36:
2949:
580:, a biotech company based in Houston, Texas, proposed in 1987 that by targeting membrane-bound IgE (mIgE) on B lymphoblast and memory B cells, those cells can be lysed or down-regulated, thus achieving the inhibition of the production of antigen-specific IgE and hence a shift of immune balance toward non-IgE mechanisms. Two approaches targeting the IgE pathway were evolved and both are in active development. In the first approach, the
28:
2961:
20:
592:) recognises IgE not bound to its receptors and is used to neutralise or mop-up existing IgE and prevent it from binding to the receptors on mast cells and basophils. Xolair has been approved in many countries for treating severe, persistent allergic asthma. It has also been approved in March 2014 in the European Union and the U. S. for treating
404:(for allergies) might have some undesirable side effects. However, a recent study, which was performed based on pooled analysis using comprehensive data from 67 phase I to IV clinical trials of omalizumab in various indications, concluded that a causal relationship between omalizumab therapy and malignancy is unlikely.
600:. In the second approach, antibodies specific for a domain of 52 amino acid residues, referred to as CĪµmX or M1ā (M1 prime), present only on human mIgE on B cells and not on free, soluble IgE, have been prepared and are under clinical development for the treatment of allergy and asthma. An anti-M1ā humanized antibody,
375:
venoms. The authors concluded that "a small dose of bee venom conferred immunity to a much larger, fatal dose" and "this kind of venom-specific, IgE-associated, adaptive immune response developed, at least in evolutionary terms, to protect the host against potentially toxic amounts of venom, such as
311:
or natural helper cells). Basophils share a common haemopoietic progenitor with mast cells; upon the cross-linking of their surface bound IgE by antigens, also release type 2 cytokines, including IL-4 and IL-13, and other inflammatory mediators. The low-affinity receptor (FcĪµRII) is always expressed
611:
determined the structure of IgE. Understanding of this structure (which is atypical of other isotypes in that it is highly bent and asymmetric) and of the interaction of IgE with receptor FcĪµRI will enable development of a new generation of allergy drugs that seek to interfere with the IgE-receptor
535:
Diagnosis of allergy is most often done by reviewing a person's medical history and finding a positive result for the presence of allergen specific IgE when conducting a skin or blood test. Specific IgE testing is the proven test for allergy detection; evidence does not show that indiscriminate IgE
1969:
Cox L, Williams B, Sicherer S, Oppenheimer J, Sher L, Hamilton R, Golden D (December 2008). "Pearls and pitfalls of allergy diagnostic testing: report from the
American College of Allergy, Asthma and Immunology/American Academy of Allergy, Asthma and Immunology Specific IgE Test Task Force".
575:
IgE, the IgE synthesis pathway, and the IgE-mediated allergic/inflammatory pathway are all important targets in intervening with the pathological processes of allergy, asthma, and other IgE-mediated diseases. The B lymphocyte differentiation and maturation pathway that eventually generate
333:
The IgE isotype has co-evolved with basophils and mast cells in the defence against parasites like helminths (like
Schistosoma) but may be also effective in bacterial infections. Epidemiological research shows that IgE level is increased when infected by
39:
Degranulation processes 1: antigen; 2: IgE antibody; 3: FcĪµRI receptor; 4: preformed mediators (histamine, proteases, chemokines, heparin); 5: granules; 6: mast cell; 7: newly formed mediators (prostaglandins, leukotrienes, thromboxanes,
628:
419:). However, this may not be a requirement for symptoms to occur as has been seen in asthmatics with normal IgE levels in their bloodārecent research has shown that IgE production can occur locally in the nasal mucosa.
2268:
Gauvreau GM, Harris JM, Boulet LP, Scheerens H, Fitzgerald JM, Putnam WS, et al. (July 2014). "Targeting membrane-expressed IgE B cell receptor with an antibody to the M1 prime epitope reduces IgE production".
400:, in which the stimulation of a strong cytotoxic response against cells displaying only small amounts of early cancer markers would be beneficial. If this were the case, anti-IgE treatments such as
612:
interaction. It may be possible to design treatments cheaper than monoclonal antibodies (for instance, small molecule drugs) that use a similar approach to inhibit binding of IgE to its receptor.
1702:
Karagiannis SN, Wang Q, East N, Burke F, Riffard S, Bracher MG, et al. (April 2003). "Activity of human monocytes in IgE antibody-dependent surveillance and killing of ovarian tumor cells".
71:. Monomers of IgE consist of two heavy chains (Īµ chain) and two light chains, with the Īµ chain containing four Ig-like constant domains (CĪµ1āCĪµ4). IgE is thought to be an important part of the
1934:
Holm J, Willumsen N, WĆ¼rtzen PA, Christensen LH, Lund K (April 2011). "Facilitated antigen presentation and its inhibition by blocking IgG antibodies depends on IgE repertoire complexity".
632:
1432:
Rihet P, Demeure CE, Bourgois A, Prata A, Dessein AJ (November 1991). "Evidence for an association between human resistance to
Schistosoma mansoni and high anti-larval IgE levels".
477:, and increased vascular permeability, it is presumed, to allow other immune cells to gain access to tissues, but which can lead to a potentially fatal drop in blood pressure as in
2312:
Wan T, Beavil RL, Fabiane SM, Beavil AJ, Sohi MK, Keown M, et al. (July 2002). "The crystal structure of IgE Fc reveals an asymmetrically bent conformation".
1745:
Busse W, Buhl R, Fernandez
Vidaurre C, Blogg M, Zhu J, Eisner MD, Canvin J (April 2012). "Omalizumab and the risk of malignancy: results from a pooled analysis".
