1. Allergens Department of Allergology, Clinical Immunology and Internal Diseases Collegium Medicum in Bydgoszcz Ewa Gawronska - Ukleja Ewa Gawronska - Ukleja

2. Definitions and basic knowledge Definitions and basic knowledge Inhalatory allergens Inhalatory allergens Food allergens Food allergens

3. Atopy – definition Atopy is a genetic predisposition toward producing specific IgE as a response to low concentration of substance, usually protein, most commonly manifested as allergic rhinitis, bronchial asthma, atopic dermatitis, or food allergy. Atopy is a genetic predisposition toward producing specific IgE as a response to low concentration of substance, usually protein, most commonly manifested as allergic rhinitis, bronchial asthma, atopic dermatitis, or food allergy.

4. Allergy - definition Allergy is a hypersensitivity reaction initiated by immune mechanisms. Allergy is a hypersensitivity reaction initiated by immune mechanisms.

5. IgE dependent allergy Allergic reactions caused by IgE Allergic reactions caused by IgE

6. Non IgE - mediated allergy Caused by other types of antibodies or lymphocytes Caused by other types of antibodies or lymphocytes

7. Allergen definition An antigenic substance capable of inducing hypersensitivity reaction, by inducing production of antigen specific IgE. Allergens can be protein or glycoprotein.

8. CRD Component resolved diagnosis Component resolved diagnosis The new approach of Molecular Allergology takes the diagnostics one step further by quantifying the allergen specific IgE antibodies to single, pure allergen molecules The new approach of Molecular Allergology takes the diagnostics one step further by quantifying the allergen specific IgE antibodies to single, pure allergen molecules Allergen components are proteins and based on structural similarity these are grouped into different protein families. Depending on the properties of these proteins, sensitization to the components leads to different consequences for the patient. Allergen components are proteins and based on structural similarity these are grouped into different protein families. Depending on the properties of these proteins, sensitization to the components leads to different consequences for the patient.

9. We can divide allergens Based on allergen source (birch, apple, house dust mite and others) Based on allergen source (birch, apple, house dust mite and others) Based on type of protein (tropomyosin, lipogaine, LTP, profilin and others) Based on type of protein (tropomyosin, lipogaine, LTP, profilin and others)

11. Allergens classification Divided into 2 groups: Divided into 2 groups: 1 - Main allergens – sensitizing more then 50 % of patients in certain group for example allergy to house dust mite 1 - Main allergens – sensitizing more then 50 % of patients in certain group for example allergy to house dust mite 2 - Week allergens – week sensitizing ability 2 - Week allergens – week sensitizing ability

12. Allergen contains epitopes. An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that recognizes the epitope is called a paratope. Although epitopes are usually thought to be derived from non-self proteins, sequences derived from the host that can be recognized are also classified as epitopes. Allergen contains epitopes. An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that recognizes the epitope is called a paratope. Although epitopes are usually thought to be derived from non-self proteins, sequences derived from the host that can be recognized are also classified as epitopes.

13. Classification of inhalatory allergens Plant allergens Plant allergens House dust mite House dust mite Moulds Moulds Animals dander Animals dander Cockroach Cockroach Feather Feather Daphnia Daphnia

14. In Poland there are 20 species of plants, which can sensitize Allergen is not the whole grain, but only its halo. Allergen is not the whole grain, but only its halo. Grass Most important : Timothy, Rispengras, Honiggras Most important : Timothy, Rispengras, Honiggras Flowering period – from the beginning of May to the half of July; Flowering period – from the beginning of May to the half of July; Grain size - 25 to 35 um. Grain size - 25 to 35 um. Pollen amount : in 1 m3 - 280 mln. Pollen amount : in 1 m3 - 280 mln.

