Component resolved diagnosis in food allergy

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Component Resolved Diagnosis in Food allergy

Presented by Sadudee Boonmee, MD.

December20, 2012

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  • - There is currently no known structure that is commom for all allergen component or epitope - Every species contain species specific allergen epitope and antibody form to these structure bind only to allergen epitope in this particular species - Protein with similar structure are often present in biologically related species  Ab formed against such protein structure on a protein from several different species thereby causing cross-reactivity
  • Primary species – specific allergen
  • Bird-egg syndrome Primary sensitization is to airborne bird allergen with secondary sensitization or cross-reactivity with albumin in egg yolk(Gal d 5)Pt. respiratory symptom eg. Rhinitis a/o asthma with bird exposured and immediated allergic symptom with egg ingestion
  • Heated egg white: heating liquid egg white at 90 C for 60 min  freeze dry ทำเป็น powder by homogenization Raw egg white : directed freeze dry liquid egg before homogenized  dose not change allergenicity
  • A = positive raw and heatB = positive rawC= negative raw & heated
  • ROC curveThe clinical decision points are cutoff levels at which foodprovocations might be excluded because of the high probability ofhaving a true food allergy (positive decision point) or, on the otherend of the scale, the high probability of being tolerant (negativedecision point).
  • The reason is that ovomucoid mostly retains its allergenicity afterextensive heating. It comprises 3 protein domains, each stabilizedby 3 intradomain disulfide bonds.15
  • Casein : heat stable Whey : heat slightly reduction in allergenicityBSA = bovine serum albumin  minor allergen also report allergic reaction
  • Clinical of beef allergy : lip edema, urticaria, cough, rhinitis
  • αs1-caseins sensitization = 100% κ-caseins sensitization = 91.7%
  • AAR severity was classified based on symptoms as mild, moderate, andsevere, according to investigator-defined criteria. Mild reactions = with cutaneous symptoms (angioedema excluded), rhinitis, or conjunctivitis.Moderate reactions = angioedema or gastrointestinal symptoms, whichmight or might not be associated with those considered mild. Severe reactions = involving the lower respiratory tract (loss of voice, dyspnea,wheezing, stridor, and/or cyanosis) or systemic symptoms (loss of consciousness,weakness, or dizziness).
  • Six children experienced 8 AARs. It is worth noting that children 4 and 5 had 2 potentially severeSpecific IgE levels against milk and casein were greater than 24KUA/L in 5 cases. Five of the 6 children had asthma.
  • At least 2 consecutive food challenge testFirst proven by DBPCFC and follw up over time
  • Alphalactalbumin,betalactoglobulinและ kappa casein sIgE detect ค่ากว่า 0.3 ISU/L Table 3 บอกว่า ถ้าundetectAlphalactalbumin,betalactoglobulinและ kappa casein ตั้งแต่แรก มี likelyhoodที่จะ7.2, 2.7 และ 3.8 เท่า Difference time in tolerant Alphalactalbumin if < o.3 ISU/Lครึ่งนึง หายตอน 18 เดือน แต่ถ้า > 0.3 ISU/L ครึ่งนึงจะ tolerant ได้ตอน 60 เดือน
  • Targeted dx testing with Gly m 4 is strongly recommend in pollen – sensitized pt. with suspicious of soy asllergyEsp. if soyextrac test are negative.Some Gly m 4 sensitized pt. can show low or even negative IgE result with soy extract due to low Gly m4 content in extract
  • 86% of soy anaphylaxis have Gly m5/Gly m6 IgE positive 55% of moderately soy allergic have Gly m5/Gly m6 IgE positive 33% of mild soy allergic have Gly m5/Gly m6 IgE positive
  • The patients were recruited in 3 European allergy centers—Zurich(Switzerland), Odense (Denmark), and Milan (Italy)—according to protocolsapproved by the Ethical Committees of the respective centers. The primaryinclusion criterion was a positive food challenge (DBPCFC) with soy or aconvincing history of anaphylactic reactions to soy.: IgE-reactive proteins were identified from a soybean cDNA expression library(natural soybean source, or expressed in Escherichia coli.)