2009:
1609:
576:
IgE-secreting plasma cells go through the intermediate steps of IgE-expressing B lymphoblasts and involves the interaction with IgE-expressing memory B cells.
2101:"Novartis announces XolairĀ® approved in EU as first and only licensed therapy for chronic spontaneous urticaria (CSU) patients unresponsive to antihistamines"
1635:
572:. Long-term uses of systemic corticosteroids are known to cause many serious side effects and are advisable to avoid, if alternative therapies are available.
1864:
Elkayam O, Tamir R, Pick AI, Wysenbeek A (January 1995). "Serum IgE concentrations, disease activity, and atopic disorders in systemic lupus erythematosus".
2372:
2005:
364:. Although controversial at the time, new work supports some of Profetās thoughts on the adaptive role of allergies as a defense against noxious toxins.
388:
immune responses, associated with production of IgE antibodies, which may "increase the resistance of mice to challenge with potentially lethal doses".
608:
2125:
2100:
2045:
193:
986:
Gould HJ, Sutton BJ, Beavil AJ, Beavil RL, McCloskey N, Coker HA, et al. (2003). "The biology of IGE and the basis of allergic disease".
272:
to IgE already bound by the FcĪµRI on mast cells causes cross-linking of the bound IgE and the aggregation of the underlying FcĪµRI, leading to
1821:
Permin H, Wiik A (October 1978). "The prevalence of IgE antinuclear antibodies in rheumatoid arthritis and systemic lupus erythematosus".
264:
IgE can upregulate the expression of both types of FcĪµ receptors. FcĪµRI is expressed on mast cells, basophils, and the antigen-presenting
1021:
Winter WE, Hardt NS, Fuhrman S (September 2000). "Immunoglobulin E: importance in parasitic infections and hypersensitivity responses".
775:"Total and functional parasite specific IgE responses in Plasmodium falciparum-infected patients exhibiting different clinical status"
1475:
Pritchard DI, Quinnell RJ, Walsh EA (February 1995). "Immunity in humans to
Necator americanus: IgE, parasite weight and fecundity".
1156:"Physico-chemical properties of human reaginic antibody. IV. Presence of a unique immunoglobulin as a carrier of reaginic activity"
2365:
461:, and certain interleukins. These chemicals cause many of the symptoms we associate with allergy, such as airway constriction in
376:
would happen if the animal encountered a whole nest of bees, or in the event of a snakebite". The major allergen of bee venom (
695:
Watanabe N, Bruschi F, Korenaga M (April 2005). "IgE: a question of protective immunity in
Trichinella spiralis infection".
2813:
2152:"Unique epitopes on C epsilon mX in IgE-B cell receptors are potentially applicable for targeting IgE-committed B cells"
2358:
2020:
1520:"Allergen-specific IgE and IgG4 are markers of resistance and susceptibility in a human intestinal nematode infection"
2076:
552:, which antagonize the inflammatory mediators histamine and leukotrienes, (2) local or systemic (oral or injectable)
2704:
1891:
Conrad DH, Ford JW, Sturgill JL, Gibb DR (September 2007). "CD23: an overlooked regulator of allergic disease".
1655:"Testing the 'toxin hypothesis of allergy': mast cells, IgE, and innate and acquired immune responses to venoms"
2699:
1301:"The CD23a and CD23b proximal promoters display different sensitivities to exogenous stimuli in B lymphocytes"
2642:
2248:
593:
396:
Although it is not yet well understood, IgE may play an important role in the immune system's recognition of
189:
496:, and is theorized to be of pathogenetic importance in SLE and RA by eliciting a hypersensitivity reaction.
485:
2193:"Antibodies specific for a segment of human membrane IgE deplete IgE-producing B cells in humanized mice"
730:
Pfister K, Turner K, Currie A, Hall E, Jarrett EE (November 1983). "IgE production in rat fascioliasis".
544:
Currently, allergic diseases and asthma are usually treated with one or more of the following drugs: (1)
2129:
2104:
2939:
2908:
2877:
2528:
316:; but IL-4 can induce its expression on the surfaces of macrophages, eosinophils, platelets, and some
2350:
2806:
2708:
2466:
114:
937:
Marichal T, Starkl P, Reber LL, Kalesnikoff J, Oettgen HC, Tsai M, et al. (November 2013).
453:, capable of mediating inflammatory reactions, become "primed", ready to release chemicals like
415:
individuals can have up to ten times the normal level of IgE in their blood (as do sufferers of
2981:
2730:
2448:
2384:
773:
Duarte J, Deshpande P, Guiyedi V, MĆ©cheri S, Fesel C, Cazenave PA, et al. (January 2007).
569:
2677:
2533:
2511:
2039:
999:
106:
2240:
1780:
Takhar P, Smurthwaite L, Coker HA, Fear DJ, Banfield GK, Carr VA, et al. (April 2005).
360:
suggested that allergic reactions have evolved as a last line of defense to protect against
2925:
2694:
2627:
2538:
2462:
1561:"IgE antibodies, FcĪµRIĪ±, and IgE-mediated local anaphylaxis can limit snake venom toxicity"
886:
561:
489:
87:
60:
1559:
Starkl P, Marichal T, Gaudenzio N, Reber LL, Sibilano R, Tsai M, Galli SJ (January 2016).
8:
2986:
2799:
2754:
2689:
2672:
2506:
2424:
499:
Regulation of IgE levels through control of B cell differentiation to antibody-secreting
81:
890:
827:
Profet M (March 1991). "The function of allergy: immunological defense against toxins".
