대한진단검사의학회지 : 제 25 권제 6 호 2005 Korean J Lab Med 2005; 25: 진단면역학 MAST CLA 알레르기검사에서동시양성알레르겐의분석 김현수 김대중 이성규 분당제생병원진단검사의학과 Analysis of Simultaneous

대한진단검사의학회지 : 제 25 권제 6 호 2005 Korean J Lab Med 2005; 25: 448-56 진단면역학 MAST CLA 알레르기검사에서동시양성알레르겐의분석 김현수 김대중 이성규 분당제생병원진단검사의학과 Analysis of Simultaneous Positivity to Multiple Allergens on MAST CLA Test Hyun Soo Kim, M.D., Dai Joong Kim, M.T., and Seong Gyu Lee, M.D. Department of Laboratory Medicine, Bundang Jesaeng General Hospital, Sungnam, Korea Background : Allergic patients showing a simultaneously positive reaction to multiple allergens are frequently found. The purpose of this study was to analyze the pattern of simultaneously positive results to the allergens of MAST CLA Korean inhalant and food panels. Methods : From March 2004 to March 2005, we analyzed the results of the MAST CLA allergy test performed at Bundang Jesaeng General Hospital. During this period, 1,421 inhalant panels and 331 food panels were tested. Results : Mite-farinae (40.3%) and mite-pterony (34.8%) specific IgE were the most frequently detected in the inhalant panel and also in the food panel. Simultaneously positive rates to two or more allergens were 41.9% (595/1421) in the inhalant panel and 32.3% (107/331) in the food panel. Allergens with a highly positive rate (Mite-f, Mite-p, house dust) were frequently detected simultaneously with other allergens, and allergens known to have cross-reactivity showed simultaneously positive results among themselves (i.e. among various pollen allergens; among allergens associated with the pollen-food syndrome; among grain allergens; among milk and cheese; among fungi allergens; among house dust mites and house dust; among cockroach, crab and shrimp; and among cat and dog). Conclusions : Simultaneous positivity on the MAST CLA allergy test can be found frequently among various allergens, especially allergens with cross-reactivity. More advanced techniques using recombinant allergens may be needed for further analysis of this finding. (Korean J Lab Med 2005; 25: 448-56) Key Words : Allergy, MAST CLA, Specific IgE, Simultaneous positivity, Cross-reactivity 서 최근 20-30년사이에전세계적으로알레르기환자가급격히증가되었다. 알레르기가의심되는환자에서알레르기유발물질 ( 알레르겐 ) 을규명하는것은환자의진단에중요할뿐만아니라원인항원의회피나면역치료등환자의치료에이용되므로그중요성이점차강조되고있다. 알레르겐을규명하는데환자의병력 접수 : 2005 년 9 월 29 일접수번호 : KJLM1888 수정본접수 : 2005 년 11 월 10 일교신저자 : 김현수우 463-774 경기도성남시분당구서현동 255-2 분당제생병원진단검사의학과전화 : 031-779-0242, Fax: 031-779-0257 E-mail: hskim@dmc.or.kr 론 이매우중요하며, 알레르겐유발시험이가장확실한방법이나시행하기어려우므로, 피부단자시험이나알레르겐특이 IgE 항체검사가주로사용된다. 그러나아직까지피부단자시험, 알레르겐특이 IgE 항체검사, 알레르겐유발시험등의검사방법들에대한표준화가이루어지지않았고, 원인항원의종류도수백종류에이르며 (http://www.allergen.org), 계속해서새로운알레르겐이밝혀지고있으므로, 알레르기환자에서원인이되는알레르겐을증명하는것이쉽지않다. 또한피부단자시험이나알레르겐특이 IgE 검사의결과가환자의증상과불일치하는경우가많으므로결과해석시주의해야한다. 이전에는검사실에서이용되는알레르겐특이 IgE 검사가 1-2 종류밖에없었으나최근여러가지검사방법들이개발되었다. 국 448