15. Artemisia vulgaris Artemisia vulgaris Flowering period – from the beginning of September to the half of September Flowering period – from the beginning of September to the half of September Grain size - 20 to 25 um. Grain size - 20 to 25 um. 20% of patients have allergy only to weeds, the rest have also allergy to grass 20% of patients have allergy only to weeds, the rest have also allergy to grassWeeds

16. Ragweed (Ambrosia) - the strongest of weed allergens in North America In Europe- Hungary, Czech Republic, Slovakia, Ukraine, the south of France In Europe- Hungary, Czech Republic, Slovakia, Ukraine, the south of France People with allergy to weeds should be informed about it, when they are traveling to one of those countries. People with allergy to weeds should be informed about it, when they are traveling to one of those countries.

17. Main tree allergens in Poland - birch, hazel, alder Main tree allergens in Poland - birch, hazel, alder Flowering period – from the end of February to the end of April Flowering period – from the end of February to the end of April Grain size – above 30 um. Grain size – above 30 um. Trees

18. Poplar Symptoms are rare Symptoms are rare Flowering period – from march to April Flowering period – from march to April Grain size – 35 um. Grain size – 35 um.

19. Christmas tree syndrome Pine tree, spruce, Abies alba, larch - sensitize rare, but some studies describe „Christmas tree syndrome” Pine tree, spruce, Abies alba, larch - sensitize rare, but some studies describe „Christmas tree syndrome”

20. Cross – allergy ( cross-reactivity, cross-sensivity) -Allergy to the same epitops of different allergens -It means that, IgE antibody produced in atopic patient organism can react with allergens which did not induced they production.

21. Cross – allergy Birch pollen – apple, potato, hazel nuts, carrot, tomato Birch pollen – apple, potato, hazel nuts, carrot, tomato Grass pollen – peanuts, soya bean, poteto Grass pollen – peanuts, soya bean, poteto Weed pollen - celery Weed pollen - celery

22. House dust mite Dermatophagoides pteronissinus Dermatophagoides pteronissinus Dermatophagoides farinae Dermatophagoides farinae Glycophagus domesticus Glycophagus domesticus Euroglyphys mainei Euroglyphys mainei Acarus siro Acarus siro

23. They are arachnid, about 0.25mm (0.01 inch) long. They are invisible to the naked eyes. They are arachnid, about 0.25mm (0.01 inch) long. They are invisible to the naked eyes. Rapid reproduction cycle: It takes about a month for a dust mite egg to hatch and the mite to mature to an adult. An adult female mite may live another month and lay about 50 (some authors say 200) eggs in skin- ladden house dust. Can survive in temperatures above 15°C and in a relative humidity above 50%. The ideal temperature is around 25°C. The ideal relative humidity is between 75 - 80%. Do not need to drink to satisfy their thirst. They absorb water directly from the air through special glands in their skin. Rapid reproduction cycle: It takes about a month for a dust mite egg to hatch and the mite to mature to an adult. An adult female mite may live another month and lay about 50 (some authors say 200) eggs in skin- ladden house dust. Can survive in temperatures above 15°C and in a relative humidity above 50%. The ideal temperature is around 25°C. The ideal relative humidity is between 75 - 80%. Do not need to drink to satisfy their thirst. They absorb water directly from the air through special glands in their skin. Dust mites feed on organic detritus such as flakes of shed human skin and flourish in the stable environment of dwellings. Dust mites feed on organic detritus such as flakes of shed human skin and flourish in the stable environment of dwellings.

24. Dermatophagoides pteronyssinus is the most popular in Europe (87% - 95% of mite in houses in central Europe) Dermatophagoides pteronyssinus is the most popular in Europe (87% - 95% of mite in houses in central Europe)

25. 100 mites on 1 gram of dust are enough to sensitized 100 mites on 1 gram of dust are enough to sensitized House dust mite can be killed by hot water at a temperature above 55°C (130°F). Therefore it is advisable to use bedding items that are washable in water. The pillow, mattress and duvet can be protected by zipped and tightly-woven cotton bedding covers that can prevent dust mites from passing through. House dust mite can be killed by hot water at a temperature above 55°C (130°F). Therefore it is advisable to use bedding items that are washable in water. The pillow, mattress and duvet can be protected by zipped and tightly-woven cotton bedding covers that can prevent dust mites from passing through.

