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Testing of IgG and IgG4 to foods is not recommended / Position of the German Society of Allergy and Clinical Immunology (DGAKI) a , the Physician's Society of German Allergists (ÄDA) and the Society of Pediatric Allergy and Environmental Medicine (GPA), the Austrian Society of Allergy and Immunology (ÖGAI) and the Swiss Society of Allergy and Immunology (SGAI) after Adoption of the Task Force Report b of the European Academy of Allergy and Clinical Immunology (EAACI)

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J Lab Med 2010;34(4) 2010 by Walter de Gruyter Berlin New York. DOI 10.1515/JLM.2010.033et
Article in press - uncorrected proof
Allergy and Autoimmunity Redaktion: H. Renz
Testing of IgG and IgG
to foods is not recommended
Position of the German Society of Allergy and Clinical Immunology
, the Physician’s Society of German Allergists (A
¨DA) and the
Society of Pediatric Allergy and Environmental Medicine (GPA), the
Austrian Society of Allergy and Immunology (O
¨GAI) and the Swiss
Society of Allergy and Immunology (SGAI) after Adoption of the Task
Force Report
of the European Academy of Allergy and Clinical
Immunology (EAACI)
Jo¨rg Kleine-Tebbe
*, Imke Reese
, Barbara K.
, Kirsten Beyer
, Stephan Erdmann
Thomas Fuchs
, Margot Henzgen
, Annice
, Isidor Huttegger
, Lothar Ja¨ger
, Uta
, Ute Lepp
, Bodo Niggemann
, Martin
, Joachim Saloga
, Zsolt Sze´pfalusi
Torsten Zuberbier
, Thomas Werfel
, Stefan Vieths
and Margitta Worm
Allergie- und Asthma-Zentrum Westend, Berlin, Germany
Erna¨hrungsberatung, Mu¨ nchen, Germany
Dermatologische Klinik, Universita¨tsSpital Zu¨ rich, Zu¨rich,
Klinik fu¨r Pa¨diatrie m. S. Pneumologie und Immunologie,
Charite´-Universita¨ tsmedizin Berlin, Germany
Praxis fu¨ r Dermatologie, Bergisch-Gladbach, Germany
Abteilung Dermatologie und Venerologie,
Universita¨tsmedizin Go¨ ttingen, Go¨ttingen, Germany
Pneumologie und Allergologie, Klinik fu¨ r Innere Medizin
I, Friedrich-Schiller-Universita¨t, Jena, Germany
Klinik und Poliklinik fu¨ r Dermatologie und Venerologie,
Medizinische Hochschule Hannover, Hannover, Germany
Universita¨tsklinik fu¨r Kinder- und Jugendheilkunde,
Paracelsus Medizinische Privatuniversita¨t, Salzburger
Landeskliniken, Salzburg, O
Jena, Germany
Abteilung Allergologie, Paul-Ehrlich-Institut, Langen,
Langen, Germany
Herz-Lungen-Praxis Stade, Stade, Germany
Translated and commented by the authors of the DGAKI Food
Allergy Working Group. The original German online version is
available at:
Coordinated by the EAACI Interest Group Allergy Diagnosis and
the EAACI Interest Group Food Allergy.
*Correspondence: Priv.-Doz. Dr. Jo¨ rg Kleine-Tebbe, Allergie-
und Asthma-Zentrum Westend, Spandauer Damm 130, Haus 9,
14050 Berlin, Germany
Tel.: q030/30202910
Fax: q030/30202920
Pa¨diatrische Allergologie und Pneumologie, Hedwig-von-
Rittberg-Zentrum, DRK-Kliniken Westend, Berlin,
Gastroenterologie, Pneumologie und Endokrinologie,
Medizinische Klinik 1, Universita¨t Erlangen, Erlangen,
Universita¨tshautklinik, Johannes-Gutenberg-Universita¨t,
Mainz, Mainz, Germany
Universita¨tsklinik fu¨r Kinder- und Jugendheilkunde,
Medizinische Universita¨t Wien, Vienna, Austria
Allergie-Centrum-Charite´, Klinik fu¨ r Dermatologie,
Venerologie und Allergologie, Charite´ -Universita¨tsmedizin
Berlin, Berlin, Germany
The position of the European Academy of Allergy and Clin-
ical Immunology (EAACI) on immunoglobulin G (IgG) test-
ing to foods w1xhas been well received and its entire content
has been adopted as a translated version by the German,
Austrian and Swiss Allergy Societies.