367:
In 2013 it emerged that IgE-antibodies play an essential role in acquired resistance to
2574:
2337:
2294:
2217:
2192:
1916:
1846:
1834:
1727:
1679:
1654:
1585:
1560:
1500:
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1376:
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1221:
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1106:
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1057:
963:
938:
907:
874:
852:
801:
774:
755:
743:
677:
556:, which suppress a broad spectrum of inflammatory mechanisms, (3) short or long-acting
441:
pollen, food protein, etc.) has a unique long-lived interaction with its high-affinity
430:
416:
372:
340:
173:
2126:"Novartis announces US FDA approval of XolairĀ® for chronic idiopathic urticaria (CIU)"
2068:
1983:
1353:
2622:
2388:
2329:
2286:
2222:
2173:
2082:
2072:
1987:
1951:
1908:
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1803:
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1492:
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1189:
1177:
1128:
1087:
1038:
1003:
968:
912:
844:
806:
747:
712:
669:
648:"Helminths, allergic disorders and IgE-mediated immune responses: where do we stand?"
474:
134:
130:
126:
93:
35:
2341:
2298:
1920:
1850:
1731:
1504:
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681:
511:
may also allow facilitated antigen presentation, an IgE-dependent mechanism whereby
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2742:
2682:
2654:
2649:
2617:
2604:
2594:
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1979:
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759:
739:
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659:
377:
288:
157:
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2637:
2282:
1782:"Allergen drives class switching to IgE in the nasal mucosa in allergic rhinitis"
1536:
1519:
954:
557:
553:
549:
198:
177:
172:
IgE was simultaneously discovered in 1966 and 1967 by two independent groups: by
141:
reactions to drugs, bee stings, and antigen preparations used in desensitization
72:
1798:
1781:
527:
2 response, one of the hallmarks of which is the production of more antibodies.
2953:
2664:
2609:
2550:
2470:
2443:
2004:
1947:
1758:
1576:
1262:
1073:
939:"A beneficial role for immunoglobulin E in host defense against honeybee venom"
597:
545:
520:
348:
in humans. It is most likely beneficial in removal of hookworms from the lung.
304:
300:
265:
76:
56:
2150:
Chen JB, Wu PC, Hung AF, Chu CY, Tsai TF, Yu HM, et al. (February 2010).
1904:
1670:
2975:
2632:
2521:
2191:
Brightbill HD, Jeet S, Lin Z, Yan D, Zhou M, Tan M, et al. (June 2010).
2168:
2151:
1400:
1172:
1155:
1034:
708:
565:
536:
testing or testing for immunoglobulin G (IgG) can support allergy diagnosis.
357:
296:
292:
284:
273:
142:
1636:"Severe Allergies to Bee Stings may be Malfunctioning Evolutionary Response"
1610:"Bee sting allergy could be a defense response gone haywire, scientists say"
1317:
1300:
291:(SCF), which both help the mast cells survive and accumulate in tissue, and
2599:
2584:
2579:
2516:
2414:
2333:
2290:
2226:
2177:
2086:
1991:
1955:
1912:
1807:
1766:
1723:
1688:
1594:
1545:
1445:
1418:
1361:
1326:
1091:
1042:
1007:
972:
916:
810:
716:
673:
500:
442:
156:
individual are only 0.05% of the Ig concentration, compared to 75% for the
138:
1877:
1715:
1496:
1453:
1271:
1230:
1181:
1132:
848:
791:
751:
664:
647:
1842:
478:
458:
281:
260:(type II FcĪµ receptor), also known as CD23, the low-affinity IgE receptor
220:
161:
149:
68:
898:
276:(the release of mediators) and the secretion of several types of type 2
2722:
2475:
2381:
2061:
AntiāIgE Antibodies for the
Treatment of IgEāMediated Allergic Diseases
601:
585:
450:
401:
240:
232:
2780:
2485:
2380:
2208:
493:
454:
446:
427:
368:
224:
122:
1392:
1246:"Histamine release from human leukocytes by anti-gamma E antibodies"
560:, which relax smooth muscle of constricted airway in asthma, or (4)
484:
IgE is known to be elevated in various autoimmune disorders such as
257:
137:. IgE also plays a pivotal role in responses to allergens, such as:
2948:
2822:
2770:
2555:
2543:
2501:
2455:
2419:
840:
581:
423:
345:
277:
244:
236:
228:
185:
101:
98:
52:
2325:
251:
2775:
2589:
2438:
2409:
512:
438:
434:
269:
204:
117:, which manifests in various allergic diseases, such as allergic
1744:
1243:
2747:
2735:
2480:
2431:
1933:
1205:"Immunological studies of an atypical (myeloma) immunoglobulin"
589:
466:
462:
412:
397:
317:
313:
208:
181:
153:
118:
110:. IgE may have evolved as a defense to protect against venoms.
64:
1968:
1244:
Ishizaka T, Ishizaka K, Johansson SG, Bennich H (April 1969).
936:
2899:
2791:
2267:
1340:
Novak N, Kraft S, Bieber T (December 2001). "IgE receptors".
772:
577:
503:
is thought to involve the "low-affinity" receptor FcĪµRII, or
470:
361:
97:. IgE is also utilized during immune defense against certain
27:
1558:
219:
IgE primes the IgE-mediated allergic response by binding to
180:
at the
Children's Asthma Research Institute and Hospital in
164:, one of the most rapid and severe immunological reactions.
2918:
2913:
2887:
2882:
1517:
568:
of mast cells that is normally triggered by IgE-binding at
516:
508:
504:
308:
1823:
Acta
Pathologica et Microbiologica Scandinavica, Section C
1779:
2063:. Advances in Immunology. Vol. 93. pp. 63ā119.
