assay (CLA) with RAST and skin prick tests for diagnosis of inhalant allergic disease. Ann Allergy 1989;62: 193a-b. 18. Lee S, Lim HS, Park J, Kim HS. A new automated multiple allergen simultaneous test-chemiluminescent assay (MAST-CLA) using an AP720S analyzer. Clin Chim Acta 2009;402:182-8. 19. Jang WR, Nahm CH, Kim JH, Lim DH, Jang TY, Moon YS, et al. Allergen specific IgE measurement with Polycheck Allergy: comparison of three multiple allergen simultaneous tests. Korean J Lab Med 2009;29: 465-72. 20. Contin-Bordes C, Petersen A, Chahine I, Boralevi F, Chahine H, Taïeb A, et al. Comparison of ADVIA Centaur and Pharmacia UniCAP tests in the diagnosis of food allergy in children with atopic dermatitis. Pediatr Allergy Immunol 2007;18:614-20. 21. Cha YJ, Chae SL, Park AJ. Evaluation of the MAST CLA assay system for measuring total IgE: Comparison with the pharmacia CAP system. Korean J Clin Pathol 1999;19:342-7. 22. Nepper-Christensen S, Backer V, DuBuske LM, Nolte H. In vitro diagnostic evaluation of patients with inhalant allergies: summary of probability outcomes comparing results of CLA- and CAP-specific immunoglobulin E test systems. Allergy Asthma Proc 2003;24:253-8. 23. Kim HS, Kim DJ, Lee SG. Analysis of simultaneous positivity to multi- 146 www.labmedonline.org
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