Due to current scientific understanding IgG(4) antibodies
to foods should not be misinterpreted as an indicator for
disease causing mechanisms but rather as a sign of a normal
(physiological) human immune response after repeated expo-
sure to food components. Therefore, the allergen specific
measurement of IgG or IgG4 antibodies to foods is useless
and is definitely not recommended for the work-up and diag-
nosis of various types of food hypersensitivity w2–5x.
This is also true for chronic diseases and health com-
plaints, falsely believed to be caused by an underlying food
hypersensitivity, which has not yet been diagnosed. These
health problems include chronic inflammatory bowel dis-
eases like irritable bowel disease, Crohn’s disease, colitis
ulcerosa, inflammatory skin diseases like acne, atopic ecze-
ma, psoriasis and general symptoms like migraine, chronic
2Kleine-Tebbe et al.: Preambel IgG-testing
Article in press - uncorrected proof
fatigue, obesity and numerous others. The commonly used
argument for IgG measurements often falsely exchanges
cause and effect. More specifically, elevated physiological
IgG concentrations to foods are often blamed as a cause for
inflammatory responses, instead of being interpreted as a
consequence of such pathology.
For none of these above-mentioned diseases and health
complaints has scientific evidence based on valid, controlled
studies been established, indicating that the presence of
serum IgG or IgG4 antibodies to foods might have a diag-
nostic value or could represent a pathological finding. Meas-
urements of IgG antibodies to foods are therefore not
recommended. This conclusion is not necessarily based on
technical assay flaws, but rather on rejecting the misleading
interpretations of such test results, which are often abused as
a reasoning to recommend unjustified and frequently drastic
diets. These diets will increase the pressure of suffering,
decrease the quality of life, promote uncertainty and even
place these subjects at further health risks.
At present there is no indication for IgG or IgG4 antibody
tests to food items. This type of diagnostic procedure is
strictly not recommened due to a lack of evidence from prop-
erly controlled studies. The authors speaking for the German-
language allergy societies, therefore adopt the European
position in its present form as outlined above.
1. Stapel SO, Asero R, Ballmer-Weber BK, Knol EF, Strobel S,
Vieths S, et al., EAACI Task Force. Testing for IgG
foods is not recommended as a diagnostic tool: EAACI Task
Force Report. Allergy 2008;63:793–6.
2. Kleine-Tebbe J, Ballmer-Weber BK, Beyer K, Erdmann S, Fuchs
T, Henzgen M, et al. In-vitro-Diagnostik und molekulare Grund-
lagen von IgE-vermittelten Nahrungsmittelallergien. Leitlinie
von DGAKI, A
¨GAI und SGAI. Allergo J 2009;
3. Kleine-Tebbe J, Fuchs T, Lepp U, Niggemann B, Saloga J, Vieluf
I, et al. In-vitro-Diagnostik von Nahrungsmittel-Allergien. Aller-
go J 2001;10:333–9.
4. Renz H, Becker W-M, Bufe A, Kleine-Tebbe J, Raulf-Heimsoth
M, Saloga J, et al. In-vitro-Allergiediagnostik. Positionspapier
der Deutschen Gesellschaft fu¨r Allergologie und klinische Immu-
nologie (DGAKI). Arbeitsgruppe ,,In-vitro-Allergiediagnostik‘‘
der Sektion Immunologie. Allergo J 2002;11:492–506.
