Precision medicine allergy immunoassay methods for assessing immunoglobulin E sensitization to aeroallergen molecules

Table 1 Classification of immunoassays used for the detection of specific immunoglobulin E against allergen components[9,40,41]

Type of immunoassay	Description
Singleplex	Detect specific IgE against a single allergen component
Multiparameter	Detect specific IgE against a few allergen components at once (usually - 10)
Multiplex	Detect simultaneously specific IgE against many different allergen components (> 100)

IgE: Immunoglobulin E.

Table 2 Allergen molecules of house dust and storage mites origin¹ used in singleplex and multiplex immunoassays[9,74,102,103]

Allergen molecule	Biological function, comments, CR
House dust mites (Dermatophagoides pteronyssinus, Dermatophagoides farinae, Euroglyphus maynei, Blomia tropicalis)
nDer p 1 rDer f 1	Cysteine-protease, cleavage of regulatory IgE synthesis CD23, CD25 Midgut (colon, intercolon, postcolon) and mite fecal pellets Group 1 major mite allergen, CR with nDer f 1
rDer p 2 nDer p 2 rEur m 2	Functional homologue of adaptor MD-2, TLR4 coreceptor Midgut (ventriculus, paired caeca), male reproductive tract, fecal pellets Group 2 major mite allergen, NPC2 family, CR Der p 2, Der f 2, homologue Lep d 2
rDer p 4	Group 4 major mite allergen
rDer p 5	Group 5 major mite allergen, homologue rBlo t 5
rDer p 7	LPS-binding protein, stimulation TLR2, group 7 mite allergen
rDer p 9	Serine protease, group 9 mite allergen
rDer p 10	Invertebrate panallergen tropomyosin muscular protein from mite locomotory muscles Group 10 CR mite allergen, invertebrate panallergen CR rAni s 3, nBla g 7, rPer a 7, rPen a 1, Pen m 1, Lit v 1, Hel as 1, Ven g 1, Uro du 1 Involved in house dust mites-crustaceans-mollusks syndrome
rDer p 11	Paramyosin, major allergen
rDer p 14	Apolipophorin-like allergen, lipid transport particles
rDer p 15 rDer p 18	Chitinase-like allergens
nDer p 20	Arginine kinase, CR shrimp Penaeus monodon Pen m 2
rDer p 21	Group 21 mite allergen, gut and fecal particles
rDer p 23	Peritrophin-like protein (8 kDa), group 23 mite major allergen Peritrophic lining of mite gut, fecal pellets
Storage mites (Glycyphagus domesticus, etc.)
rGly d 2	Group 2 mite allergens, NPC2 protein CR Lep d 2, homologue Der p 2 (limited CR)

¹n: Native purified;

r: Recombinant; Per a: Cockroach periplaneta americana allergen molecule; Mite Dermatophagoides pteronyssinus (Der p), Dermatophagoides farinae (Der f), Glycyphagus domesticus (Gly d), Lepidoglyphus destructor (Lep d), Blomia tropicalis (Blo t) allergen molecules; Nematode Anisakis simplex (Ani s) allergen molecule; Shrimp Penaeus aztecus (Pen a), Penaeus monodon (Pen m), Litopenaeus vannamei (Lit v 1), clam Venus gallina (Ven g), squid Uroteuthis duvauceli (Uro du) and snail Helix aspersa (Hel as) allergen molecules; CD: Cluster of Differentiation; CR: Cross-reactivity; LPS: Lipopolysaccharide; NPC2: Niemann-Pick type C2 protein; TLR: Toll-like receptor.

Table 3 Allergen molecules of domestic insect pest origin¹ used in singleplex and multiplex immunoassays[9,74,104]

Allergen molecule	Biological function, comments, CR
Cockroaches (Blattella germanica, Periplaneta americana)
rBla g 1	Midgut microvilli protein-homolog CR Per a 1 (group 1),
	secreted in the digestive system and excreted in fecal particles,
	concentration in feces of adult females higher vs adult males and nymphs
rBla g 2	Unusual inactive aspartic protease with strong allergenic properties
	Digestive organs (esophagus, gut and proventriculus) and fecal particles
rBla g 4	Insect calycin lipocalin, calcium binding protein,
	binds tyramine/octopamine with role in reproduction of insects
rBla g 5	GST
	Involved in detoxification of toxic compounds role in insecticide resistance
rPer a 7	Invertebrate tropomyosin, muscle contraction protein,
	invertebrate panallergen CR Bla g 7, locomotor insect body parts

¹n: Native purified;

r: Recombinant; Cockroaches Blattella germanica (Bla g) and Periplaneta americana (Per a) allergen molecules; CR: Cross-reactivity; GST: Glutathione S-transferase.