MAST CLA 알레르기검사에서동시양성알레르겐의분석 449 내에서많이사용되고있는알레르겐특이 IgE 검사를크게두분류로나누면 RAST, UniCAP과같이알레르겐을한종류씩선택하여검사하는방법과, MAST CLA와같이수십종의알레르겐이부착되어있는상품화된패널을이용하는방법이있다. 알레르겐을한종류씩선택하여검사하는방법은정량이가능하고환자와관계없는불필요한항원에대한검사를할필요가없는장점이있으나, 알려진알레르겐의종류가너무많으므로환자의증상만듣고어떤항원을선택하여검사를낼것인지판단하기가쉽지않다. 반면패널을이용하는검사법은패널이한정되어있으므로검사할항원의선택이용이한반면, 불필요한항원이검사패널에포함되어있는경우가흔하다. 그러므로검사실에서는알레르기를진단하는여러가지검사방법중어떤방법을선택할지또한검사실에서사용하고있는검사방법이적절한지를평가할필요가있다. 또한알레르기를일으키는원인항원은지역별로그분포가다르며주위환경의변화와함께지속적으로변화하고있으므로알레르기를일으키는원인항원의지역별규명이필요하고각검사실에서는사용하고있는알레르기검사의항원이그지역에맞는항원의조합인지확인할필요가있다. 본연구에서사용된 MAST CLA 검사는 35종의항원에대한특이 IgE 항체를검사할수있으며 1990년대초반에국내에도입되어패널검사로는현재까지가장널리사용되고있는검사법으로, 한국형패널로개발된이후두차례항원조합을변경시켜왔다. 알레르기환자는 2종류이상의항원에대해알레르기를가지고있는경우가많은데 MAST CLA 검사를하다보면여러알레르겐에동시양성인환자가흔히발견된다. MAST CLA 검사로수행한각항원의양성률에관한여러보고 [1-7] 가있으나 MAST CLA 검사패널내에서동시에잘나타나는항원의조합에대해서는거의알려진바가없다. 그러므로저자들은 13개월간분당제생병원에서시행된 MAST CLA 검사결과를분석하여분당, 성남지역의환자가많은분당제생병원에서흔히나타나는알레르기항원을규명하고, MAST CLA 한국형패널내에서동시양성항원의양상을파악하고자하였다. 1. 대상 대상및방법 2004년 3월부터 2005년 3월까지 13개월동안분당제생병원진단검사의학과에 MAST CLA 알레르기검사가의뢰되었던환자 를대상으로하였다. 이기간동안흡입형알레르기검사가총 1,421 건이의뢰되었고음식형알레르기검사가총 331건이의뢰되었다. 의뢰된환자중남자가 942명, 여자가 810명이었으며, 연령분포는 0세부터 93세까지다양하였으나흡입형, 음식형모두 10세이하에서의뢰가많았다 (Table 1). 과별로는흡입형알레르기검사는이비인후과에서대부분의뢰되었으며 (87.3%), 음식형알레르기검사는피부과 (58.9%) 와소아과 (32.6%) 에서주로의뢰되었다 (Table 2). 2. MAST 검사방법 MAST CLA Allergy test (Hitachi Chemical Diagnostics, Inc, CA, USA) 를사용하여검사하였다. MASTpette 는음식형패널 (Food panel) 과흡입형패널 (Inhalant panel) 의 2종류가 Table 2. Departmental distribution of patients tested with MAST CLA Department No. (%) tested inhalant panel No. (%) tested food panel OL 1240 (87.3) 2 (0.6) DM 4 (0.3) 195 (58.9) PD 75 (5.3) 108 (32.6) IMP 25 (1.8) 14 (4.2) OT 25 (1.8) 3 (0.9) Others 52 (3.7) 9 (2.7) Total 1421 (100) 331 (100) Abbreviations : OL, department of otolaryngology; DM, department of dermatology; PD, department of Pediatrics; IMP, department of pulmonology; OT, department of opthalmology, Others: departments of chest surgery, emergency medicine, family medicine, general surgery, cardiology, endocrinology, gastroenterology, nephrology, neurology, neurosurgery, orthopedic surgery, plastic surgery, psychology, rheumatology, rehabilitation medicine, urology. Table 1. Age and sex distribution of patients tested with MAST CLA Age (years) No. tested with inhalant panel Male Female Total (%) No. tested with food panel Male Female Total (%) 10 242 152 394 (27.7) 62 65 127 (38.4) 11-20 158 88 246 (17.3) 15 15 30 (9.1) 21-30 93 81 174 (12.2) 19 17 36 (10.9) 31-40 113 106 219 (15.4) 23 33 56 (16.9) 41-50 89 91 180 (12.7) 15 21 36 (10.9) 51-60 42 73 115 (8.1) 14 15 29 (8.8) >60 49 44 93 (6.5) 8 9 17 (5.1) Total 786 635 1,421 (100) 156 175 331 (100)

450 김현수 김대중 이성규 있으며각각의항원구성은 Table 3과같다. MASTpette 라는 chamber 내에는 38개의셀룰로스실이사다리모양으로배열되어 Table 3. Positive rate of each allergen-specific IgE detected by MAST CLA Allergen NCCLS code No. (%) Positive Inhalant panel Food panel Food Baker s yeast f45 3 (0.9) Barley f6 9 (2.7) Beef f27 3 (0.9) Cheese f81 16 (4.8) Chicken f83 5 (1.5) Citrus mix f33, f208, f306 10 (3.0) Codfish f3 7 (2.1) Crab f23 34 (2.4) 8 (2.4) Egg white f1 25 (1.8) 24 (7.3) Garlic f47 9 (2.7) Milk f2 36 (2.5) 22 (6.6) Onion mix f48 10 (3.0) Peach f95 37 (2.7) 14 (4.2) Peanut f13 19 (5.7) Pork f26 2 (0.6) Rice f9 11 (3.3) Salmon f41 2 (0.6) Shrimp f24 57 (4.0) 16 (4.8) Soybean f14 29 (2.0) 16 (4.8) Tuna f40 5 (1.5) Wheat f4 16 (4.8) Tree Acacia t19 31 (2.2) Ash mix t33, t15, t3 36 (2.5) Birch/alder t2, t3 54 (3.8) 13 (3.9) Black willow t32 28 (2.0) Cedar, Japan t17 21 (1.5) Hazelnut t4 47 (3.3) Poplar mix t14 30 (2.1) Sycamore mix t11 24 (1.7) White oak t7 128 (9.0) 28 (8.5) Grass Bermuda grass g2 73 (5.1) Orchard grass g3 65 (4.6) Rye g12 75 (5.3) 25 (7.6) Timothy grass g6 69 (4.9) Weed Dandelion w8 50 (3.5) Goldenrod w12 48 (3.4) Mugwort w6 70 (4.9) 24 (7.3) Pigweed mix w14, w82 28 (2.0) Russian thistle w11 66 (4.6) Short ragweed w1 107 (7.5) 23 (6.9) Mold Alternaria m6 66 (4.6) 10 (3.0) Aspergillius m3 164 (11.5) 19 (5.7) Cladosporium m2 36 (2.5) 8 (2.4) Pencillium m1 53 (3.7) Epithelium Cat e1 117 (8.2) 18 (5.4) Dog e5 165 (11.6) 22 (6.6) Insect Cockroach i6 139 (9.8) 25 (7.6) House dust House dust h2 298 (21.0) 36 (10.9) Mite Mite-farinae d2 573 (40.3) 99 (29.9) Mite-pterony d1 495 (34.8) 72 (21.8) Total 1,421 (100) 331 (100) 있는데첫째줄은양성대조, 둘째줄은음성대조, 셋째줄은항-IgE 가부착되어있고, 4째줄부터 38번째줄까지 35종의알레르겐이부착되어있다. 검사방법은제조회사의지침대로시행하였는데요약하면다음과같다. Chamber에환자혈청을넣고 18시간동안실온에서반응시킨후세척용완충액으로 3회세척하였다. 효소표지항-IgE 항체용액을 chamber에넣고실온에서 4시간반응시킨후 3회세척하고발광시약을다시 chamber에넣고실온에서 30분반응시켰다. 결과는 MAST CLA-1 luminometer를이용하여 class 0, 1/0, 1, 2, 3, 4의 6단계로판독되며 class 1 이상을양성으로판정하였다. 3. 결과분석 MAST CLA-1 luminometer의결과는검사실정보시스템으로전송되므로 13개월동안의 MAST 검사결과를 Microsoft사의 Excel (Microsoft corporation, Redmond, WA, USA) 을이용하여각항목을분석하였다. 결과 1. 각항원양성률흡입형알레르기항원으로는 mite-farinae (Dermatophagoides farinae) 와 mite-pterony (Dermatophagoides pteronyssinus) 가각각 40.3%, 34.8% 로가장양성률이높았고 house dust (21.0%), dog (11.6%), aspergillus (11.5%), cockroach (9.8%), white oak (9.0%), cat (8.2%), short ragweed (7.5%), rye (5.3%), Bermuda grass (5.1%) 가 5% 이상의양성률을보였다 (Table 3). 음식형알레르기패널에는흡입형알레르기패널에없는음식항원 15개가추가되었었는데이중 10% 를넘은것은없었고 egg white (7.3%), milk (6.6%), peanut (5.7%) 이 5% 이상의양성률을나타내었다. 2. 동시양성항원수음식형또는흡입형패널의각각 35개의항원중동시에양성으로나타난항원의개수별분포를 Table 4에나타내었다. 흡입형알레르기검사가의뢰된 1,421검체중 2개이상의항원에동시양성을보인것이 595검체 (41.9%) 였고음식형알레르기검사는 331검체중 107검체 (32.3%) 에서 2개이상의항원에동시양성을보였다 (Table 4). 3. 연령별양성률및평균양성항원수흡입형과음식형알레르기검사의연령별양성률과평균양성항

MAST CLA 알레르기검사에서동시양성알레르겐의분석 451 Table 4. Number of allergen-specific IgE detected simultaneously by MAST-CLA No. of positive specific IgE No. (%) Positive Inhalant panel Food panel 0 696 (49.0) 182 (55.0) 1 130 (9.1) 42 (12.7) 2 148 (10.4) 26 (7.9) 3 145 (10.2) 29 (8.8) 4 76 (5.3) 13 (3.9) 5 47 (3.3) 4 (1.2) 6 37 (2.6) 11 (3.3) 7 22 (1.5) 4 (1.2) 8 28 (2.0) 2 (0.6) 9 20 (1.4) 3 (0.9) 10 9 (0.6) 0 (0.0) 11 10 (0.7) 3 (0.9) 12 8 (0.6) 0 (0.0) 13 8 (0.6) 0 (0.0) 14 5 (0.4) 4 (1.2) 15 1 (0.1) 1 (0.3) 16 5 (0.4) 2 (0.6) 17 2 (0.1) 0 (0.0) 18 3 (0.2) 0 (0.0) 19 3 (0.2) 1 (0.3) 20 1 (0.1) 0 (0.0) 21 4 (0.3) 1 (0.3) 22 2 (0.1) 1 (0.3) 23 2 (0.1) 0 (0.0) 24 1 (0.1) 0 (0.0) 25 0 (0.0) 0 (0.0) 26 1 (0.1) 0 (0.0) 27 2 (0.1) 0 (0.0) 28 0 (0.0) 1 (0.3) 29 1 (0.1) 0 (0.0) 30 1 (0.1) 0 (0.0) 31 0 (0.0) 0 (0.0) 32 0 (0.0) 0 (0.0) 33 1 (0.1) 0 (0.0) 34 1 (0.1) 0 (0.0) 35 1 (0.1) 1 (0.3) Total 1,421 (100) 331 (100) 원수를 Table 5에나타내었다. 35종의알레르겐에대한특이 IgE 가 1개라도 class 1 이상의결과를보인환자를양성으로판정하여양성률을계산하였으며, 평균양성항원수는 35종의알레르겐에대해서환자별양성항원수의평균을의미한다. 흡입형패널의양성률은 51.0% 였고평균양성항원수는 2.4±4.1 개였다. 음식형패널의양성률은 45.0% 였고평균양성항원수는 2.0±4.1개였다. 연령별양성률은흡입형패널의경우 11세에서 20세이하가 68.3% 로가장높았고음식형패널도 11세에서 20세이하가 63.3% 로가장높았다. 평균양성항원수는흡입형패널의경우 11세에서 20세이하가 3.4±4.7 개로가장높았고음식형항원의경우 21세에서 30세이하가 3.6±5.9 개로가장높았다. 4. 동시양성항원의조합동시양성항원의연관성분석을위해각항원양성환자수중다른항원도양성인환자수를백분율로표시하여 Table 6, 7에나타냈다. 흡입형패널에서동시양성으로잘나타나는항원의조합중동시양성률 90% 이상은 Mite-f+Mite-p+/Mite-p (96.0 %), Mite-f+housedust+/housedust (93.6%), Mite-p+housedust+/housedust (90.6%), Bermuda grass+acacia+/acacia (90.3%), white oak+japanese cedar+/japanese cedar (90.5%), Mite-f+cladosporium+/cladosporium (91.7%) 의 6종이었다. 