5. Renz H, Biedermann T, Bufe A, Eberlein B, Jappe U, Ollert M,
et al. In-vitro-Allergiediagnostik. Leitlinie der Deutschen
Gesellschaft fu¨ r Allergologie und klinische Immunologie (DGA-
KI) unter Beteiligung des A
¨rzteverbandes Deutscher Allergolo-
gen (A
¨DA), der Gesellschaft fu¨r Pa¨diatrische Allerlogie und
Umweltmedizin (GPA) und der Deutschen Dermatologische
Gesellschaft (DDG). Allergo J 2010;19:110–28. (www.
ResearchGate has not been able to resolve any citations for this publication.
Full-text available
Entwicklungsstufe: S1 Stand: August 2009 Leitlinien der Gesellschaft für Pädiatrische Allergologie und Umweltmedizin e.V. 1. Zielsetzung Ziel des Positionspapiers ist die wis-senschaftlich begründete Bewertung der verfügbaren Testsysteme der In-vi-tro-Allergiediagnostik. Dazu werden die zur Verfügung stehenden serologischen und zellulären Systeme in Bezug auf Dia-gnostik, Prävention und Therapiekontrol-le evaluiert. Ein weiteres Ziel des Positionspapiers ist, Perspektiven zur Weiterentwicklung der In-vitro-Allergiediagnostik darzustel-len, um im Bereich der Basisdiagnostik und auch spezialisierter Anwendungen die diagnostische Wertigkeit zu steigern. Dies umfasst auch Aspekte zur Weiterent-wicklung der Standardisierung verschie-dener Testverfahren.
Measurement of allergen-specific IgE represents the most useful diagnostic in-vitro test in food allergy, usually being performed after case history and skin test. Hundreds of single allergens and combinations are offered by a number of manufacturers. Different allergens, detection and calibration methods lead to a lack of comparibility of test results, which can also differ substantially from case history, skin test and food challenge results. Cellular laboratory tests should be used for food allergy testing only in individual cases or scientific studies. Food allergens: Food proteins of higher stability (predominantly relevant in early infancy) do rarely cause problems in terms of IgE-testing. At present, use of defined proteins for routine diagnosis of allergen-specific IgE has no advantage compared to whole food allergens. Resulting from sensitizations to pollen allergens or natural rubber latex, IgE will be found to cross reactive, mostly labile allergens from various fruit, vegetable or plant species, being clinically relevant only in case of corresponding symptoms. This supports the recommendation of selected in-vitro testing, focussing on suspected foods. Indication for IgE-testing: Reasonable probability of food allergy, but no clear-cut evidence after case history and skin test; sensitization to foods not suitable for skin testing; severe reactions to foods; skin test or its interpretation not possible. Interpretation of in-vitro results: False positive or negative results due to inappropriate reagents or laboratory errors; clinically irrelevant results by strongly elevated total serum IgE, low cut-off levels or cross reactive allergens. Not suitable for diagnosis of food allergy: Allergen-specific IgG, cytotoxic food test, electro-acupuncture, bioresonance. Unsolved problems: Optimized quality of reagents; calibration and comparability of results from different methods; serological cross reactivity. Future studies adressing clinical relevance of in-vitro results will help to improve diagnosis and interpretation of food allergy.