1863:
1431:
1153:
519:
are able to present allergen to (and stimulate) specific
381:
1701:
307:, which in turn activate group 2-innate lymphoid cells (
1653:
Tsai M, Starkl P, Marichal T, Galli SJ (October 2015).
1652:
985:
872:
729:
694:
351:
160:
at 10 mg/ml. Despite this, it is capable of triggering
2311:
1890:
1474:
19:
2937:
2017:
Choosing Wisely: An
Initiative of the ABIM Foundation
2010:"Five Things Physicians and Patients Should Question"
254:(type I FcĪµ receptor), the high-affinity IgE receptor
31:
The role of mast cells in the development of allergy.
2190:
1627:
1375:
Abraham, Soman N.; St. John, Ashley L. (June 2010).
2006:
American Academy of Allergy, Asthma, and Immunology
1056:Reber, LL; Hernandez, JD; Galli, SJ (August 2017).
1055:
1298:
1154:Ishizaka K, Ishizaka T, Hornbrook MM (July 1966).
1020:
873:Palm NW, Rosenstein RK, Medzhitov R (April 2012).
539:
609:Randall Division of Cell and Molecular Biophysics
247:in humans. There are two types of FcĪµ receptors:
211:. Their joint paper was published in April 1969.
2973:
1601:
1339:
1237:
1202:
1857:
1814:
1374:
1023:Archives of Pathology & Laboratory Medicine
2058:
1962:
1936:The Journal of Allergy and Clinical Immunology
1747:The Journal of Allergy and Clinical Immunology
1565:The Journal of Allergy and Clinical Immunology
1377:"Mast cell-orchestrated immunity to pathogens"
1062:The Journal of Allergy and Clinical Immunology
2807:
2366:
2149:
596:, which cannot be adequately treated with H1-
148:IgE is typically the least abundant isotype:
2261:
2184:
2143:
2052:
2044:: CS1 maint: multiple names: authors list (
1927:
1884:
1738:
1511:
1333:
1292:
1468:
1299:Ewart MA, Ozanne BW, Cushley W (May 2002).
1196:
2814:
2800:
2373:
2359:
1972:Annals of Allergy, Asthma & Immunology
1820:
2216:
2167:
2059:Chang TW, Wu PC, Hsu CL, Hung AF (2007).
1998:
1797:
1678:
1584:
1535:
1408:
1316:
1261:
1220:
1171:
1122:
1104:
1081:
962:
906:
800:
790:
663:
1607:
1203:Johansson SG, Bennich H (October 1967).
1000:10.1146/annurev.immunol.21.120601.141103
129:, food allergies, and specific types of
34:
26:
18:
422:IgE that can specifically recognise an
2974:
2128:. Novartis. 2014-03-21. Archived from
2103:. Novartis. 2014-03-06. Archived from
826:
426:(typically this is a protein, such as
328:
2795:
2354:
2197:The Journal of Clinical Investigation
1633:
766:
1518:Turner JD, et al. (June 2005).
1058:"The pathophysiology of anaphylaxis"
932:
930:
928:
926:
868:
866:
822:
820:
530:
352:Toxin hypothesis of allergic disease
268:in both mice and humans. Binding of
1634:Foley, James A. (25 October 2013).
1608:Sharlach, Molly (24 October 2013).
645:
13:
1893:Current Allergy and Asthma Reports
1835:10.1111/j.1699-0463.1978.tb02587.x
1489:10.1111/j.1365-3024.1995.tb00968.x
1124:10.1111/j.1398-9995.1993.tb00687.x
744:10.1111/j.1365-3024.1983.tb00775.x
604:, is in phase IIb clinical trial.
407:
113:IgE also has an essential role in
14:
2998:
923:
863:
817:
523:, causing the perpetuation of a T
231:. Fc receptors are also found on
23:The structure of the IgE antibody
2959:
2947:
2305:
2233:
2118:
2093:
1773:
1695:
1646:
1552:
1425:
1368:
1147:
1098:
1049:
1014:
829:The Quarterly Review of Biology
540:Drugs targeting the IgE pathway
63:") that has been found only in
16:Immunoglobulin E (IgE) Antibody
2821:
2700:Immunoglobulin class switching
2271:Science Translational Medicine
1704:European Journal of Immunology
1434:European Journal of Immunology
1105:Stanworth DR (February 1993).
979:
723:
688:
652:European Journal of Immunology
639:
621:
1:
2249:National Institutes of Health
2069:10.1016/S0065-2776(06)93002-8
1984:10.1016/S1081-1206(10)60220-7
1659:Current Opinion in Immunology
1614:Stanford Medicine News Center
1354:10.1016/s0952-7915(01)00285-0
1342:Current Opinion in Immunology
615:
594:chronic spontaneous urticaria
75:against infection by certain
2283:10.1126/scitranslmed.3008961
1537:10.1016/j.micinf.2005.03.036
955:10.1016/j.immuni.2013.10.005
607:In 2002, researchers at the
214:
167:
7:
1799:10.4049/jimmunol.174.8.5024
988:Annual Review of Immunology
323:
10:
3003:
2529:Polyclonal B cell response
1948:10.1016/j.jaci.2011.01.062
1759:10.1016/j.jaci.2012.01.033
1577:10.1016/j.jaci.2015.08.005
1263:10.4049/jimmunol.102.4.884
1074:10.1016/j.jaci.2017.06.003
2870:
2829:
2763:
2721:
2663:
2564:
2494:
2402:
2395:
1905:10.1007/s11882-007-0050-y
1671:10.1016/j.coi.2015.07.001
1381:Nature Reviews Immunology
391:
2169:10.4049/jimmunol.0902437
1173:10.4049/jimmunol.97.1.75
1035:10.5858/2000-124-1382-IE
875:"Allergic host defences"
709:10.1016/j.pt.2005.02.010
465:, local inflammation in
223:found on the surface of
67:. IgE is synthesised by
1318:10.1038/sj.gene.6363848
115:type I hypersensitivity
2643:Tolerance in pregnancy
2385:adaptive immune system
1524:Microbes and Infection
1446:10.1002/eji.1830211106
1107:"The discovery of IgE"
697:Trends in Parasitology
41:
32:
24:
2678:Somatic hypermutation
2512:Polyclonal antibodies
2507:Monoclonal antibodies
2156:Journal of Immunology
1786:Journal of Immunology
1716:10.1002/eji.200323185
1250:Journal of Immunology
1160:Journal of Immunology
792:10.1186/1475-2875-6-1
665:10.1002/eji.200737314
635:on September 6, 2008.