26. Moulds (Mold) allergens Moulds are parasite or saprophyte. There are 120 000 of known species of molds Moulds are parasite or saprophyte. There are 120 000 of known species of molds Humidity is 70% Humidity is 70% Spore size 2-5 µm Spore size 2-5 µm

27. Mold spore Concentration of mold spores, which causes allergy symptoms in patients with hypersensitivity, is 2800 spores of Cladosporium in m 3 (threshold value). Concentration of mold spores, which causes allergy symptoms in patients with hypersensitivity, is 2800 spores of Cladosporium in m 3 (threshold value).

28. Mold allergens New research technique enabled us to describe main allergens, which react with IgE antibody in blood serum. New research technique enabled us to describe main allergens, which react with IgE antibody in blood serum. Aspergillus : Asp J 1, Asp J 2, Asp J 3 i Asp J 12, Aspergillus : Asp J 1, Asp J 2, Asp J 3 i Asp J 12, Alternaria: Alta 1, Alta 2, Alta 3, Alta 6, Alta 7, Alta 10 Alternaria: Alta 1, Alta 2, Alta 3, Alta 6, Alta 7, Alta 10 Cladosporium ( Cla h 1, Cla h 2, Cla h 3) Cladosporium ( Cla h 1, Cla h 2, Cla h 3)

29. Seasonal inhalatory allergy Summer, autumn -Alternaria-Cladosporium

30. Perennial inhalatory allergy - Aspergillus - Penicillium

31. Food allergy Yeast Yeast Blue cheese, cammembert Blue cheese, cammembert Vine Vine Bear Bear Champagne Champagne

32. Food allergy Mold on food Mold on food Greengrocery Greengrocery Fruits Fruits

33. Asthma & allergy to molds Allergy to Alternaria alternata is a risk factor of sever asthma!!! Allergy to Alternaria alternata is a risk factor of sever asthma!!!

34. Treatment 1. Avoiding exposition 2. Immunotherapy 3. Symptoms management

35. Avoiding exposition to allergen Mold in the home can usually be found in damp, dark or steam filled areas e.g. bathroom or kitchen, cluttered storage areas, recently flooded areas, basement areas, plumbing spaces, areas with poor ventilation and outdoors in humid environment.

36. Allergy to cat The main cat allergen is Fel d 1 – a glycoprotein. This molecules can fly in the air for many hours. They can be transported on clothes, and appear in places without cats. The main cat allergen is Fel d 1 – a glycoprotein. This molecules can fly in the air for many hours. They can be transported on clothes, and appear in places without cats. The biggest source of allergens are saliva, sebaceous glands and anal glands The biggest source of allergens are saliva, sebaceous glands and anal glands Some cats are week, some are strong producers of allergens. Some cats are week, some are strong producers of allergens. There is about 2-30 % of people with There is about 2-30 % of people with allergy to cats in population.

37. Dog allergens The main dog allergen (Can f 1) occurs in dogs dander, also in saliva, urine, and skin. Sometimes it can fly in the air. Patients with allergy to cats and dogs often have hypersensitivity to other animals. The main dog allergen (Can f 1) occurs in dogs dander, also in saliva, urine, and skin. Sometimes it can fly in the air. Patients with allergy to cats and dogs often have hypersensitivity to other animals.

38. Cattle allergens Cattle allergens have week sensitizing ability. Allergy to cows dander can occur in farm workers. Cattle allergens have week sensitizing ability. Allergy to cows dander can occur in farm workers.

39. Horse allergens Horse allergens easily spread in the air, they are in dander, urine and sweat. Allergy symptoms appear during contact of sensitized person with animal. Horse allergens easily spread in the air, they are in dander, urine and sweat. Allergy symptoms appear during contact of sensitized person with animal.

