A Pathogenic Role for IgE in Autoimmunity: Bullous Pemphigoid IgE Reproduces the Early Phase of Lesion Development in Human Skin Grafted to nu/nu Mice

Fairley, Janet A.; Burnett, Christopher T.; Fu, Chang-Ling; Larson, David L.; Fleming, Matthew G.; Giudice, George J.

doi:10.1038/sj.jid.5700958

Cited by 154 publications

(139 citation statements)

References 37 publications

(36 reference statements)

Supporting

Mentioning

133

Contrasting

Unclassified

Order By: Relevance

“…These processes are probably a reflection of their "physiological" role in the control of parasitic infections, which can also be associated with higher IgE levels, an activated mast cell phenotype, and the persistent presence of antigen. A role for antigen-specific IgE in autoimmunity has previously been demonstrated (14,15). Bullous pemphigoid (BP) is an autoimmune skin disease characterized by subepidermal blistering.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Evidence for a functional role of IgE anticitrullinated protein antibodies in rheumatoid arthritis

Schuerwegh¹,

Ioan‐Facsinay²,

Dorjée³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is a systemic autoimmune disease involving inflammation of the joints. Among the autoantibodies described in RA, anticitrullinated protein antibodies (ACPAs) are highly specific and predictive for RA. In addition, ACPAs have been implicated in the pathogenesis of RA. However, a direct functional response of immune cells from ACPA + RA patients toward citrullinated proteins has not been demonstrated. In this study, we show that exposure to citrullinated antigens leads to activation of basophils from ACPA + RA patients within 20 minutes. This was not observed after exposure of basophils to noncitrullinated control antigens or after stimulation of basophils from ACPA − RA patients and healthy controls. Basophil activation was correlated with the binding of citrullinated proteins to basophils. Furthermore, serum from ACPA + RA patients in contrast to that from ACPA − RA patients could specifically sensitize human FcεRI expressing rat basophil cells (RBL), enabling activation by citrullinated proteins. Mast cell degranulation products such as histamine levels were enhanced in synovial fluid of ACPA + RA patients as compared with ACPA − RA and osteoarthritis patients. In addition, histamine levels in synovial fluid from ACPA + RA patients correlated with IgE levels, suggesting degranulation of mast cells by cross-linking IgE. Immunohistochemistry on synovial biopsies demonstrated an increased number of degranulated CD117 + mast cells in ACPA + RA patients; IgE and FcεRI expression in synovial mast cells from ACPA + RA patients was increased. In conclusion, our results show an immunological response of immune cells from ACPA + RA patients in a citrulline-specific manner. Moreover, these data indicate a role for IgE-ACPAs and FcεRI-positive cells in the pathogenesis of RA.

show abstract

Section: Discussionmentioning

confidence: 99%

RETRACTED: Evidence for a functional role of IgE anticitrullinated protein antibodies in rheumatoid arthritis

Schuerwegh¹,

Ioan‐Facsinay²,

Dorjée³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…BP180 proteininin NC16A bölgesini hedefleyen IgE antikorların tespit edildiği çalışmalar ve bu antikorların erken dönem BP lezyonlarının oluşumundaki patojenik rolüne ilişkin ilerleyen bilgilere göre, BP için yeni bir terapötik seçenek ortaya çıkmıştır 16,22,23 . Hastalarımızın tamamı yaygın klasik hastalık tablosuna ve önemli komorbiditelere sahipti.…”

Section: Discussionunclassified

“…İnsan monoklonal anti-IgE otoantikoru olan omalizumab (OMZ), immün hücreler üzerinde IgE ekspresyonunu azaltarak ve IgE'nin reseptörüne bağlanmasını önleyerek mast hücreleri ve bazofiller üzerinde IgE etkisini nötralize etmiş olur 13,14 . Tedavi edilmemiş BP hastalarının çoğunda artmış dolaşan IgE seviyesi ve aynı ekstrasellüler non-kollajenöz 16A (NC16A) bölgesini esas olarak hedef alan IgE otoantikorları gösterilmiştir [15][16][17] . Geçtiğimiz yıllarda BP patomekanizmasındaki IgE'nin kritik rolünü ortaya koyan deneysel çalışmalara göre, IgE/IgE reseptör etkileşiminin inhibisyonu hastalığın tedavisinde umut verici bir tedavi seçeneği olmuştur [18][19][20][21] .…”