Wichtigstes Instrument zur In-vitro-Diagnostik von Nahrungsmittelallergien ist die spezifische IgE-Bestimmung, deren Varianten (einzelne Allergenquellen oder -mischungen, Paneltests, Einzelallergene) sich erheblich in ihrer diagnostischen Wertigkeit unterscheiden. Hohe IgE-Werte gegen Hühnerei, Kuhmilch, Erdnuss oder Fisch sind mit erhöhtem Risiko für klinische Reaktionen assoziiert, erlauben aber selten den Verzicht auf eine orale Provokation. Zelluläre Methoden mit basophilen Leukozyten zum indirekten Nachweis IgE-vermittelter Sensibilisierungen gegen Nahrungsmittel sind nur in Einzelfällen sinnvoll. Bestimmte Molekülfamilien (z. B. Bet-v-1-Homologe, Lipidtransferproteine und Profiline) enthalten Allergene ähnlicher Sequenz und Struktur, deren gemeinsame IgE-Bindungsstellen die Grundlage der Kreuzreaktionen darstellen. Kreuzreaktive Kohlenhydratepitope (CCD), häufig pflanzlichen Ursprungs, können ebenfalls IgE binden, das selten klinisch relevant ist. Allergenquellen pflanzlicher (z. B. Nüsse, Früchte, Gemüse) und tierischer Herkunft (Kuhmilch, Hühnerei, Fisch) werden als Extrakte zur Diagnostik eingesetzt, sofern es ihre Qualität erlaubt. Die IgE-Diagnostik mit Einzelallergenen gestattet eine molekülspezifische Diagnostik, deren Bedeutung je nach Allergenquelle und klinischer Charakterisierung der Einzelallergene variiert. Indikationen zur IgE-Diagnostik bestehen bei begründetem Verdacht einer Nahrungsmittelallergie und fehlender Aussage nach Anamnese und Hauttest, bei Sensibilisierung auf hauttestungeeignete Nahrungsmittel, bei bedrohlicher Reaktion auf Nahrungs- mittel, bei Bedingungen, die Hauttests bzw. deren Auswertung nicht zulassen, und im Kindesalter. Die Interpretation hat potenziell falsche Resultate durch unzureichende Reagenzienqualität oder Laborfehler und klinisch irrelevante Ergebnisse durch stark erhöhtes Gesamt-IgE, zu hohe Nachweisempfindlichkeit oder kreuzreagierende Allergene (Interpretationsfehler) zu berücksichtigen. Positive Testergebnisse entsprechen allergenspezifischen Sensibilisierungen, die nur bei korrespondierenden Symptomen relevant sind. Untauglich zur Diagnostik von Nahrungsmittelallergien sind Bioresonanz, Kinesiologie, Elektroakupunktur, zytotoxischer Lebensmitteltest (Methoden ohne Aussagekraft und/oder Überprüfung), Lymphozytentransformationstest, nahrungsmittelspezifisches IgG und IgG4 (Methoden mit unzulässiger Interpretation).
Serological tests for immunoglobulin G4 (IgG4) against foods are persistently promoted for the diagnosis of food-induced hypersensitivity. Since many patients believe that their symptoms are related to food ingestion without diagnostic confirmation of a causal relationship, tests for food-specific IgG4 represent a growing market. Testing for blood IgG4 against different foods is performed with large-scale screening for hundreds of food items by enzyme-linked immunosorbent assay-type and radioallergosorbent-type assays in young children, adolescents and adults. However, many serum samples show positive IgG4 results without corresponding clinical symptoms. These findings, combined with the lack of convincing evidence for histamine-releasing properties of IgG4 in humans, and lack of any controlled studies on the diagnostic value of IgG4 testing in food allergy, do not provide any basis for the hypothesis that food-specific IgG4 should be attributed with an effector role in food hypersensitivity. In contrast to the disputed beliefs, IgG4 against foods indicates that the organism has been repeatedly exposed to food components, recognized as foreign proteins by the immune system. Its presence should not be considered as a factor which induces hypersensitivity, but rather as an indicator for immunological tolerance, linked to the activity of regulatory T cells. In conclusion, food-specific IgG4 does not indicate (imminent) food allergy or intolerance, but rather a physiological response of the immune system after exposition to food components. Therefore, testing of IgG4 to foods is considered as irrelevant for the laboratory work-up of food allergy or intolerance and should not be performed in case of food-related complaints.
  • J Kleine-Tebbe
  • T Fuchs
  • U Lepp
  • B Niggemann
  • J Saloga
  • I Vieluf
Kleine-Tebbe J, Fuchs T, Lepp U, Niggemann B, Saloga J, Vieluf I, et al. In-vitro-Diagnostik von Nahrungsmittel-Allergien. Allergo J 2001;10:333-9.