40. Feather Feathers of many birds are inhalatory allergens, e.g. : hen, duck, turkey, goose, also canary and parrot Feathers of many birds are inhalatory allergens, e.g. : hen, duck, turkey, goose, also canary and parrot Feather of different species have separate allergens. But there exist probably one allergen, which is the same in many different species. Feather of different species have separate allergens. But there exist probably one allergen, which is the same in many different species.

41. Food allergens In 1995 „Food and Agriculture Organization” experts - from USA, for the first time used the term : „the big 8 food allergens” In 1995 „Food and Agriculture Organization” experts - from USA, for the first time used the term : „the big 8 food allergens” Milk Milk Eggs Eggs Peanuts Peanuts Nuts Nuts Seafood Seafood Shellfish Shellfish Soy Soy Wheat. Wheat.

42. Food allergens Food allergens are soluble in water Food allergens are soluble in water Cooking can reduced sensitizing ability of allergen. Cooking can reduced sensitizing ability of allergen. In infants the most frequent allergy is allergy to cows milk and egg In infants the most frequent allergy is allergy to cows milk and egg In adults peanuts, fishes, fruits and vegetables. In adults peanuts, fishes, fruits and vegetables.

43. Egg white allergens Egg white contains many allergens, nowadays we know about 23, but 4 of them are main: Gal d 1, Gal d 2, Gal d 3, Gal d 4. Egg white contains water(88%) and proteins (10%), which are the most important source of allergens. Egg white contains many allergens, nowadays we know about 23, but 4 of them are main: Gal d 1, Gal d 2, Gal d 3, Gal d 4. Egg white contains water(88%) and proteins (10%), which are the most important source of allergens.

45. Milk allergens In Europe, milk allergy occurs in 1,9 to 2,8% of children below 2. It contains about 30 sensitizing proteins. The strongest are: In Europe, milk allergy occurs in 1,9 to 2,8% of children below 2. It contains about 30 sensitizing proteins. The strongest are: - β - laktoglobulin – the most frequent (80%) - β - laktoglobulin – the most frequent (80%) - λ - laktoalbumin –sensitizing 50% of patients with milk allergy - λ - laktoalbumin –sensitizing 50% of patients with milk allergy - albumin of cattle serum –30% - albumin of cattle serum –30% - casein - casein

46. Casein which is the most important cheese allergen, is sensitizing about 60% of patients and is the most temperature resistant protein in milk. Casein which is the most important cheese allergen, is sensitizing about 60% of patients and is the most temperature resistant protein in milk. Goat and sheep milk has many mutual features, their proteins could induce cross- reactivity. Goat and sheep milk has many mutual features, their proteins could induce cross- reactivity. Milk allergens

47. Fish allergens Fish contain strong allergens, so allergy to fish is very common in children and adults. Fish contain strong allergens, so allergy to fish is very common in children and adults. They contain 2 kinds of allergens : They contain 2 kinds of allergens : 1.Mutual for all species 2.Specific for each species Fish allergens are temperature resistant. Fish allergens are temperature resistant.

48. Epidemiology  Allergy to fish is one of the most frequent (in USA about 10% of patients with food allergy, are allergic to fish)  This fact is nowadays more and more meaningful, because the consumption of fish is increasing  Fish more often sensitize children and this allergy does not recede with age.

49. Symptoms can appear not only after consumption, but also in the inhalatory way (fumes of fried or cooked fish) and during skin contact. Symptoms can appear not only after consumption, but also in the inhalatory way (fumes of fried or cooked fish) and during skin contact.

50. Attention !!! Fish contains histamine, so after their consumption, patients can have a toxic reaction. Fish contains histamine, so after their consumption, patients can have a toxic reaction.