562:mast cell stabilizers
107:Plasmodium falciparum
38:
30:
22:
2926:Heavy-chain antibody
2695:Junctional diversity
2463:Antigen presentation
629:"Antibody structure"
564:, which inhibit the
490:rheumatoid arthritis
152:IgE levels in a non-
88:Trichinella spiralis
2690:V(D)J recombination
2673:Affinity maturation
2425:Antigenic variation
2026:on November 3, 2012
1477:Parasite Immunology
899:10.1038/nature11047
891:2012Natur.484..465P
732:Parasite Immunology
646:Erb KJ (May 2007).
336:Schistosoma mansoni
329:Parasite hypothesis
82:Schistosoma mansoni
2245:ClinicalTrials.gov
1571:(1): 246ā257.e11.
1305:Genes and Immunity
417:hyper-IgE syndrome
341:Necator americanus
174:Kimishige Ishizaka
42:
33:
25:
2935:
2934:
2789:
2788:
2717:
2716:
2467:professional APCs
2314:Nature Immunology
1640:Nature World News
531:Role in diagnosis
475:allergic rhinitis
135:atopic dermatitis
131:chronic urticaria
127:allergic rhinitis
94:Fasciola hepatica
2994:
2964:
2963:
2962:
2952:
2951:
2943:
2816:
2809:
2802:
2793:
2792:
2683:Clonal selection
2655:Immune privilege
2650:Immunodeficiency
2605:Cross-reactivity
2595:Hypersensitivity
2400:
2399:
2375:
2368:
2361:
2352:
2351:
2346:
2345:
2309:
2303:
2302:
2277:(243): 243ra85.
2265:
2259:
2258:
2256:
2255:
2237:
2231:
2230:
2220:
2209:10.1172/JCI40141
2188:
2182:
2181:
2171:
2147:
2141:
2140:
2138:
2137:
2122:
2116:
2115:
2113:
2112:
2097:
2091:
2090:
2056:
2050:
2049:
2043:
2035:
2033:
2031:
2025:
2019:. Archived from
2014:
2002:
1996:
1995:
1966:
1960:
1959:
1931:
1925:
1924:
1888:
1882:
1881:
1861:
1855:
1854:
1818:
1812:
1811:
1801:
1777:
1771:
1770:
1742:
1736:
1735:
1699:
1693:
1692:
1682:
1650:
1644:
1643:
1631:
1625:
1624:
1622:
1620:
1605:
1599:
1598:
1588:
1556:
1550:
1549:
1539:
1515:
1509:
1508:
1472:
1466:
1465:
1429:
1423:
1422:
1412:
1372:
1366:
1365:
1337:
1331:
1330:
1320:
1296:
1290:
1289:
1287:
1286:
1265:
1241:
1235:
1234:
1224:
1200:
1194:
1193:
1175:
1151:
1145:
1144:
1126:
1102:
1096:
1095:
1085:
1053:
1047:
1046:
1018:
1012:
1011:
983:
977:
976:
966:
934:
921:
920:
910:
885:(7395): 465ā72.
870:
861:
860:
824:
815:
814:
804:
794:
770:
764:
763:
727:
721:
720:
692:
686:
685:
667:
643:
637:
636:
631:. Archived from
625:
550:antileukotrienes
378:phospholipase A2
289:stem cell factor
202:
190:Gunnar Johansson
121:, most types of
45:Immunoglobulin E
3002:
3001:
2997:
2996:
2995:
2993:
2992:
2991:
2972:
2971:
2970:
2960:
2958:
2946:
2938:
2936:
2931:
2866:
2825:
2820:
2790:
2785:
2759:
2713:
2659:
2638:Clonal deletion
2566:
2560:
2490:
2391:
2379:
2349:
2310:
2306:
2266:
2262:
2253:
2251:
2239:
2238:
2234:
2189:
2185:
2148:
2144:
2135:
2133:
2124:
2123:
2119:
2110:
2108:
2099:
2098:
2094:
2079:
2057:
2053:
2037:
2036:
2029:
2027:
2023:
2012:
2003:
1999:
1967:
1963:
1932:
1928:
1889:
1885:
1862:
1858:
1819:
1815:
1778:
1774:
1753:(4): 983ā9.e6.
1743:
1739:
1700:
1696:
1651:
1647:
1632:
1628:
1618:
1616:
1606:
1602:
1557:
1553:
1516:
1512:
1473:
1469:
1440:(11): 2679ā86.