Table 4 Allergen molecules of mammalian pet/pest origin¹ used in singleplex and multiplex immunoassays[9,74,105]

Allergen molecule	Biological function, comments, CR
Mammalian pets (Felis domesticus, Canis familiaris)
rFel d 1	Secretoglobin, major cat allergen, species-specific,
	sebaceous glands (testosterone influenced, production higher in males)
	Dispersed by dander (regardless of race)
	Sublingual salivary glands (saliva), lacrimal and anal glands
rFel d 2	Feline serum albumin in cat serum, dander, saliva, minor allergen
	CR nBos d 6 BSA
	CR Sus s 1 serum albumin: pork-cat syndrome involvement
rFel d 4	Feline lipocalin in cat serum, dander, saliva
	CR moderate risk with lipocalins rEqu c 1 and Can f 6
rCan f 1	Non-CR lipocalin from sublingual salivary glands (saliva) and dander
	Major allergen not influenced by hair length or hormonal status
rCan f 2	Non-CR lipocalin, major allergen in dander and saliva
	Together with rCan f 1 and rCan f 5 are species-specific markers of sensitization
nCan f 3	Canine serum albumin, found in serum, dander, saliva
	High CR with other serum albumins: rFel d 2, nEqu c 3
rCan f 4	Non-CR lipocalin major allergens
rCan f 6	(both Can f 4 and Can f 6 are dog lipocalins)
rCan f 5	Dog prostatic kallikrein, an arginine esterase,
	major allergen in male urine, dander
House mouse (Mus musculus)
nMus m 1	Lipocalin-odorant binding rodent family of MUPs

¹n: Native purified;

r: Recombinant; Cat Felis domesticus (Fel d) and dog Canis familiaris (Can f) allergen molecules; Horse Equus caballus (Equ c), cow Bos domesticus (Bos d) and domestic pig Sus scrofa (Sus s) allergen molecules; BSA: Bovine serum albumin; CR: Cross-reactivity; MUPs: Major urinary proteins.

Table 5 Allergen molecules of fungal origin¹ used in singleplex and multiplex immunoassays[9,74,106-108]

Allergen molecule	Biological function, comments, CR
Ascomycetes fungi (Alternaria alternata, Cladosporium herbarum, Aspergillus fumigatus)
rAlt a 1	Fungal beta-barrel protein, detected in spores before germination
	Involvement in Alternaria-spinach syndrome
rAlt a 6	Fungal enolase, panallergen CR Cla h 6, Asp f 22, Pen c 22
rCla h 8	Fungal mannitol dehydrogenase, major allergen, CR Alt a 8
rAsp f 1	Fungal ribotoxin, specific major allergen, member of the mitogillin family
	Not present in spores, but produced after germination and growth
	Genuine exposure and IgE sensitization to A. fumigatus germinated in the respiratory tract
rAsp f 2	Species-specific allergen component, with high frequency of sensitization among patients affected by ABPA
rAsp f 3 rAsp f 4	Fungal peroxisomal protein, CR Pen c 3
	Fungal protein, highly specific allergen
	With high frequency of sensitization among ABPA patients
rAsp f 6	Fungal Mn-SOD, CR Alt a 14, Mala s 11

¹n: Native purified;

r: Recombinant; Fungi Alternaria alternata (Alt a), Cladosporium herbarum (Cla h), Aspergillus fumigatus (Asp f), Penicillium citrinum (Pen c), Malassezia sympodialis (Mala s) allergen molecules; ABPA: Allergic bronchopulmonary aspergillosis; CR: Cross-reactivity; Mn-SOD: Mn superoxide dismutase.

Table 6 Main species-specific allergen molecules of pollen origin¹ used in singleplex and multiplex immunoassays[9,74,93]

Plant source	Allergenic molecule	Biological function, comments
Specific allergen components of tree pollen origin (birch Betula verrucosa, olive tree Olea europaea, plane tree Platanus acerifolia, cypress Cupressus arizonica, etc.)
Betulaceae family	rBet v 1	PR-10 protein, heat sensitive
		CR with Bet v 1-like proteins Cor a 1, Mal d 1
		Involved in birch-hazelnuts-Rosaceae fruit syndrome
Oleaceae family	rOle e 1	Trypsin inhibitor
Platanaceae family	rPla a 1	Invertase inhibitor
	nPla a 2	Polygalacturonase
Cupressaceae family	nCup a 1	Pectate lyase
Specific allergen components of grass pollen origin (Timothy grass: Phleum pratense, Bermuda grass: Cynodon dactylon, etc.)
Poaceae family	rPhl p 1	Beta-expansin
Pooideae subfamily	rPhl p 5	Ribonuclease;
		other allergen molecules: rPhl p 2, rPhl p 6
Chloridoideae subfamily nCyn d 1 Beta-expansin
Specific allergen components of weed pollen origin (mugwort Artemisia vulgaris, ragweed Ambrosia artemisiifolia, Pellitory Parietaria judaica, plantain Plantago lanceolata, saltwort Salsola kali, goosefoot Chenopodium album, etc.)
Asteraceae family	nArt v 1	Defensin-like protein
	nAmb a 1	Pectat lyase, CR Art v 6
Urticaceae family	rPar j 2	Lipid transfer protein
Plantaginaceae family	rPla l 1	Trypsin inhibitor Ole e 1-like protein
Amaranthaceae/Chenopodiaceae family	nSal k 1	Pectin methylesterase
	rChe a 1	Trypsin inhibitor
		Ole e 1-like protein