51. Aniskas simplex – fish parasite  Allergen hidden in fish  Cross reactivity with Ascaris lumbricoides and Echinococcu granulosus

52. In Mediterranean countries, where „sea food” is very popular (especially oysters, snails, bivalvias, squids), allergy symptoms after eating sea food can be often found. In Mediterranean countries, where „sea food” is very popular (especially oysters, snails, bivalvias, squids), allergy symptoms after eating sea food can be often found. Sea food

53. Shrimp allergens Tropomyosin has been demonstrated as a major allergen in shrimp in several studies. Argininkinase (mv 40 kD) and an unidentified component of 16.5 kD have also been discussed and might be additional cross- reacting allergens playing a role in allergy to crustaceans Tropomyosin has been demonstrated as a major allergen in shrimp in several studies. Argininkinase (mv 40 kD) and an unidentified component of 16.5 kD have also been discussed and might be additional cross- reacting allergens playing a role in allergy to crustaceans Of these allergens, a number have been characterized.Met e1 (Metapenaeus ensis), Pen a1 (Penaeus aztecus), Pen i1 (Penaeus indicus) and Pen m1 (Penaeus monodon) from Tropomyosin. Of these allergens, a number have been characterized.Met e1 (Metapenaeus ensis), Pen a1 (Penaeus aztecus), Pen i1 (Penaeus indicus) and Pen m1 (Penaeus monodon) from Tropomyosin. Lit v2 (Litopenaeus vannamei) and Pen m2 (Penaeus monodon) from Argininkinase. Lit v2 (Litopenaeus vannamei) and Pen m2 (Penaeus monodon) from Argininkinase.

54. Cross-reactivity due to tropomyosin has been shown between crustaceans, molluscs and non- edible arthropods such as insects (cockroach, chironomides) arachnids (house dust mite – tropomyosine Der p 10 ) Cross-reactivity due to tropomyosin has been shown between crustaceans, molluscs and non- edible arthropods such as insects (cockroach, chironomides) arachnids (house dust mite – tropomyosine Der p 10 )

55. Meat allergens Beef and pork are hardly ever sensitizing. We can find hypersensitivity to meat in children with allergy to milk. Beef and pork are hardly ever sensitizing. We can find hypersensitivity to meat in children with allergy to milk.

56. Grain allergens Wheat flour is one of basic comestible product. In adults, allergy to flour occurs in bakers with asthma. Wheat flour is one of basic comestible product. In adults, allergy to flour occurs in bakers with asthma. In infants allergy to flour is 3 of the most frequent allergies. The main antigen is inhibitor λ – amylase. In infants allergy to flour is 3 of the most frequent allergies. The main antigen is inhibitor λ – amylase. Rye and barley flour has similar sensitizing features. Rice sensitize unusually. Rye and barley flour has similar sensitizing features. Rice sensitize unusually.

58. Soya bean allergens Soya bean – is a very important source of proteins, which are strong allergens. Soya bean – is a very important source of proteins, which are strong allergens. Researches shows that 50 % of children with milk allergy have also allergy to soya beans. Researches shows that 50 % of children with milk allergy have also allergy to soya beans. Soya beans contains 80% – 90% globulin. Main soya allergens are Gly 1 A i Gly 1 B. Soya beans contains 80% – 90% globulin. Main soya allergens are Gly 1 A i Gly 1 B.

59. Potato allergens Potato has strong sensitizing ability, both raw and cooked. Potato has strong sensitizing ability, both raw and cooked. Cooked potatoes have weaker sensitizing ability, because they have got more temperature sensitive allergens. Cooked potatoes have weaker sensitizing ability, because they have got more temperature sensitive allergens. The main antigen is patatyna. The main antigen is patatyna.

60. Tomato Tomato is often sensitizing, Tomato is often sensitizing, Mature vegetable contains glycoprotein. Mature vegetable contains glycoprotein. It is worth to remember that there is a cross reactivity between tomato and latex. It is worth to remember that there is a cross reactivity between tomato and latex.