음식형패널의경우 90% 이상은 milk+cheese+/cheese (93.8%) 외 61종이었으나동시양성항원을갖는환자수가 10 이하인것이많아이들항원간의연관성을결론내기에는충분하지않았다. 고빈도의양성률을가진항원 (Mite-f, Mite-p, house dust) 과다른항원들간의동시양성률이높게나타났고, 교차반응이있는것으로알려진수목 (tree), 목초 (grass), 잡초 (weed) 의꽃가루항원간에, 또꽃가루항원과과일, 채소, 콩류간에, 쌀, 보리, 밀등곡류간에, 우유와치즈간에, 곰팡이류간에, 집먼지진드기 2 종및집먼지간에, 바퀴, 새우, 게간에, 개와고양이간에동시양성률이높았다. Table 5. Positivity of allergen-specific IgE and an average number of simultaneously positive allergens according to age groups Inhalant panel Food panel Age (years) No. tested No. (%) positive Average No. of positive allergens (mean±sd) No. tested No. (%) positive Average No. of positive allergens (mean±sd) 10 394 212 (53.8) 2.1±3.3 127 47 (37.0) 1.3±2.4 11-20 246 168 (68.3) 3.4±4.7 30 19 (63.3) 1.6±1.7 21-30 174 102 (58.6) 3.0±4.7 36 22 (61.1) 3.6±5.9 31-40 219 110 (50.2) 2.7±5.2 56 27 (48.2) 2.8±5.2 41-50 180 69 (38.3) 1.7±3.3 36 16 (44.4) 2.2±6.2 51-60 115 40 (34.8) 1.6±3.8 29 11 (37.9) 1.4±3.0 >60 93 24 (25.8) 1.1±2.6 17 7 (41.2) 1.9±3.8 Total 1,421 725 (51.0) 2.4±4.1 331 149 (45.0) 2.0±4.1

452 김현수 김대중 이성규 Table 6. Allergens showing simultaneously positive results in the Korean inhalant panel of MAST-CLA Positive No. Allergens showing simultaneously positive results Food Crab 34 Mite-f (91.2%), Mite-p (79.4%), Shrimp (73.5%), Cockroach (70.6%) Egg white 25 Mite-f (72.0%), Mite-P (72.0%) Milk 36 Mite-f (83.3%), Mite-P (72.2%) Peach 37 White oak (75.7%), Mite-f (75.7%), Mite-p (70.3%) Shrimp 57 Mite-f (78.9%), Mite-p (70.2%) Soybean 29 Mite-f (79.3%), Tree Acacia 31 Bermuda grass (90.3%), White oak (83.9%), Short ragweed (77.4%), Orchard grass (74.2%), Timothy grass (71.0%), Rye (74.2%), Mite-f (71.0%) Ash mix 36 White oak (88.9%), Mite-f (80.6%), Mite-p (75.0%), House dust (72.2%) Birch/alder 54 White oak (81.5%), Mite-f (72.2%) Black Willow 28 Birch/alder (78.6%), Ash mix (75.0%) Cedar, Japan 21 White oak (90.5%), Mite-f (85.7%), Short ragweed (81.0%), Timothy grass (76.2%), Ash mix (71.4%), Mite-p (71.4%), Cocks foot (71.4%), Dandelion (71.4%) Hazelnut 47 Mite-f (78.7%), Birch/alder (74.5%), Mite-p (72.3%) Poplar mix 30 Mite-f (83.3%), House dust (80.0%), Mite-p (76.7%), Short ragweed (76.7%), Bermuda grass (73.3%), Ash mix (70.0%), White oak (70.0%) Sycamore mix 24 White oak (87.5%), Mite-f (83.3%), Short ragweed (83.3%), Bermuda grass (83.3%), Dandelion (83.3%), Goldenrod (75.0%), Orchard grass (75.0%), Timothy grass (75.0%), Mite-p (75.0%), Rye (75.0%), Ash mix (70.8%), Poplar mix (70.8%), House dust (70.8%) White oak 128 Grass Bermuda grass 73 Rye (74.0%), Short ragweed (71.2%) Orchard grass 65 Timothy grass (80.0%), Rye (80.0%), Bermuda grass (75.4%), White oak (72.3%), Short ragweed (70.8%) Rye 75 Timothy grass (76.0%), Russian thistle (72.0%), Bermuda grass (72.0%) Timothy grass 69 Rye (82.6%), Orchard grass (75.4%), White oak (72.5%), Bermuda grass (72.5%), Short ragweed (71.0%) Weed Dandelion 50 Short ragweed (84.0%), Mite-f (82.0%), Mite-p (74.0%) Goldenrod 48 White oak (81.3%), Mite-f (79.2%), Mite-p (75.0%) Mugwort 70 Mite-f (82.9%), Mite-p (71.4%) Pigweed mix 28 Short ragweed (89.3%), Bermuda grass (82.1%), White oak (75.0%), Russian thistle (75.0%), dandelion (75.0%), Mugwort (75.0%), Mite-f (75.0%), Orchard grass (71.4%), Timothy grass (71.4%), Rye (71.4%), Goldenrod (71.4%), House dust (71.4%) Russian thistle 66 Rye (81.8%), Short ragweed (77.3%), Bermuda grass (74.2%), Timothy grass (72.7%), White oak (71.2%) Short ragweed 107 Mold Alternaria 66 Mite-f (77.3%), Short ragweed (72.7%), Aspergillus (72.7%), House dust (72.7%), Mite-p (72.7%) Aspergillus 164 Mite-f (83.5%), Mite-p (79.3%) Cladosporium 36 Mite-f (91.7%), Mite-p (88.9%), Aspergillus (88.9%), Alternaria (80.6%), Penicillium (72.2%), House dust (72.2%) Penicillium 53 Mite-f (81.1%), House dust (79.2%), Aspergillus (77.4%), Mite-p (75.5%), Alternaria (69.8%) Epithelium Cat 117 Mite-f (86.3%), Mite-p (82.1%), Dog (80.3%) Dog 165 Mite-f (87.9%), Mite-p (85.5%), House dust (71.5%) Insect Cockroach 139 Mite-f (89.9%), Mite-p (80.6%), House dust (70.5%) Dust House dust 298 Mite-f (93.6%), Mite-p (90.6%) Mite Mite-farinae 573 Mite-p (82.9%) Mite-pterony 495 Mite-f (96.0%) 고찰본연구에서도국내다른보고 [1-5] 와마찬가지로 mite-farinae 와 mite-pterony에대한양성률이가장높았다. 이두항원이외의고빈도항원의순서나각항원의양성률은보고자마다약간의차이가있는데이의원인으로다음과같은이유를생각해볼수있겠다. 첫째는 MAST 검사가의뢰되는대상군이전체인구가아니라외래로찾아오는환자중여러과의임상의의선택에의해서대상군이결정되므로각검사실의양성률이달라질수있다. 두번째는쓰고있는 MAST panel의 lot 마다차이가있을수있 다. 다른검사에비해알레르겐특이 IgE 검사는사용되는알레르겐항원의특성, 제조방법에따라일치율이낮고아직까지참고방법이라고할만한것이개발되어있지않다. 또한동일회사제품이라도다른면역검사에비해 lot 간의결과차이가큰데이또한알레르기물질의원료차이, 추출법차이, 부착법차이로발생한다. 세번째이유로양성판정기준이과거논문에서는 2+ 이상을양성기준으로잡았으나현재는 1+ 이상을양성으로판정하므로과거논문에비해양성률이높게나타날수있다 [8]. MAST CLA가처음개발되었을때는알레르기증상이없는정상인에서도 1+ 가흔히나타나므로양성판정기준을 2+ 이상으로정했었

MAST CLA 알레르기검사에서동시양성알레르겐의분석 453 Table 7. Allergens showing simultaneously positive results in Korean Food panel of MAST CLA Positive No. Allergens showing simultaneously positive results Food Baker's yeast 3 Peanut (100%), Birch/alder (100%), White oak (100%), Mugwort (100%), Cat (100%), Dog (100%), Cockroach (100%), House dust (100%), Mite-f (100%), Mite-p (100%), Alternaria (100%), Aspergillus (100%) Barley 9 Wheat (100%), Peanut (100%), Mite-f (88.9%), Rice (88.9%), Mite-p (77.8%), Soybean (77.8%), Citrus mix (77.8%), Garlic (77.8%), Onion mix (77.8%), Cockroach (77.8%), House dust (77.8%) Beef 3 Milk (100%) Cheese 16 Milk (93.8%) Chicken 5 Soybean (80.0%), Egg white (80.0%), Peanut (80.0%), House dust (80.0%), Codfish (80.0%), Wheat (80.0%) Citrus mix 10 Wheat (90.0%), Peanut (90.0%), Peach (80.0%), Cockroach (80.0%), Mite-f (80.0%), Soybean (70.0%), Rice (70.0%), Barley (70.0%), Onion mix (70.0%), White oak (70.0%), Rye (70.0%), Mugwort (70.0%), Short ragweed (70.0%) Codfish 7 Shrimp (71.4%), Mite-f (71.4%) Crab 8 Shrimp (75.0%), Cockroach (75.0%), Mite-f (75.0%) Egg white 24 Garlic 9 Peanut (88.9%), Wheat (77.8%), Barley (77.8%), Mite-f (77.8%) Milk 22 Cheese (68.2%) Onion mix 10 Mite-f (100%), Wheat (90.0%), Cockroach (90.0%), Peanut (90.0%), White oak (90.0%), Short ragweed (90.0%), Rye (90.0%), Soybean (80.0%), Rice (80.0%), Citrus mix (70.0%), Barley (70.0%), Mugwort (70.0%), House dust (70.0%), Mite-p (70.0%) Peach 14 Peanut 19 Mite-f (68.4%), Soybean (63.2%), Wheat (63.2%), Pork 2 Soybean (100%), Milk (100%), Cheese (100%), Egg white (100%), Chicken (100%), Codfish (100%), Beef (100%), Wheat (100%), Peanut (100%), House dust (100%) Rice 11 Wheat (90.9%), Peanut (90.9%), Mite-f (90.9%), Soybean (81.8%), Barley (72.7%), Onion mix (72.7%), White oak (72.7%), Rye (72.7%), Short ragweed (72.7%), Cockroach (72.7%), House dust (72.7%), Mite-p (72.7%) Salmon 2 Soybean (100%), Milk (100%), Cheese (100%), Egg white (100%), Crab (100%), Shrimp (100%), Tuna (100%), Chicken (100%), Codfish (100%), Wheat (100%), Rice (100%), Barley (100%), Garlic (100%), Peanut (100%), House dust (100%) Shrimp 16 Soybean 16 Peanut (75.0%), Wheat (68.8%) Tuna 5 Shrimp (80.0%) Wheat 16 Peanut (75.0%), Mite-f (68.8%), Soybean (68.8%), Rice (62.5%) Tree Birch/alder 13 White oak (100%), Mite-f (92.3%), Mite-p (92.3%) White oak 28 Mite-f (82.1%), Mite-p (71.4%) Grass Rye 25 Short ragweed (76.0%) Weed Mugwort 24 Mite-f (75.0%) Short ragweed 23 Rye (82.6%), Mite-f (73.9%) Mold Alternaria 10 Mite-f (90.0%), Mite-p (80.0%), Mugwort (80.0%), House dust (80.0%), Cat (80.0%), Dog (70.0%), Cockroach (70.0%), Short ragweed (70.0%), Aspergillus (70.0%) Aspergillus 19 Mite-f (89.5%), Mite-p (89.5%) Cladosporium 8 Mite-f (100%), Mite-p (87.5%), Cat (87.5%), Mugwort (75.0%), Short ragweed (75.0%), Alternaria (75.0%), Aspergillus (75.0%), House dust (75.0%) Epithelium Cat 18 Mite-p (94.4%), Mite-f (88.9%), Dog (83.3%) Dog 22 Mite-f (90.9%), Mite-p (86.4%), Cat (68.2%) Insect Cockroach 25 Mite-f (80.0%), Mite-p (72.0%) DustHousedust 36 Mite-f (94.4%), Mite-p (94.4%) Mite Mite-farinae 99 Mite-p (68.7%) Mite-pterony 72 Mite-f (94.4%) 으나, 현재는알레르기증상이없는환자에서나타나는 specific IgE도의미가있는것으로보고있다. 네번째는지역에따라원인항원의종류와양성률이약간씩다른점을들수있다. 피부단자시험검사의양성률도대상환자, 검사방법과사용되는알레르겐, 양성판단기준, 지역에따라다양한결과를보이는데 MAST 검사보다는민감도가높은것으로알려져있다. 알레르겐양성률은 10대가가장높았고고령으로갈수록양성 률과양성항원수가적어지는양상을보였는데, 이는연령별총 IgE가 10-15 세사이에서가장높은현상과관련이있는것으로생각되었다 [9]. 본논문에서 MAST 음식형패널과흡입형패널내에서의동시양성항원의양상을분석하였는데분석하는방법이 두항원동시양성환자수 / 두항원중한항원양성환자수 를백분율로표시하였으므로, 두항원중양성률이낮은항원을분모로했을

454 김현수 김대중 이성규 때양성률이높은항원 (Mite-f, Mite-p, house dust) 과의동시양성률이높게나타났으며, 또한교차반응이있는것으로알려진알레르겐사이에동시양성률이높았다 [6, 7, 10, 11]. 교차반응이있는것으로알려진알레르겐은수목 (tree), 목초 (grass), 잡초 (weed) 의꽃가루 (pollen) 항원간에, 또꽃가루음식증후군 (pollen-food syndrome) 을일으킨다는꽃가루항원과과일, 채소, 콩류간에, 쌀, 보리, 밀등곡류간에, 곰팡이류간에, 우유와치즈간에, 집먼지진드기 2종및집먼지간에, 바퀴, 새우, 게등절지동물및갑각류간에, 개와고양이사이에동시양성률이높았다. 이들교차반응의원인으로알려진분자 (molecule) 단위의알레르겐은꽃가루항원과과일, 채소, 콩류간에는 Fagales 1군 (Bet v 1 from birch; Aln g 1 from alder; Cor a 1 from hazelnut; Qua 1 from white oak; Gly m 4 from soybean; Ara h 8 from peanut 등 ) 과 Profilin군 (Bet v 2 from birch; Cor a 2 from hazelnut; Fra e 2 from ash; Pla a from sycamore; Cyn d 12 from Bermuda grass; Lol p 12 from rye; Ory s 12 from rice; Phl p 12 from timothy grass; Amb a from short ragweed; Art v 4 from mugwort; Gly m 3 from soybean; Pru p 4 from peach; Ara h 5 from peanut; Cor a 2 from hazelnut 등 ), Polcalcins군 (Aln g 4 from alder; Bet v 3, Bet v 4 from birch; Fra e 3 from ash; Cyn d 7 from Bermuda grass; Phl p 7 from timothy grass; Amb a from short ragweed; Art v from mugwort 등 ), Oleaceae 1군 (Fra e 1 from ash; Lol p 11 from rye; Phl p 11 from timothy grass; Sal k from Russian thistle 등 ), Grasses 1군 (Cyn d 1 from Bermuda grass; Hor v 1 from barley; Lop p 1 from rye, Ory s 1 from rice; Phl p 1 from timothy grass; Sec c 1 from rye; Tri a 1 from wheat 등 ), Grasses 5군 (Cyn d 5 from Bermuda grass; Hor v 5 from barley; Lop P 5 from rye, Phl p 5 from timothy grass; Sec c 5 from rye 등 ), Ragweed 1군 (Cry j 1 from Japanese cedar; Amb a 1 from short ragweed; Art v from mugwort 등 ), Compositae 1군 (Art v 1 from mugwort 등 ), non-specific lipid transfer protein (Art v 3 from mugwort; Hor v from barley; Pru p 3 from peach; Tri a from wheat; Ara h from peanut; Cor a 8 from hazelnut 등 ) 을생각할수있겠다 [10, 11]. Peanut과 soy 등콩과류의식물은식물알부민 (Ara h 2, h 6, h 7 from peanut 등 ) 과 7S 글로불린 (Ara h 1 from peanut; Cor a 11 from hazelnut; Gly m 1 from soybean), 11S globulin (Ara h 3, h 4 from peanut 등 ) 간의교차반응으로생각된다. 