  • TriaA_TI = alpha-amylase/tyrpsin inhibitorPositive result to wheat flour extract อาจไม่ correlate กับ clinical symptom ซึ่งพบว่า Wheat commonly cross reacts with grass pollen ทำให้มีการ over Dx of wheat allergy เช่น บางกรณีที่แพทย์ตรวจ SPT to wheat or sIgE to wheat แล้ว +veในคนไข้ grass allergy เกิด cross reactive แพทย์อาจแปลผลว่าเป็น Wheat allergy and avoid wheat in diet การพัฒนา in vitro Dxที่เป็น species specific for wheat น่จะช่วย improve การวินิจฉัย wheat allergy
  • HelsinkiUniversity Hospital for Skin and Allergic Diseases (n = 29) or to theTampere University Hospital (n = 11)
  • Studyat UK
  • - Anaphylactic reaction after contact with peanut 1 peanut SPT 8 mmand/or peanut specific IgE 15 kUA/L
  • Constellation = กลุ่ม
  • Pan-allegen familyLTP: (PR-14)- distributed in fruits,vegetables and pollens.Their high resistance to heat treatment and proteolytic digestion and their association with systemic and severe symptoms have led to the proposal ofLTP as a model Of true plant food allergen.Profilin- minor allergen, cross-reactions betw plants and foods- actin-binding proteins in that are responsible for regulating the normal distribution of filamentous acting networksPR pathogenesis-related protien- innate defense barriers to physical stress or infection by fungus, virus or bacteria
  • Component resolved diagnosis in food allergy

    1. 1. Sadudee Boonmee, MDDivision of Allergy and ImmunologyDepartment of PediatricsKing Chulalongkorn Memorial Hospital
    2. 2. Topic outline• Introduction• Important protein families• Allergen from animal origin (Egg, CM)• Allergen from plant origin (Soy, wheat and peanut)
    3. 3. Currently available tests detect only sensitization,not clinical allergy, cannot predict prognosis and severityNatureAllergenicsource contain a mixture of allergenic and non-allergenic molecules
    4. 4. Introduction• Specific IgE determined using allergen extracts as test allergens have to 2 type of problem 1. the difficulty of starndardizing the allergens used as substrates ( differ in allergenicity variability of allergen source) 2. can not differentiated between primary sensitization and immunological cross-reactivity Borres et.al,Pediatric Allergy and Immunol 2011;22:454-461.
    5. 5. Introduction• Both skin prick testing and specific IgE blood testing employ heterogeneous protein preparations  not always the best indicators of clinical reactivity• Component testing  designed to pinpoint the allergen source when cross-reactive allergen components are present. Borres et.al,Pediatric Allergy and Immunol 2011;22:454-461.
    6. 6. Introduction• Identifying whether the sensitization is genuine in primary (species-specific) or if it is due to cross-reactivity to similar protein structure may help to evaluate the risk of reaction on exposure to difference allergen source Clinical and Experimental Allergy;2010 ,40: 896-904
    7. 7. Basic of allergen component1. Almost anything containing proteins can be an allergen source - each allergen source contains many different allergenic protein (allergen component) - each allergen component commonly has several different epitopes - epitope is the actual three-dimensional binding site for an antibody Clinical and Experimental Allergy;2010 ,40: 896-904
    8. 8. Basic of allergen component2. Protein stability - allergen that stable to heat and digestion are more likely to cause severe reaction - allergen that heat and digestion labile are more likely to be tolerateed or only cause mild/local symptom Clinical and Experimental Allergy;2010 ,40: 896-904
    9. 9. Basic of allergen component3. Allergen component name - the first 3 letter of the genus, follow by the first letter of the species and the number indicating the order of allergen identification - Latin designation of peanut is Arachis hypogaea thus Ara h 1 designated allergen number 1 from peanut Clinical and Experimental Allergy;2010 ,40: 896-904
    10. 10. Basic of allergen component• Production technique of allergen component can be - biotechnological in “recombinant” from - “purified” from (original source)
    11. 11. Important allergen families• Most allergen component belong to a limited number of protein families• IgE antibodies in the same protein family often cross-reactive, and classifying allergen component into protein families can answering question on cross-reactivity
    12. 12. Important allergen familiesPlant allergenLTP (non-specific Lipid Transfer Protein, nsLTP) - A protein stable to heat and digestion causing reactions also to cooked foods. - Often associated with systemic and more severe reactions in addition to OAS. - Often associated with allergic reactions to fruit and vegetables in southern Europe.Storage proteins - Proteins found in seeds serving as source material during the growth of a new plant. - Often stable and heat-resistant proteins causing reactions also to cooked foods.