1430:
1426:
1393:10.1038/nri2782
1373:
1369:
1338:
1334:
1297:
1293:
1284:
1282:
1242:
1238:
1201:
1197:
1152:
1148:
1103:
1099:
1054:
1050:
1019:
1015:
984:
980:
935:
924:
871:
864:
825:
818:
779:Malaria Journal
771:
767:
728:
724:
693:
689:
644:
640:
627:
626:
622:
618:
558:bronchodilators
554:corticosteroids
542:
533:
526:
410:
408:Role in disease
394:
385:
373:Russell's viper
354:
331:
326:
266:dendritic cells
217:
196:
178:Teruko Ishizaka
170:
77:parasitic worms
73:immune response
51:) is a type of
17:
12:
11:
5:
3000:
2990:
2989:
2984:
2969:
2968:
2956:
2933:
2932:
2930:
2929:
2923:
2922:
2921:
2916:
2905:
2904:
2903:
2902:
2892:
2891:
2890:
2885:
2874:
2872:
2868:
2867:
2865:
2864:
2859:
2854:
2849:
2844:
2839:
2833:
2831:
2827:
2826:
2819:
2818:
2811:
2804:
2796:
2787:
2786:
2784:
2783:
2778:
2773:
2767:
2765:
2761:
2760:
2758:
2757:
2752:
2751:
2750:
2740:
2739:
2738:
2727:
2725:
2719:
2718:
2715:
2714:
2712:
2711:
2702:
2697:
2692:
2687:
2686:
2685:
2680:
2669:
2667:
2665:Immunogenetics
2661:
2660:
2658:
2657:
2652:
2647:
2646:
2645:
2640:
2635:
2630:
2625:
2613:
2612:
2610:Co-stimulation
2607:
2602:
2597:
2592:
2587:
2582:
2577:
2570:
2568:
2562:
2561:
2559:
2558:
2553:
2551:Immune complex
2547:
2546:
2541:
2536:
2531:
2526:
2525:
2524:
2519:
2514:
2509:
2498:
2496:
2492:
2491:
2489:
2488:
2483:
2478:
2473:
2471:Dendritic cell
2459:
2458:
2453:
2452:
2451:
2449:Conformational
2446:
2435:
2434:
2429:
2428:
2427:
2422:
2417:
2406:
2404:
2397:
2393:
2392:
2378:
2377:
2370:
2363:
2355:
2348:
2347:
2304:
2260:
2232:
2203:(6): 2218ā29.
2183:
2162:(4): 1748ā56.
2142:
2117:
2092:
2077:
2051:
1997:
1961:
1942:(4): 1029ā37.
1926:
1883:
1856:
1813:
1792:(8): 5024ā32.
1772:
1737:
1710:(4): 1030ā40.
1694:
1645:
1626:
1600:
1551:
1530:(7ā8): 990ā6.
1510:
1467:
1424:
1387:(6): 440ā452.
1367:
1332:
1291:
1236:
1195:
1146:
1097:
1068:(2): 335ā348.
1048:
1013:
978:
922:
862:
841:10.1086/417049
816:
765:
722:
687:
638:
619:
617:
614:
598:antihistamines
584:antibody drug
546:antihistamines
541:
538:
532:
529:
524:
521:T helper cells
445:FcĪµRI so that
409:
406:
393:
390:
383:
353:
350:
330:
327:
325:
322:
262:
261:
255:
216:
213:
169:
166:
57:immunoglobulin
15:
9:
6:
4:
3:
2:
2999:
2988:
2985:
2983:
2982:Glycoproteins
2980:
2979:
2977:
2967:
2957:
2955:
2950:
2945:
2944:
2941:
2927:
2924:
2920:
2917:
2915:
2912:
2911:
2910:
2907:
2906:
2901:
2898:
2897:
2896:
2893:
2889:
2886:
2884:
2881:
2880:
2879:
2876:
2875:
2873:
2869:
2863:
2860:
2858:
2855:
2853:
2850:
2848:
2845:
2843:
2840:
2838:
2835:
2834:
2832:
2828:
2824:
2817:
2812:
2810:
2805:
2803:
2798:
2797:
2794:
2782:
2779:
2777:
2774:
2772:
2769:
2768:
2766:
2762:
2756:
2753:
2749:
2746:
2745:
2744:
2741:
2737:
2734:
2733:
2732:
2729:
2728:
2726:
2724:
2720:
2710:
2706:
2703:
2701:
2698:
2696:
2693:
2691:
2688:
2684:
2681:
2679:
2676:
2675:
2674:
2671:
2670:
2668:
2666:
2662:
2656:
2653:
2651:
2648:
2644:
2641:
2639:
2636:
2634:
2633:Clonal anergy
2631:
2629:
2626:
2624:
2621:
2620:
2619:
2615:
2614:
2611:
2608:
2606:
2603:
2601:
2598:
2596:
2593:
2591:
2588:
2586:
2583:
2581:
2578:
2576:
2572:
2571:
2569:
2563:
2557:
2554:
2552:
2549:
2548:
2545:
2542:
2540:
2537:
2535:
2532:
2530:
2527:
2523:
2522:Microantibody
2520:
2518:
2515:
2513:
2510:
2508:
2505:
2504:
2503:
2500:
2499:
2497:
2493:
2487:
2484:
2482:
2479:
2477:
2474:
2472:
2468:
2464:
2461:
2460:
2457:
2454:
2450:
2447:
2445:
2442:
2441:
2440:
2437:
2436:
2433:
2430:
2426:
2423:
2421:
2418:
2416:
2413:
2412:
2411:
2408:
2407:
2405:
2401:
2398:
2394:
2390:
2386:
2383:
2376:
2371:
2369:
2364:
2362:
2357:
2356:
2353:
2343:
2339:
2335:
2331:
2327:
2326:10.1038/ni811
2323:
2319:
2315:
2308:
2300:
2296:
2292:
2288:
2284:
2280:
2276:
2272:
2264:
2250:
2246:
2242:
2236:
2228:
2224:
2219:
2214:
2210:
2206:
2202:
2198:
2194:
2187:
2179:
2175:
2170:
2165:
2161:
2157:
2153:
2146:
2132:on 2014-12-03
2131:
2127:
2121:
2107:on 2014-12-18
2106:
2102:
2096:
2088:
2084:
2080:
2078:9780123737076
2074:
2070:
2066:
2062:
2055:
2047:
2041:
2022:
2018:
2011:
2007:
2001:
1993:
1989:
1985:
1981:
1978:(6): 580ā92.