쌀, 보리, 밀등곡류간의동시양성은흔하게발견되나원인이되는항원에대해서는아직불확실하다. 치즈와우유는 80% 가같은 casein 성분 (Bos d 8) 이므로동시양성이대부분이었다. 곰팡이류간의교차반응을일으키는알레르겐으로는 mold의 enolase (Alt a 11 from alternaria; Asp f 22 from aspergillus; Cla h 6 from cladosporium; Pen c 22 from penicillium 등 ) 을생각해볼수있다. 집먼지진드기 2종및집먼 지는대부분의경우동시양성을보였는데이는진드기항원 1군 (Der f 1 from Dermatophagoides farinae; Der p 1 from Dermatophagoides pteronyssinus 등 ) 과진드기항원 2군 (Der f 2 from Dermatophagoides farinae; Der p 2 from Dermatophagoides pteronyssinus 등 ) 사이의교차반응때문인것으로해석된다. Housedust mite, cockroach, crab, shrimp 간의동시양성은무척추동물에있는 tropomyosin군 (Der f 10 from Dermatophagoides farinae; Der p 10 from Dermatophagoides pteronyssinus; Per a 7 from cockroach; Cla f 1 form crab; Pen? from shrimp 등 ) 간의교차반응으로생각된다. Pork, beef, chicken, cat, dog 등의포유류들끼리동시양성을잘보인다. 이는혈청 albumin의교차반응때문으로해석되는데본연구에서도개와고양이사이의동시양성률이높았다. Egg와 chicken의교차반응 (Bird-egg syndrome) 의주원인은 Gal d 5 (albumin: a-livetin) 이며생선류는 parvalbumins군 (Cad c 1 from codfish; Sal s 1 from salmon 등 ) 이주요한교차반응항원인데 [10, 11] 본연구에서는양성환자수가적어확실하지않았으나 salmon 양성환자 2명이모두 codfish에양성을보였고, chicken 양성환자가 5명중 4명 (80%) 이 egg white 양성이었다. 교차반응또는동시양성항원에관한국내보고로는특정항원간의교차반응을실험으로증명한논문들 [7, 12, 13] 과, 항원들을수목류, 목초류, 잡초류꽃가루군, 동물군, 집먼지진드기군등의군 (group) 으로나누어이들군간의동시양성률을구한보고가있었으나 [6] 본연구에서와같이 MAST CLA 검사의모든항원에대하여개별항원간의동시양성률을구한것은저자들이찾아본바로는국내외최초의시도이며본연구의결과는 MAST CLA를이용하는검사실에서결과해석시유용한자료로사용될수있을것이다. 본연구에서동시양성결과가각각의알레르겐에노출되어생긴동시감작 (co-sensitization) 인지, 한알레르겐에만노출되었으나비슷한구조를가진알레르겐사이의교차반응 (cross-reactivity) 에의해노출된적이없는알레르겐에대해서도양성으로나타났는지는현재항원추출법을사용하는검사방법으로는불가능하다. 알레르기검사의다중양성결과를해석하는데있어각검사실에서사용하고있는알레르겐물질의특성에대한정확한정보가필요한데아직까지알레르기를일으키는물질에서추출한항원을이용하는검사법으로는규명된알레르겐도있으나규명되었더라도분자량만알수있는규명되지않은물질이많이포함되어있다. MAST Korean panel도 Acacia, BirchAlder mix, Citrus mix, Dandelion, Garlic, Goldenrod, Onion mix, Orchard grass 는제조회사에서도추출물의내용을규명하지않았으므로알레르겐분자단위의교차반응유무를알기에는어려움이있었다. 최근에는각각의알레르기반응을일으키는분자 (molecule) 단위의알레르겐항원의규명과아미노산배열, 3차원구조, 유전자구조가밝혀지고있으며 [10, 11] 이들알레르겐분자에따른교차반응이규명되고있다. 또한 birch 알레르겐인 Bet v 1 등과같은

MAST CLA 알레르기검사에서동시양성알레르겐의분석 455 일부알레르겐분자에대해서는재조합항원 (rbet v 1) 을만들어환자혈청과반응하는것을확인하였으므로앞으로수년내에재조합항원으로만들어진알레르기진단시약이개발되면교차반응과동시감작의감별이가능하여알레르기질환의진단및면역치료에유용하게이용될것으로기대된다. 요약배경 : 알레르기검사시여러알레르겐에대해동시양성인환자가흔히발견된다. 본연구에서는 MAST CLA 검사결과를분석하여 MAST CLA 한국형패널 ( 흡입형과음식형의 2종류 ) 내에서동시양성항원의양상을분석하고자하였다. 방법 : 2004년 3월부터 2005년 3월까지 13개월동안분당제생병원진단검사의학과에의뢰되었던 MAST 검사결과를분석하였다. 이기간동안흡입형알레르기검사가총 1,421건, 음식형알레르기검사가 331건이의뢰되었다. 결과 : 흡입형패널에서각항원의양성률은 Mite-farinae (40.3 %) 와 Mite-pterony (34.8%) 가가장높았고음식형패널에서도두항원의양성률이가장높았다. 2개이상의항원에동시양성을보이는경우는흡입형패널이 41.9% (595/1421) 였고음식형이 32.3% (107/331) 이었다. 동시양성인항원의조합을분석하였는데고빈도의양성률을가진항원 (Mite-f, Mite-p, house dust) 과다른항원들간의동시양성률이높게나타났고, 교차반응이있는것으로알려진수목 (tree), 목초 (grass), 잡초 (weed) 의꽃가루항원간에, 또꽃가루음식증후군 (pollen-food syndrome) 으로일으킨다는꽃가루항원, 과일, 채소, 콩류간에, 쌀, 보리, 밀등곡류간에, 우유와치즈간에, 곰팡이류간에, 집먼지진드기 2종및집먼지간에, 바퀴, 새우, 게간에, 개와고양이간에동시양성률이높았다. 결론 : MAST CLA 검사의동시양성결과가여러항원들사이에발견되었는데특히교차반응이있는것으로알려진항원간에동시양성률이높았다. 