¹n: Native purified;

r: Recombinant; Fruit hazelnut Corylus avellana (Cor a) and apple Malus domestica (Mal d) allergen molecules; Pollen Betula verrucosa (Bet v), Olea europaea (Ole e), Platanus acerifolia (Pla a), Cupressus arizonica (Cup a), Phleum pratense (Phl p), Cynodon dactylon (Cyn d), Artemisia vulgaris (Art v), Ambrosia artemisiifolia (Amb a), Parietaria judaica (Par j), Plantago lanceolata (Pla l), Salsola kali (Sal k), Chenopodium album (Che a) allergen molecules; PR: Pathogenesis-related plant proteins; CR: Cross-reactivity.

Table 7 Cross-reactive allergen components of pollen origin¹ used in singleplex and multiplex immunoassays[9,74]

Allergen molecule	Biological function, comments, CR
Polcalcins
rPhl p 7	Calcium-binding protein, polcalcin biomarker
	Minor allergen CR with other polcalcins contained in pollen grains:
	grasses: Pooideae and non-Pooideae, e.g., Bermuda grass (Cyn d 7)
	trees: e.g., birch (Bet v 3), alder (Aln g 4), olive (Ole e 3), juniper (Jun o 4)
	weeds: e.g., mugwort (Art v 5), short ragweed (Amb a 10)
rBet v 4	Polcalcin, which contains only two calcium-binding domains
	(vs Bet v 3, which contains three calcium-binding domains)
	Polcalcin biomarker
Non-specific lipid transfer proteins
nArt v 3	PR-14 protein, CR with peach Pru p 3 from, hazelnut Cor a 8
	Involved in mugwort-peach association, Asteraceae-hazelnut association
nOle e 7	PR-14 protein, CR with peach Pru p 3, pear Pyr c 3, melon Cuc m LTP, kiwifruit Act d 10,
	Involved in olive pollen-fruit syndrome
rPla a 3	PR-14 protein, CR with hazelnut Cor a 8, banana Mus a 3, celery Api g 2
	Involved in Platanus pollen-fruit/vegetables association
Profilins
rPhl p 12	Plant panallergen actin-binding protein (cytoskeleton dynamics)
	Profilin biomarker with great sequence identity with other profilins
	CR with profilins from:
	grass pollen: Pooideae and non-Pooideae, e.g., Bermuda grass (Cyn d 12)
	tree pollen: i.e., birch (Bet v 2), olive (Ole e 2), date palm (Pho d 2)
	weed pollen: i.e., ragweed (Amb a 8) and mugwort (Art v 4); sunflower (Hel a 2)
	CR with profilins in latex (Hev b 8) and exotic fruits, involved in pollen-latex-fruit syndrome:
	profilins from ananas (Ana c 1), banana (Mus xp 1), kiwi (Act d 9) and olive pollen (Ole e 2)
	CR with profilins from various plant foods:
	profilin Art v 4 CR with Dau c 4, Api g 4, involvement in celery-mugwort-spice syndrome
	profilin Amb a 8 CR with Cuc m 2, Mus xp 1, involved in ragweed-melon-banana association
rBet v 2	Cross-reactive biomarker, important for the profilin group
	CR profilins in Apiaceae (Dau c 4, Api g 4)
	Involvement in birch-Apiaceae vegetables association

¹n: Native purified;

r: Recombinant; Fruit hazelnut Corylus avellana (Cor a), Prunus persica (Pru p), Pyrus communis (Pyr c), Cucumis melo (Cuc m), Actinidia deliciosa (Act d), Musa acuminata (Mus a), Ananas comosus (Ana c) allergen molecules; Latex Hevea brasiliensis (Hev b) allergen molecule; Pollen Betula verrucosa (Bet v), Alnus glutinosa (Aln g), Olea europaea (Ole e), Platanus acerifolia (Pla a), Juniperus oxycedrus (Jun o), Phoenix dactylifera (Pho d), Phleum pratense (Phl p), Cynodon dactylon (Cyn d), Artemisia vulgaris (Art v), Ambrosia artemisiifolia (Amb a), Helianthus annuus (Hel a) allergen molecules; Vegetables Apium graveolans (Api g), Daucus carota (Dau c) allergen molecules; CR: Cross-reactivity; PR: Pathogenesis-related plant proteins.