IgA basement membrane zone autoantibodies in bullous pemphigoid detect epidermal antigens of 270-280 kDa, 230 kDa, and 180 kDa molecular weight by immunoblotting

Abstract

Bullous pemphigoid (BP) is an acquired subepidermal blistering disease characterized by circulating IgG autoantibodies binding to the 230 and 180 kDa hemidesmosomal proteins. Associated basement membrane zone (BMZ) autoantibodies of the IgA class have been reported in few BP patients. The incidence and clinical relevance of these IgA antibodies, as well as their target antigens are unknown. Sera of 26 patients with BP were analysed for circulating IgG- and IgA-anti-BMZ autoantibodies by indirect immunofluorescence on salt-split human skin. All of the patients had circulating IgG autoantibodies and, in addition, nine (35%) also had circulating anti-BMZ IgA antibodies, that bound to the epidermal side of salt-split skin. By immunoblotting, IgA antibodies in seven of nine sera recognized either the 180 kDa, the 230 kDa, or both BP antigens. Moreover, IgA anti-BMZ antibodies in seven sera also detected an epidermal protein of 270-280 kDa. IgA antibodies did not identify specific bands on immunoblots of dermal extracts. There was no clinical difference between BP patients with or without circulating anti-BMZ-IgA.

Patients with Bullous Pemphigoid and Linear IgA Disease show a Dual IgA and IgG Autoimmune Response to BP180

“…Infrequently, the target antigens have been characterized in patients with both IgA and IgG anti-BMZ autoantibodies [27,[31][32][33]42]. In the present study we demonstrate that the concurrent appearance of IgA and IgG autoantibodies to BP180 is a common finding in sera from patients with BP and LAD.…”

“…By indirect immunofluorescence microscopy, a small number of studies found both IgA and IgG anti-BMZ autoantibodies in BP patients [24][25][26][27]. Similarly, there are few reports of LAD patients demonstrating both IgA and IgG anti-BMZ antibodies [28,29]; the term linear IgA/IgG bullous dermatosis was proposed for this disease [30].…”

“…Similarly, there are few reports of LAD patients demonstrating both IgA and IgG anti-BMZ antibodies [28,29]; the term linear IgA/IgG bullous dermatosis was proposed for this disease [30]. However, in only a minority of patients with both IgA and IgG anti-BMZ antibodies were the target antigen(s) identified [27,[30][31][32][33]42].…”

Mixed immunobullous disease of childhood: a good response to antimicrobials

“…6,7 In BP, linear IgG is found at the BMZ and treatment with systemic steroids is nearly always required to achieve control. 10 These bound to the two known BP antigens and also to a 270±280-kDa epidermal protein, suggesting an overlap between BP and linear IgA disease (LAD) with regard to target antigens. Some of these patients, and those with EBA and CP, have been previously reported.…”

Linear Immunoglobulin A Bullous Dermatosis: Need for an Agreement on Diagnostic Criteria

“…Moreover, to define predominance of IgA based on immunofluorescence staining intensity is very complicated, since the staining intensity critically depends on the experimental conditions, including dilution and type of the second step antibodies used for detection of the tissue-bound deposits. This question becomes more important considering that linear IgA deposits have been reported in several cases of subepidermal blistering diseases other than LABD, including BP [11] , mucous membrane pemphigoid (MMP) [12] , pemphigoid gestationis [13] and EBA [14] . Another important question about the immunopathological features of LABD concerns the presence of circulating IgA antibodies against BMZ antigens.…”