이들동시양성결과가동시감작 (cosensitization) 인지교차반응 (cross-reactivity) 인지는알수없으나, 향후재조합항원을이용한알레르기진단시약이개발되면이현상을구분할수있을것으로기대된다. 참고문헌 1. Lee EJ, Piao YJ, Kim KH, Suhr KB, Lee JH, Park JK. The relationship among the clinical evaluation, total IgE, and allergen-specific IgE of MAST-CLA in atopic dermatitis. Korean J Dermatol 2003; 41: 197-206. ( 이은주, 표영준, 김경호, 서기범, 이증훈, 박장규. 아토피피부염환자의 MAST 화학발광법에의한알레르겐검사성적과임상평가와의상관관계. 대한피부과학회지 2003; 41: 197-206.) 2. Lim HS, Yoon JK, Lee HH. Allergen patterns using MAST CLA test in Korean pediatric patients. Korean J Clin Pathol 2001; 21: 292-7. ( 임환섭, 윤재균, 이현희. MAST CLA 시험을이용한한국소아에서의알레르겐양상. 대한임상병리학회지 2001; 21: 292-7.) 3. Park KI, Chun HS, Shin JW, Kim HS, Song KS. Allergen frequencies on MAST CLA by age groups using new Korean panel. J Clin Pathol Quality Control 1999; 21: 243-9. ( 박광일, 전혜선, 신원, 김현숙, 송경순. 새로운한국형알레르겐 panel을이용한 MAST CLA 알레르겐의연령별빈도. 임상병리와정도관리 1999; 21: 243-9.) 4. Yang SE, Oh HB, Hong SJ, Moon DH, Chi HS. Analysis of MAST chemiluminescent assay (MAST CLA) results performed in Asan medical center. Korean J Clin Pathol 1998; 18: 606-6. ( 양성은, 오흥범, 홍수종, 문대혁, 지현숙. 서울중앙병원에서시행된 MAST Chemiluminescent assay (MAST CLA) 검사결과의분석 : MAST CLA 검사의개선점파악을위한연구. 대한임상병리학회지 1998; 18: 660-6.) 5. Lee SR, Lee HR, Keum DG. Evaluation of the MAST-CLA allergy system (Korea IgE panel) for diagnosis of atopic allergy. Korean J Clin Pathol 1995; 15: 469-77. ( 이소라, 이혜림, 금동극. 아토피성알레르기진단에있어서 MAST-CLA 알레르기검사 ( 한국형 ) 에대한평가. 대한임상병리학회지 1995; 15: 469-77.) 6. Yu YI, Cho JS, Lee KH, Kim GH, Hong SM, Kim SW. A clinical statistics on allergens of allergic rhinitis: Prevalence of mixed sensitization. Korean J Otolaryngol 2003; 46: 48-53. ( 유영인, 조중생, 이건희, 김광훈, 홍석민, 김승우. 알레르기비염의기인항원에대한고찰 : 중복감작의분포. 대한이비인후과학회지 2003; 46: 48-53.) 7. Yun YY, Ko SH, Park JW, Hong CS. Cross-reactivity between pollens in patients sensitized to multiple pollens. Korean J Asthma Allergy Clin Immunol 1999; 19: 584-93. ( 윤영연, 고시환, 박중원, 홍천수. 다종꽃가루에대한피부반응양성환자들에서꽃가루간의교차반응에관한연구. 천식및알레르기 1999; 19: 584-93.) 8. 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 and Asthma Proc 2003; 24: 253-8. 9. Matsson P, Hamilton RG, Adkinson NF, Esch R, Homburger HA, Maxim P, et al. Evaluation methods and analytical performance characteristics of immunologic assays for human immunoglobulin E (IgE) antibodies of defined allergen specificities. National Committee for Clinical Laboratory Standards (NCCLS), Wayne, PA, Approved guideline I/LA20-A. 1997. 10. Mothes N, Horak F, Valenta R. Transition from a botanical to a molecular classification in tree pollen allergy: Implications for diagnosis and therapy. Int Arch Allergy Immunol 2004; 135: 357-73. 11. Ferreira F, Hawranek T, Gruber P, Wopfner N, Mari A. Allergic crossreactivity: from gene to clinic. Allergy 2004; 59: 243-67.

456 김현수 김대중 이성규 12. Lee KY, Jeong BJ, Lee SY, Kim KE, Kim DS. An immunologic study of cross-reaction among German cockroach, shrimp and crab antigens in Korea. Korean J Allergy 1992; 12: 33-45. ( 이기영, 정병주, 이수영, 김규언, 김동수. 한국에서식하고있는독일바퀴, 새우, 게항원의교차반응에관한면역학적연구. 알레르기 1992; 12: 35-45.) 13. Lee KY, Lee SY, Jeong BJ, Kim KE, Kim DS. Cross-reactivity among four cereals: rice, barley, wheat flour and buckwheat flour. Korean J Allergy 1993; 13: 65-74. ( 이기영, 이수영, 정병주, 김규언, 김동수. 쌀항원의면역학적특성과보리, 밀가루및메밀항원과의교차반응에관한면역학적연구. 알레르기 1994; 4: 65-74.)