Dermal Mast Cell Activation by Autoantibodies Against the High Affinity IgE Receptor in Chronic Urticaria

Niimi, Naomasa; Francis, David M.; Kermani, F; O'Donnell, B; Hide, Michihiro; Kobza-Black, A.; Winkelmann, R. K.; Greaves, Malcolm W.; Barr, Robert M.

doi:10.1111/1523-1747.ep12338544

Cited by 290 publications

(260 citation statements)

References 15 publications

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“…However the autoantibodies were only detected in some, but not all of the patients with the positive skin tests. This might indicate that IgE stimulates their mast cells, although further examination would be needed (41,42).…”

Section: Discussionmentioning

confidence: 99%

Monomeric IgE Stimulates NFAT Translocation Into the Nucleus, a Rise in Cytosol Ca2+, Degranulation, and Membrane Ruffling in the Cultured Rat Basophilic Leukemia-2H3 Mast Cell Line

Pandey

Mihara

Fensome-Green

et al. 2004

The Journal of Immunology

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Mast cells are key regulators in allergy and inflammation, and release histamine, cytokines, and other proinflammatory mediators. In the classical view, IgE acts merely to prime mast cells, attaching to FcεRs but not evoking any cell signaling response until cross-linked by the presence of a multivalent allergen. However, several recent studies have reported that IgE alone can promote cell survival and cytokine production in the absence of cross-linking by allergen. In this study we demonstrate that acute addition of monomeric IgE elicits a wide spectrum of responses in the rat basophilic leukemia-2H3 mast cell line, including activation of phospholipases Cγ and D, a rise in cytosol Ca2+, NFAT translocation, degranulation, and membrane ruffling within minutes. Calcium transients persist for hours as long as IgE is present resulting in the maintained translocation of the transcription factor NFAT to the nucleus. Removal of IgE reverses the signaling processes. Our results indicate that, far from simply preparing the cells for a response to allergen, monomeric IgE can stimulate signaling pathways that lead to degranulation, membrane ruffling, and NFAT translocation. The mechanism of activation is likely to be via aggregation of the FcεR1 because activation by IgE can be inhibited with monovalent hapten.

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Section: Discussionmentioning

confidence: 99%

Monomeric IgE Stimulates NFAT Translocation Into the Nucleus, a Rise in Cytosol Ca2+, Degranulation, and Membrane Ruffling in the Cultured Rat Basophilic Leukemia-2H3 Mast Cell Line

Pandey

Mihara

Fensome-Green

et al. 2004

The Journal of Immunology

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“…This work was initiated, as in our case, by careful clinical observation, namely the reactivity of chronic urticaria patients to their own serum after its local injection into their skin, resulting in a typical wheal and flare reaction (19). The same group of investigators showed thereafter that 141 about 30% of their patients with chronic urticaria exhibited these reactions and contained IgG antibodies causing in vitro histamine release from skin slices (20)(21)(22). About 80% of these antibodies were found to be directed against the a chain of the high affinity IgE membrane receptor (FceRIa) and the remainder against IgE (22,23).…”

Section: Autoimmune Mechanisms As a Cause Of Chronic Urticariamentioning

confidence: 92%

“…The same group of investigators showed thereafter that 141 about 30% of their patients with chronic urticaria exhibited these reactions and contained IgG antibodies causing in vitro histamine release from skin slices (20)(21)(22). About 80% of these antibodies were found to be directed against the a chain of the high affinity IgE membrane receptor (FceRIa) and the remainder against IgE (22,23). Roughly 31% of chronic urticaria patient sera apparently contain additional histamine releasing activity of unknown nature (21).…”

Section: Autoimmune Mechanisms As a Cause Of Chronic Urticariamentioning

confidence: 99%

Most chronic urticaria is food‐dependent, and not idiopathic

Henz

Zuberbier

1998

Experimental Dermatology

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Although chronic urticaria is generally thought to be mostly idiopathic, we have recently provided convincing evidence that in the majority of patients, food ingredients provoke the symptoms and sustain the disease. On a diet largely avoiding preservatives, dyes and natural pseudoallergens, 73% of patients experienced remission of more than 6 months duration, starting within the first 3 weeks after initiation of the diet. This response rate is clearly higher than the reported 24% spontaneous remission rate over the same time period. The specificity of the dietary effect was proven 1) by double-blind provocation with pureed pseudoallergen-low versus -rich food and 2) by induction of a clinical response to a 3-week diet low in pseudoallergens, but not to a standard diabetes diet in 3 patients studied in a double-blind crossover design. On double-blind, placebo controlled oral provocation, only 18% of diet-responsive patients reacted to known food preservatives and dyes, but 71% to pureed tomatoes and 44% to their steem extracts. These findings identify naturally occurring pseudoallergens in food as major elicitors of chronic urticaria. In contrast, autoantibodies against FceRIa have been Key words: chronic urticaria -pseudoallergensidentified in only about 30% of chronic urticaria patients, and evidence for diet -aromas -mast cells -FceRIaautoantibodies their truly causative role is still lacking since therapeutic measures work in patients irrespective of the presence or absence of the autoantibodies.