1977:
1973:
1965:
1957:
1953:
1949:
1945:
1941:
1937:
1930:
1922:
1918:
1914:
1910:
1906:
1902:
1898:
1894:
1887:
1879:
1875:
1871:
1867:
1860:
1852:
1848:
1844:
1840:
1836:
1832:
1828:
1824:
1817:
1809:
1805:
1800:
1795:
1791:
1787:
1783:
1776:
1768:
1764:
1760:
1756:
1752:
1748:
1741:
1733:
1729:
1725:
1721:
1717:
1713:
1709:
1705:
1698:
1690:
1686:
1681:
1676:
1672:
1668:
1664:
1660:
1656:
1649:
1641:
1637:
1630:
1615:
1611:
1604:
1596:
1592:
1587:
1582:
1578:
1574:
1570:
1566:
1562:
1555:
1547:
1543:
1538:
1533:
1529:
1525:
1521:
1514:
1506:
1502:
1498:
1494:
1490:
1486:
1482:
1478:
1471:
1463:
1459:
1455:
1451:
1447:
1443:
1439:
1435:
1428:
1420:
1416:
1411:
1406:
1402:
1398:
1394:
1390:
1386:
1382:
1378:
1371:
1363:
1359:
1355:
1351:
1347:
1343:
1336:
1328:
1324:
1319:
1314:
1311:(3): 158ā64.
1310:
1306:
1302:
1295:
1281:
1277:
1273:
1269:
1264:
1259:
1256:(4): 884ā92.
1255:
1251:
1247:
1240:
1232:
1228:
1223:
1218:
1215:(4): 381ā94.
1214:
1210:
1206:
1199:
1191:
1187:
1183:
1179:
1174:
1169:
1165:
1161:
1157:
1150:
1142:
1138:
1134:
1130:
1125:
1120:
1116:
1112:
1108:
1101:
1093:
1089:
1084:
1079:
1075:
1071:
1067:
1063:
1059:
1052:
1044:
1040:
1036:
1032:
1029:(9): 1382ā5.
1028:
1024:
1017:
1009:
1005:
1001:
997:
993:
989:
982:
974:
970:
965:
960:
956:
952:
949:(5): 963ā75.
948:
944:
940:
933:
931:
929:
927:
918:
914:
909:
904:
900:
896:
892:
888:
884:
880:
876:
869:
867:
858:
854:
850:
846:
842:
838:
834:
830:
823:
821:
812:
808:
803:
798:
793:
788:
784:
780:
776:
769:
761:
757:
753:
749:
745:
741:
738:(6): 587ā93.
737:
733:
726:
718:
714:
710:
706:
702:
698:
691:
683:
679:
675:
671:
666:
661:
658:(5): 1170ā3.
657:
653:
649:
642:
634:
630:
624:
620:
613:
610:
605:
603:
599:
595:
591:
587:
583:
579:
573:
571:
567:
566:degranulation
563:
559:
555:
551:
547:
537:
528:
522:
518:
514:
510:
506:
502:
497:
495:
491:
487:
482:
480:
476:
473:secretion in
472:
468:
464:
460:
456:
452:
448:
444:
440:
436:
432:
429:
425:
420:
418:
414:
405:
403:
399:
389:
387:
379:
374:
370:
365:
363:
359:
358:Margie Profet
349:
347:
343:
342:
337:
321:
319:
315:
310:
306:
302:
298:
294:
290:
286:
283:
279:
275:
274:degranulation
271:
267:
259:
256:
253:
250:
249:
248:
246:
242:
238:
234:
230:
226:
222:
212:
210:
206:
200:
195:
191:
187:
183:
179:
176:and his wife
175:
165:
163:
159:
155:
151:
146:
144:
143:immunotherapy
140:
136:
132:
128:
124:
120:
116:
111:
109:
108:
103:
100:
96:
95:
90:
89:
84:
83:
78:
74:
70:
66:
62:
58:
54:
50:
46:
37:
29:
21:
2894:
2846:
2600:Inflammation
2585:Alloimmunity
2580:Autoimmunity
2565:Immunity vs.
2517:Autoantibody
2415:Superantigen
2320:(7): 681ā6.
2317:
2313:
2307:
2274:
2270:
2263:
2252:. Retrieved
2244:
2235:
2200:
2196:
2186:
2159:
2155:
2145:
2134:. Retrieved
2130:the original
2120:
2109:. Retrieved
2105:the original
2095:
2060:
2054:
2040:cite journal
2028:. Retrieved
2021:the original
2016:
2000:
1975:
1971:
1964:
1939:
1935:
1929:
1899:(5): 331ā7.