    13. 13. Important allergen familiesPR-10 protein,Bet V1 homologue - A heat labile protein, cooked foods are often tolerated. - Often associated with local symptoms such as oral allergy syndrome (OAS). - Often associated with allergic reactions to fruit and vegetables in northern Europe.Profilin -An actin-binding protein showing great homology and cross-reactivity even between distant related species. - Recognized as a minor allergen in plants and plant related foods. - Seldom associated with clinical symptoms but may cause demonstrable or even severe reactions in a small minority of patients.CCD - Cross-reactive carbohydrate determinants are seldom associated with clinical symptoms but may cause demonstrable or even severe reactions in a small minority of patients.
    14. 14. Important allergen familiesAnimal allergenLipocalin - Stable proteins and important allergens in animals - Allergen components displaying limited cross-reactivity between species.Parvalbumin - A major allergen in fish. - A marker for cross-reactivity among different species of fish and amphibians. - A protein stable to heat and digestion causing reactions also tocooked foods.
    15. 15. Important allergen familiesTropomyosin - An actin-binding protein in muscle fibres. - A marker for cross-reactivity between crustaceans, mites and cockroach.Serum albumin - A common protein present in different biological fluids and solids e.g. cow’s milk and beef, eggs and chicken. - Cross-reactions between albumins from different animal species are well known, for example between cat and dog and cat and pork.
    16. 16. Allergen of animal origin
    17. 17. Egg (Gallus domesticus)Allergen component in egg white Gal d 1, 2, 3, 4 Gal d 5 alpha-livetin (serum chicken albumin) Clinical& experimental allergy; 2010: 40: 1442-1460
    18. 18. Egg (Gallus domesticus) Gal d 1(ovumucoid) - 10% of total egg white protein - stability against to heat and digestion by protease (strong disulfide bonds)  capacity to stimulate a specific immune response - sIgE Ab to Gal d 1  helpful in prognosis and diagnosis of egg allergy - High concentration of ovomucoid-sIgE associated with persistent egg allergy (raw or cooked egg ) - Low concentration of ovomucoid-sIgE associated with tolerance to heated egg Clinical& experimental allergy; 2010: 40: 1442-1460
    19. 19. Egg (Gallus domesticus) Gal d 2 (ovalbumin) - heat-labile, IgE - binging epitopes on OVA might be detroyed after heating  less allergenic - children who have sIgE primary to OVA likely to tolerate heated egg Clinical& experimental allergy; 2010: 40: 1442-1460
    20. 20. Egg (Gallus domesticus) Gal d 3(ovotransferrin) - nonheme iron-binding - heat-labile allergen - sIgE Ab to ovotransferrin in Dx of egg allergy not been determined Gal d 4 (lysozyme) - lysozyme commomly used as a food preservative(antibacterial) - egg allergic pt. who sensitized to lysozyme may react when exposured to such product Clinical& experimental allergy; 2010: 40: 1442-1460
    21. 21. Egg (Gallus domesticus)Allergenic component in egg yolk : Gal d 5 Gal d 5 (alpha-livetin) = chicken serum albumin - bird-egg syndrome Vitellenin(apovitellenin I) Role in egg allergy apoprotein B (apovitellenin VI) remain unclear Clinical& experimental allergy; 2010: 40: 1442-1460
    22. 22. • Objective: to evaluate the clinical usefulness and added diagnostic value of measurements of IgE antibodies to egg white, ovalbumin, and ovomucoid in children with egg allergy.• Methods: 108 children age 14 mo – 13 y (median age, 34.5 mo) with suspected egg allergy underwent double-blind, placebo controlled food challenges with raw and heated egg.• The outcomes of the challenges were related to the serum concentration of specific IgE antibodies and total IgE by using ImmunoCAP JACI 2008;122:583-588