61. Celery Allergy to celery coexist with allergy to Artemisia. Main celery allergens are: Api g 2, Api g 3. After celery consumption in patients, strong reaction can appear: anaphylactic shock or asthma attack. Allergy to celery coexist with allergy to Artemisia. Main celery allergens are: Api g 2, Api g 3. After celery consumption in patients, strong reaction can appear: anaphylactic shock or asthma attack.

62. Carrot Allergy to carrot sometimes coexist with allergy to other fruits or vegetables. Allergy to carrot sometimes coexist with allergy to other fruits or vegetables. Researches show exist of mutual epitops in carrot, celery and dill. Researches show exist of mutual epitops in carrot, celery and dill.

63. Apple This allergy is often. This allergy is often. Apple allergens contain protein Mal d 1, which is very similar to birch protein Bet v 1. This is the reason why allergy symptoms (oral allergy syndrome) appear in patients with allergy to birch after apple consumption. Apple allergens contain protein Mal d 1, which is very similar to birch protein Bet v 1. This is the reason why allergy symptoms (oral allergy syndrome) appear in patients with allergy to birch after apple consumption. Different apple antigen has the mutual epitops with carrot. Different apple antigen has the mutual epitops with carrot.

64. Banana Allergy to banana can appear in infants. Allergy to banana can appear in infants. Contains glycoprotein and is rich in serotonin Contains glycoprotein and is rich in serotonin It is worth to remember that there is a cross reactivity between banana and latex. It is worth to remember that there is a cross reactivity between banana and latex. Allergy to banana sometimes coexist with allergy to kiwi and avocado. Allergy to banana sometimes coexist with allergy to kiwi and avocado.

65. Allergy to peanuts They contains a lot of proteins. They contains a lot of proteins. They are used in many dishes, in form of the whole nut or peanut butter. They are used in many dishes, in form of the whole nut or peanut butter. Peanut oil should not contain protein so it is not sensitizing. Peanut oil should not contain protein so it is not sensitizing. Allergens are temperature resistant Allergens are temperature resistant

66. Epidemiology  The most significant problem in USA  It is estimated to affect 0.6-2% of the population  In West Europe allergy to peanuts is 25% of food allergy

67. Chemical structure of nut proteins  Albumins (Soluble in water) and globulins (Soluble in salt)  Allergens are 7 proteins, main of them are Arah1 i Arah2  Arah1 is totally resistant for high temperature  In 80% of patients allergy lasts for a life time.

68. Problems with allergy to nuts  Very dangerous! Nut allergens are very strong, not only the whole nut, but also dust that is created around them and even the aroma.  The most severe allergies in general can result in anaphylaxis. We cannot predict the severness of symptoms.  The smell of nuts is enough for patient with peanut allergy to develop a symptoms.  Nut allergens are in many dishes (halvah, chili souse, Chinese food).  We can find them not only in food, but also : air condition, cosmetics and drugs.

69.  Even after 10 years of avoiding nut allergens, skin prick tests in patients are positive  Kiss of a person, who ate peanuts or used lipstick with peanut oil is enough to release allergy symptoms.  In 1999 one bite of sandwich with nut butter killed 21 year old Ross Baillie – great British athlete.  In 1988 there was a case report about anaphylactic reaction in inhalatory way in plane passenger. Problems with allergy to nuts

70. The end of allergy to nuts?  Scientists elaborate a special kind of fermentation which decreases to 70 % the amount of protein which causes allergy (Arah1 and Arah2). This fermentation does not change the taste of nuts.  To prevent allergy to peanuts, researchers compile vaccine on a base of modified nut proteins

71. Prevention  Carefully reading label of groceries products  Information about allergy ( e.g. bracelet with information in children)  Avoid nuts in pregnant and breast feeding women  Avoid nuts in children below 3

72. Peanuts are dangerous not only as allergens Incorrectly preserve nuts contain large amount of aflatoxins, which are a risk factor of liver cancer Remember

73. Thank You for your attention !!!!!!!