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“…Bu çalışma sonucunda ayrıca OSDT pozitifliği olan hastaların Konstantinou ve arkadaşlarının 25 belirttiği gibi tiroid patolojileri açısından araştırılması gerektiği ifade edilmiştir 22 . Son yayınlarda KÜ tanılı olguların %23-40 kadarında yüksek afiniteli IgE reseptörüne karşı IgG yapısında otoantikorlar saptanmış 26,27 olup, ilave olarak %5-9 kadarında da fonksiyonel anti IgE antikorları saptanmıştır 27,28 . Bu durum kronik otoimmun ürtiker (KOÜ) olarak ifade edilmektedir.…”

Section: Discussionunclassified

Kronik ürtikerli olgularımızın etyolojik değerlendirmesi

Ayyıldız¹,

Sözmen²,

Fırıncı³

et al. 2014

TURKDERM

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ÖzetAmaç: Çocukluk çağında sınırlı veri nedeniyle kronik ürtiker (KÜ) etyolojisi tam olarak anlaşılamamıştır. Bu çalışmada kronik ürtiker tanılı çocuklarda muhtemel etyolojik nedenlerin değerlendirilmesini amaçladık. Gereç ve Yöntem: Ocak 2011 ile Temmuz 2012 tarihleri arasında KÜ tanısı ile kliniğimizde izlenen 18 yaş altı 67 hasta retrospektif olarak analiz edildi. Kronik ürtiker tanılı hastalarda otoimmun hastalıklar, maliniteler, infeksiyonlar gibi etyolojik faktörler araştırıldı. Veriler ortalama±standart sapma (SD) ve yüzde (%) olarak belirtildi. İki grup karşılaştırması Mann-Whitney U metodu kullanılarak yapıldı. P<0,05 olması istatiksel açıdan anlamlı kabul edildi. Bulgular: Kronik ürtiker (KÜ) tanısı olan 67 hasta çalışmaya alındı. Erkek/kız oranı:22/45, ortalama semptom başlangıç yaşı 10,2±4,6 (1-17) yıl idi. Hastaların %7'sinde ANA titresi >1/100 saptanmış olup bu hastaların hiçbirinde romatolojik hastalığa ait klinik özellik belirtilmediği öğrenildi. Hastaların %13,7'sinde tiroid otoantikor pozitifliği olup, hepsine tiroidit tanısı konulduğu ve L-Tiroxin tedavisi başlandığı görüldü. Otolog serum deri testi hastaların %48,2 (n=28)'sinde pozitif olarak saptandı. Sonuç: Çocuklarda infeksiyonlar ve besinler önemli birer KÜ nedeni gibi görünmemektedir. Erişkinlerde olduğu gibi çocuklarda da KÜ etyolojisinde otoreaktif süreçler önemli bir yer tutmaktadır. Bu sonuçlar daha önce KÜ tanılı Türk çocuklarda yapılan çalışmalar ile benzer özelliktedir. (Türk derm 2014; 48: 13-6) Anah tar Ke li me ler: Kronik ürtiker, otolog serum testi, antinükleer antikor, tiroidit Sum maryBackground and Design: The etiology of chronic urticaria (CU) in childhood remains incompletely understood because of limited data. In this study, we aimed to examine possible etiologies of CU in children. Materials and Methods:We retrospectively analyzed the medical records of 67 children who attended our clinic and were diagnosed with CU between January 2001 and July 2012. We investigated the etiological factors contributing to chronic urticaria, such as autoimmune disorders, malignancies and infections. Data were presented as mean±standard deviation (SD) and percentage (%). The comparisons between two groups were conducted using the Mann-Whitney U test. A p value of less than 0.05 was considered statistically significant. Results: Sixty-seven children who met the criteria for CU were included in the study. Male/female ratio was 0.5 and the mean age at onset of symptoms was 10.2±4.6 (range: 1-17) years. In 7% of patients, ANA titers were over 1/100. None of the patients had clinical features of a rheumatic disease, 13.7% of the subjects were positive for thyroid autoantibody. All of them were diagnosed with thyroiditis and received L-thyroxine treatment. Autologous serum skin test was positive in 42.8% of the patients (n=28). Conclusion: In children, infections and foods did not appear to be important causative factors for CU. As in adults, the etiology of CU in children is mainly related to autoreactive processes. This result is similar to ...

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Dermal Mast Cell Activation by Autoantibodies Against the High Affinity IgE Receptor in Chronic Urticaria

Cited by 290 publications

References 15 publications

Monomeric IgE Stimulates NFAT Translocation Into the Nucleus, a Rise in Cytosol Ca2+, Degranulation, and Membrane Ruffling in the Cultured Rat Basophilic Leukemia-2H3 Mast Cell Line

Monomeric IgE Stimulates NFAT Translocation Into the Nucleus, a Rise in Cytosol Ca2+, Degranulation, and Membrane Ruffling in the Cultured Rat Basophilic Leukemia-2H3 Mast Cell Line

Most chronic urticaria is food‐dependent, and not idiopathic

Kronik ürtikerli olgularımızın etyolojik değerlendirmesi

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