    23. 23. • Pt. devided into 3 group ( immediated reactions to OFC) - Group A (n=38) : positive challenge for heated egg white - Group B (n=29) : tolerated heated egg white, positive challenge to raw egg white - Group C (n=41) : tolerated both heated and raw egg white• Serum of all pt. obtain before food challenge - sIgE egg white, sIgE to ovalbumin, sIgE to ovomucoid, total IgE  ImmunoCAP JACI 2008;122:583-588
    24. 24. Results Heated EW + Raw EW + Heated & raw EW - Heated EW + Raw EW + Heated & raw EW - JACI 2008;122:583-588
    25. 25. Heated Raw Heated Raw Heated & raw EW -EW + EW + Heated & raw EW - EW + EW +Heated Raw Heated RawEW + Heated & raw EW - EW + EW + Heated & raw EW - EW + JACI 2008;122:583-588
    26. 26. children allergic to raw egg white(ie, groups A and B vs group C; A)sIgE Ab to egg white well in diagnosis of reactions to raw eggwhite- positive decision point was 7.4 kUA/L- negative decision point was 0.6 kUA/Lchildren allergic to heated egg white(ie, group A vs groups B and C; B).sIgE Ab to ovomucoid showed the best results inpatients who react to heated egg white- positive decision point was 10.8 kUA/L- negative decision point was 1.2 kUA/L
    27. 27. • Quantification of sIgE to OVM could be useful in guiding physician in decision whether to perform a challenge or not• OVM > 11 kUA/L  high risk of reaction to heated and raw egg• OVM < 1 kUA/L  low risk of reaction to heated egg (pt. may react to raw egg)Clinical implications: Measurement of specific IgEantibodies to egg white and ovomucoid might behelpful in guiding evaluations of children for allergy toraw egg or heated egg (eg, in cakes/cookies). JACI 2008;122:583-588
    28. 28. Cow’s milk (Bos domesticus)Caseins Major allergen in milkWheyCaseins= 80% of total proteinβ lactoglobulin (β-LG) not present in human milk Curr Opin Allergy Clin Immunol 11: 216-221
    29. 29. Cow’s milk (Bos domesticus) α-lactoglobulin (Bos d 4) - Functional subunit of whey lactose syntase - controversial role in milk sensitization - 80% of CMPA react to Bos d 4 β-lactoglobulin (Bos d 5) - most abundant whey protein - Pt. have allergic reaction to β-lactoglobulin 13-76% Bovine serum albumin (BSA) (Bos d 6) - cow’s milk and beef allergy - CMPA pt. have positive to BSA 0-88% (only 20% have clinical reaction) Curr Opin Allergy Clin Immunol 11: 216-221
    30. 30. Cow’s milk (Bos domesticus) Bovine immunoglobulins (Bos d 7) - in blood, tissue fluid, secretion - seldom cause clinical symptom in CMPA Caseins (Bos d 8) - αs1-caseins, αs2-caseins, β-caseins, κ-caseins - polysensitization to many caseins fraction usually observed (closely epitope or cross- sensitization ) - αs1-caseins major allergen inducing strong immediated or delayed allergic reactions Curr Opin Allergy Clin Immunol 11: 216-221
    31. 31. • Objective : to calculate the frequency of accidental exposure reactions in children allergic to cow’s milk during a 12-month period : to analyze clinical characteristics and circumstances surrounding the reactions : to identify risk factors for severe reactions (J Allergy Clin Immunol 2009;123:883-8.)
    32. 32. • Methods : 88 children allergic to cow’s milk (44 boys; median age, 32.5 months) : cross-sectional study at age >= 18 mo : Systematized questionnaire about accidental exposure (reactions were classified as mild, moderate, and severe) : sIgE to cow’s milk & casein titers were determined periodically as clinical indicated in F/U visit (J Allergy Clin Immunol 2009;123:883-8.)