1896:
1892:
1886:
1869:
1865:
1859:
1829:(5): 245ā9.
1826:
1822:
1816:
1789:
1785:
1775:
1750:
1746:
1740:
1707:
1703:
1697:
1662:
1658:
1648:
1639:
1629:
1617:. Retrieved
1613:
1603:
1568:
1564:
1554:
1527:
1523:
1513:
1480:
1476:
1470:
1437:
1433:
1427:
1384:
1380:
1370:
1348:(6): 721ā6.
1345:
1341:
1335:
1308:
1304:
1294:
1283:. Retrieved
1253:
1249:
1239:
1212:
1208:
1198:
1166:(1): 75ā85.
1163:
1159:
1149:
1117:(2): 67ā71.
1114:
1110:
1100:
1065:
1061:
1051:
1026:
1022:
1016:
991:
987:
981:
946:
942:
882:
878:
835:(1): 23ā62.
832:
828:
782:
778:
768:
735:
731:
725:
703:(4): 175ā8.
700:
696:
690:
655:
651:
641:
633:the original
623:
606:
588:(trade name
574:
543:
534:
501:plasma cells
498:
483:
469:, increased
459:leukotrienes
421:
411:
395:
380:) induces a
366:
355:
339:
335:
332:
263:
221:Fc receptors
218:
194:Hans Bennich
171:
147:
139:anaphylactic
112:
105:
92:
86:
80:
79:, including
69:plasma cells
48:
44:
43:
2909:Heavy chain
2878:Light chain
2723:Lymphocytes
2382:Lymphocytic
2241:"MEMP1972A"
1872:(1): 94ā6.
1619:20 November
1483:(2): 71ā5.
994:: 579ā628.
515:expressing
479:anaphylaxis
437:, grass or
282:interleukin
241:macrophages
233:eosinophils
197: [
162:anaphylaxis
150:blood serum
2987:Antibodies
2976:Categories
2830:Main types
2823:Antibodies
2764:Substances
2628:Peripheral
2616:Inaction:
2495:Antibodies
2476:Macrophage
2389:complement
2254:2014-12-04
2136:2014-12-04
2111:2014-12-04
2030:August 14,
1285:2016-02-29
1209:Immunology
616:References
602:quilizumab
586:omalizumab
492:(RA), and
451:mast cells
402:omalizumab
225:mast cells
2895:surrogate
2781:Cytolysin
2771:Cytokines
2618:Tolerance
2567:tolerance
2486:Immunogen
1401:1474-1741
1280:255338552
1190:255620017
494:psoriasis
455:histamine
447:basophils
428:dust mite
369:honey bee
346:nematodes
278:cytokines
245:platelets
237:monocytes
229:basophils
215:Receptors
188:, and by
168:Discovery
123:sinusitis
102:parasites
99:protozoan
2966:Medicine
2731:Cellular
2575:Immunity
2573:Action:
2556:Paratope
2544:Idiotype
2534:Allotype
2502:Antibody
2456:Mimotope
2420:Allergen
2403:Antigens
2396:Lymphoid
2342:32347451
2334:12068291
2299:41593528
2291:24990880
2227:20458139
2178:20083663
2087:17383539
1992:19119701
1956:21377718
1921:24816595
1913:17697638
1851:13737751
1808:15814733
1767:22365654
1732:29495137
1724:12672069
1689:26210895
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1595:26410782
1546:15961339
1505:41222700
1419:20498670
1362:11677096
1327:12070780
1141:36262710
1092:28780941
1043:10975945
1008:12500981
973:24210352
943:Immunity
917:22538607
811:17204149
717:15780839
682:24519249
674:17447233
582:anti-IgE
443:receptor
424:allergen
356:In 1981
324:Function
270:antigens
186:Colorado
104:such as
53:antibody
2954:Biology
2940:Portals
2776:Opsonin
2755:NK cell
2743:Humoral
2623:Central
2590:Allergy
2539:Isotype
2439:Epitope
2410:Antigen
2247:. U.S.
2218:2877936
1878:7741196
1866:Allergy
1680:4593748
1586:4715494
1497:7761110
1462:1103861
1454:1936116
1410:4469150
1272:4181251
1231:4168094
1222:1409218
1182:4162440
1133:8457034
1111:Allergy
1083:5657389
964:4164235
908:3596087
887:Bibcode
857:5648170
849:2052671
802:1781948
760:1530964
752:6657297
513:B cells
439:ragweed
435:Fel d 1
431:Der p 1
318:T cells
314:B cells
205:Uppsala
65:mammals
61:isotype
2928:/IgNAR
2871:Chains
2748:B cell
2736:T cell
2481:B cell
2444:Linear
2432:Hapten
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2332:
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467:eczema
463:asthma
433:, cat
413:Atopic
398:cancer
392:Cancer
362:venoms
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303:, and
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182:Denver
154:atopic
119:asthma
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1909:PMID
1874:PMID
1839:PMID
1804:PMID
1763:PMID
1720:PMID
1685:PMID
1621:2019
1591:PMID
1542:PMID
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227:and
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2862:IgY
2857:IgM
2852:IgG
2847:IgE
2842:IgD
2837:IgA
2709:HLA
2705:MHC
2322:doi
2279:doi
2213:PMC
2205:doi
2201:120
2164:doi
2160:184
2065:doi
1980:doi
1976:101
1944:doi
1940:127
1901:doi
1831:doi
1827:86C
1794:doi
1790:174
1755:doi
1751:129
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1675:PMC
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1581:PMC
1573:doi
1569:137
1532:doi
1485:doi
1442:doi
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1350:doi
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1258:doi
1254:102
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