Identification of a Potential Effector Function for IgE Autoantibodies in the Organ-Specific Autoimmune Disease Bullous Pemphigoid

Abstract

Bullous pemphigoid (BP) is an autoimmune skin disease characterized by autoantibodies against the hemidesmosomal protein BP180. In addition to IgG autoantibodies, IgE class autoantibodies have been reported in BP patients. Because animal models utilizing only IgG antibodies do not totally replicate human BP, we examined the specificity and potential relevance of IgE autoantibodies in this disease. Thirty BP patients participated in these studies. Serum IgE was measured and the IgE specificity was determined by immunoblotting. Double labeling Immunofluorescence was performed using combinations of specific antibodies to human mast cell tryptase, IgE and BP180. BP180-stimulated histamine release was measured from basophils of untreated BP patients (n=9), BP patients undergoing immunosuppressive therapy (n=9) and controls (n=16). Elevated IgE levels were found In 70% of untreated BP patients. IgE autoantibodies directed against BP180 were detected in 86% of untreated patients and in all but one of these patients the IgE reacted with the NC16A domain of BP180. IgE-coated mast cells were detected in perilesional skin of the BP patients. Moreover, BP180 peptides were detected on these mast cells. BP180-stimulated histamine release was significantly higher in basophils obtained from untreated BP patients compared with control basophils (p=0.006) or from treated BP patients (p=0.01). These findings support the hypothesis that IgE autoantibodies are involved in the pathogenesis of BP. IgE and IgG BP autoantibodies share the same antigenic specificity. Antigen-specific degranulation of basophils and/or mast cells from BP patients suggests a mechanism by which IgE may contribute to lesion development.

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

“…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.…”

What’s new in bullous pemphigoid

“…40 In clinical terms, total IgE levels are elevated in 70% of untreated BP patients and IgE autoantibodies against COL17 are detected in 86% of untreated BP patients. 41 Iwata et al 42 reported that the presence of IgE autoantibodies against COL17 was associated with a severe form of BP, and BP patients with IgE anti-COL17 antibodies required a longer period of treatment for remission, a higher dose of prednisolone, and more intensive treatments for remission. These findings suggest that IgE autoantibodies against COL17 are associated with BP pathogenesis and disease activity.…”

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

“…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] .…”