    33. 33. Severe reaction 15% mo • ResultFive of the 6 children had asthma (J Allergy Clin Immunol 2009;123:883-8.)
    34. 34. Conclusion : Reactions to accidental exposure are frequent in children with cow’s milk allergy. The proportion of severe reactions was 15%. The risk factors for severe reactions included very high levels of specific IgE to cow’s milk and casein and asthma.P, Percentile.Mann-Whitney U test: #/{P 5 .044; #/kP < .01; /P 5 .044; /**P < .01.*P value: comparison between severe AARs versus mild or moderate AARs or no reaction.Fisher test.Mann-Whitney U test.§x2 Test. (J Allergy Clin Immunol 2009;123:883-8.)
    35. 35. fir- Retrospective studies of 52 patients (3 to 114 months) with proven CMA by DBPCFC- All Pt were rechallenge at least once , some were rechallenge 2 or 3 time- 32 (61.5%) patients became tolerant in the analysed time period.- Serum was collected at all time point prior to OFC  analysed for B. Ahrens, et.al, Clinical & Experimental Allergy, 2012 ( ) –
    36. 36. B. Ahrens, et.al, Clinical & Experimental Allergy, 2012 ( ) –
    37. 37. • Result sIgE CM Children with initial sIgE CM below 5.0 kU/L  4 time likely to tolerant 18 33 mo mo B. Ahrens, et.al, Clinical & Experimental Allergy, 2012 ( ) –
    38. 38. • Conclusion• Children became tolerant earlier if their specific IgE-antibody levels against the α-lactalbumin, and β-lactoglobulin(Bos d5.0102), αs1- casein and, κ-casein were low initial low Children with (<0.3ISU/L) sIgE to α lactalbumin,• CM-specific IgE is a good prognostic marker for persistence of CM β lactoglobulin(Bos d 5.0102), κ casein and αs1- casein  7.2, 2.7, 3.8 and 2.7 time likely to tolerant respectively 18 mo B. Ahrens, et.al, Clinical & Experimental Allergy, 2012 ( ) –
    39. 39. Allergen of plant origin
    40. 40. Soy (Glycine max)Allergen component in soy : Gly m 4, 5 and 6 Gly m 4 - PR-10 protein family (Bet v 1 homologue) - pollen-associated soy allergy mainly discribed in adult with mild symptoms (primary sensitization to birch pollen) - cross-reactive to Ara h 8 - In Europe approximately 2/3 of pt. allergic to soy are allergic to peanut Clinical& experimental allergy; 2010: 40: 1442-1460
    41. 41. Soy (Glycine max) Gly m 5 and 6 - most important in primary sensitization to soy protein (via GI tract) esp. in children - sensitization rate to Gly m 5 36% In soy allergic pt. Gly m 6 43% Gly m 5 and Gly m 6 are diagnostic marker for severe allergic reaction to soy Clinical& experimental allergy; 2010: 40: 1442-1460
    42. 42. Paper soy2paper• Aim : to identify relevant soybean allergens and correlate the IgE-binding pattern to clinical characteristics in European patients with confirmed soy allergy• Methods : The IgE reactivity in 30 sera from subjects (Switzerland, Denmark and Italy)— with a positive double- blind, placebo-controlled soybean challenge (n = 25) or a convincing history of anaphylaxis to soy (n = 5) was analyzed by ELISA or CAP-FEIA J Allergy Clin Immunol 2009;123:452-8.
    43. 43. The 2 soybean major storage proteins - Gly m 5 (β-conglycinin : 3 subunits) : α (67kd) : α ‘ (71 kd) :β (50 kd)) - Gly m 6 (glycinin : 5 different subunits) : G1 (A1aB1b, 53.6 kd) : G2 (A2B1a, 52.4 kd) : G3 (A1bB2, 52.2 kd) : G4 (A5A4B3, 61.2 kd) : G5 (A3B4, 55.4 kd)• IgE reactivities major storage Protein (8 subunits) of the proteins were correlated to the clinical characteristics of our patient group to investigate the potential use as biomarkers for severe allergic reactions to soybean. J Allergy Clin Immunol 2009;123:452-8.