Section: Introductionunclassified

Our clinical experience with the use of omalizumab in the treatment of bullous pemphigoid

Uysal¹,

Yalçın²,

Öktem³

2017

TURKDERM

View full text Add to dashboard Cite

Background and Design:In the era of biological therapies, omalizumab (OMZ), a monoclonal antibody which inhibits IgE, has been postulated to be effective in the treatment of bullous pemphigoid (BP). We report our clinical experience with the use of OMZ in the treatment of BP. Materials and Methods: Retrospective data analyses of eleven patients were performed. Results: Seven patients receiving OMZ treatment demonstrated clinical improvements. Three patients terminated treatment because of intermittent co-morbidities. None of the patients had any significant adverse events. Conclusion: OMZ may be a promising corticosteroid-sparing treatment option for moderate to severe BP patients. Future randomized controlled trials are indicated to evaluate the efficacy of OMZ in the treatment of BP. Büllöz pemfigoid tedavisinde omalizumab kullanımı üzerine klinik deneyimlerimiz

show abstract

“…Although inflammation and skin fragility at the level of the BMZ were observed in the IgG passive transfer models, other hallmarks of BP that were absent included urticarial plaque formation, recruitment of eosinophils, and spontaneous subepidermal blistering (6,7,14). These shortcomings of the IgG-based models led to investigations into the role of IgE class autoantibodies in the BP disease process (17,(19)(20)(21). Passive transfer of IgE autoantibodies, purified from patient sera, into human skin grafts on nude mice was shown to induce lesions in the grafted skin that reproduce the early phases of BP lesion development, including mast cell degranulation, eosinophil influx, formation of erythematous plaques, and histological separation at the BMZ (19).…”

mentioning

confidence: 99%

FcR-Independent Effects of IgE and IgG Autoantibodies in Bullous Pemphigoid

Messingham

Srikantha

DeGueme

et al. 2011

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Bullous pemphigoid (BP) is a subepidermal blistering disease characterized by IgE and IgG class autoantibodies specific for 180-kDa BP Ag 2 (BP180), a protein involved in cell-substrate attachment. Although some direct effects of BP IgG have been observed on keratinocytes, no study to date has examined direct effects of BP IgE. In this study, we use primary cultures of human keratinocytes to demonstrate Ag-specific binding and internalization of BP IgE. Moreover, when BP IgE and BP IgG were compared, both isotypes stimulated FcR- independent production of IL-6 and IL-8, cytokines critical for BP pathology, and elicited changes in culture confluence and viability. We then used a human skin organ culture model to test the direct effects of these Abs on the skin, whereas excluding the immune inflammatory processes that are triggered by these Abs. In these experiments, physiologic concentrations of BP IgE and BP IgG exerted similar effects on human skin by stimulating IL-6 and IL-8 production and decreasing the number of hemidesmosomes localized at the basement membrane zone. We propose that the Ab-mediated loss of hemidesmosomes could weaken attachment of basal keratinocytes to the basement membrane zone of affected skin, thereby contributing to blister formation. In this article, we identify a novel role for IgE class autoantibodies in BP mediated through an interaction with BP180 on the keratinocyte surface. In addition, we provide evidence for an FcR-independent mechanism for both IgE and IgG class autoantibodies that could contribute to BP pathogenesis.

show abstract

A Pathogenic Role for IgE in Autoimmunity: Bullous Pemphigoid IgE Reproduces the Early Phase of Lesion Development in Human Skin Grafted to nu/nu Mice

Cited by 154 publications

References 37 publications

RETRACTED: Evidence for a functional role of IgE anticitrullinated protein antibodies in rheumatoid arthritis

RETRACTED: Evidence for a functional role of IgE anticitrullinated protein antibodies in rheumatoid arthritis

Our clinical experience with the use of omalizumab in the treatment of bullous pemphigoid

FcR-Independent Effects of IgE and IgG Autoantibodies in Bullous Pemphigoid

Contact Info

Product

Resources

About