    44. 44. Gly m 5 +ve = 13/30 (43%)Gly m 6 +ve = 11/30 (37%) Clinical implications:Gly m 5 ot Gly m 6 +ve =16/30(53%) Component-resolved diagnosis with purified Glym 5 and Glym 6 is potentially applicable for identifying subjects at risk of experiencing severe soy-related allergic reactions. J Allergy Clin Immunol 2009;123:452-8.
    45. 45. Wheat (Triticium aestivum)Tri aA_TI, Tri a 18, Tri a gliadin, Tri a 19 (Ѡ- 5 gliadin)and high molecular weigh glutenin Tri a 14 - Lipid transfer protein - heat resistance and lack of cross-reactivity to pollen - major allergen in pt. living in southern Europe and significant in baker’s asthma Tri a 18 - Hev b 6 homologue (latex component) Clinical& experimental allergy; 2010: 40: 1442-1460
    46. 46. Wheat (Triticium aestivum) Tri a 19 (Ѡ-5 gliadin) - associated with risk of IgE-mediated reaction to wheat - risk of wheat-dependent exercise induce anaphylaxis Clinical& experimental allergy; 2010: 40: 1442-1460
    47. 47. Wheat (Triticium aestivum) Tri aA_TI (alpha-amylase/tyrpsin inhibitor) - wheat allergen in raw and cooked food - play role in wheat-depedent exercise induce anaphylaxis High molecular weigh glutenin - associated with wheat-dependent exercise induce anaphylaxis Tri a gliadin - primary wheat sensitization (low-risk of pollen cross-reactivity) Clinical& experimental allergy; 2010: 40: 1442-1460
    48. 48. • Aim : to examine whether ω-5 gliadin is a clinically relevant allergen in children with hypersensitivity reactions to ingested wheat.• Method : Sera were obtained from 40 children (mean age, 2.5 years; range, 0.7-8.2 years) with suspected wheat allergy (AD a/o GI a/o respiratory symptoms : Wheat allergy Dx with open or DBPC oral wheat challenge. : Wheat ω-5 gliadin was purified by reversed-phase chromatography,and serum IgE antibodies to ω-5 gliadin were measured by ELISA : In vivo reactivity was studied by SPT. : Control sera were obtained from 22 children with no evidence of food allergies J Allergy Clin Immunol 2001;108:634-8
    49. 49. Immediated - 16/19(84 %) detected • Result IgE to Ѡ-5 gliadin - 6/7 SPT +ve to Ѡ-5 gliadin Delayed - not detected IgE to Ѡ-5 gliadin - 2/2 SPT –ve to Ѡ-5 gliadin J Allergy Clin Immunol 2001;108:634-8
    50. 50. Conclusion: The results of this studyshow that ω-5 gliadin is a significantallergen in young children withimmediate allergic reactions toingested wheat. IgE testing with ω-5gliadin could be used to reduce theneed for oral wheat challenges inchildren. J Allergy Clin Immunol 2001;108:634-8
    51. 51. Morita,et al. Allergology International.2009;58:493-498
    52. 52. Peanut (Arachis hypogaea) - most common food associated with fatalallergic reaction in western country, theprevalence also increase in Asia - 13 peanut allergen have been identified - 5 peanut component are clinicallyrelevant and available Ara h1, 2, 3, 6, 8, and 9 Clinical& experimental allergy; 2010: 40: 1442-1460
    53. 53. Peanut (Arachis hypogaea)Ara h 1, 2, and 3 - major peanut allergen (peanut seed storage protein) - associated with primary sensitization - pt. with peanut allergy are sensitized to Ara h 1 35-95% Ara h 2 75-100% Ara h 3 20-55% - stable to heat and digestion  risk of reaction to cooked or roast food Clinical& experimental allergy; 2010: 40: 1442-1460
    54. 54. Peanut (Arachis hypogaea) Ara h 1 - cross-reactive to nut and legume [lentil,pea, and soy(Gly m 5)] Ara h 2 - marker for primary sensitization to peanut and risk marker for severe allergic reaction - cross-reactive to lupine and tree nut (eg. almond and brazil nut) Ara h 3 - cross-reactive to soybean, pea, and tree nuts Clinical& experimental allergy; 2010: 40: 1442-1460
    55. 55. Peanut (Arachis hypogaea) Ara h 6 - high homology to Ara h 2 Ara h 8 - PR-10, Bet V 1 homologue - heat-labile protein cooked food often tolerated - primary sensitization through pollen : birch,cedar - cross-reactive to lupine and soy (Gly m 4) Ara h 9 - Lipid transfer protein (LTP) - associated with severe OAS and systemic reaction - primary sensitization probably due to primary sensitization to peach or other LTP-containing fruits Clinical& experimental allergy; 2010: 40: 1442-1460
    56. 56. • Aim - To establish by oral food challenge the proportion of children with clinical peanut allergy among those considered peanut-sensitized by using skin prick tests and/or IgE measurement - To investigate whether component-resolved diagnostics using microarray could differentiate peanut allergy from tolerance.• Method - The Manchester Asthma and Allergy study  unselected population based birth cohort - participants recruited prenatally and F/U prospectively at age 1, 3, 5 and 8 yr ( questionnaire, SPT, sIgE ) J Allergy Clin Immunol 2010;125:191-7
    57. 57. 13 OFC 85 were sensitized to peanutJ Allergy Clin Immunol 2010;125:191-7
    58. 58. J Allergy Clin Immunol 2010;125:191-7
    59. 59. - Peanut allergy fold change = 6.06  expression level 66.7 time higher than negative control - Peanut tolerant fold change = 0.28  expression level 1.2 time higher than negative control Clinical implications: Measurement of IgE response to major peanut allergen Ara h 2 is more useful in predicting clinical peanut allergy than currently used skin or blood tests based on whole extract.Green : peanut tolerantYellow : peanut allergy J Allergy Clin Immunol 2010;125:191-7
    60. 60. Advantage of CRD• Quantifying IgE antibodies to a single allergen protein component rather than a heterogeneous allergen preparation• Providing a unique component-specific IgE antibody profile of the patient for personalized medical care• Supporting a molecular-level understanding of the patient’s individual constellation of symptoms
    61. 61. Advantage of CRD Advantage of CRD• Better characterize the patient’s sensitization patterns• Better understand the clinical risk for reactions in a patient• Determine the presence of cross-reactivity between allergens• Facilitate food challenge testing with increased knowledge of what to expect• Select appropriate patients for specific immunotherapy and customize treatment
    62. 62. Allergen Components as severity markersPeanut Ara h 1, 2 and 3Soy Gly m 5 and 6Wheat Omega-5-gliadinMilk Bos d 8 (casein)Egg Gal d 1 (ovomucoid)
    63. 63. Important allergenAra h 1, 2, 3, 8 and 9 (peanut)• IgE abs to Ara h 1, 2, 3 and 9 (LTP) are associated withpeanut reactions, which in many cases can be severe.• IgE abs to Ara h 8 (PR-10) are usually associated withmilder, local symptoms such as OAS, originting from birchsensitzation.Ovumucoid (egg white)• IgE abs to ovomucoid are associated with persistent eggallergy and usually neither raw or cooked is tolerated.
    64. 64. Important allergenOmega-5 gliadin (wheat)• IgE abs to omega-5 gliadin (Tri a 19) in adults are associated with arisk of exercise- or NSAIDs-induced reactions in connection withwheat ingestion.• IgE abs to omega-5 gliadin in children are associated with a risk ofimmediate reactions to wheat.Gly m 4,5 and 6 (soy)• Gly m 5 and 6 are associated with clinical reactions to soy.Gly m 5 - Ara h 1 and Gly m 6 - Ara h 3 share homologouesstructures.• IgE abs to Gly m 4 (PR-10) are usually associated with milder, localsymptoms such as OAS, originating from birch sensitzation.

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