Development of an ELISA for sensitive and specific detection of IgA autoantibodies against BP180 in pemphigoid diseases

Csorba, Kinga; Schmidt, Sabine; Florea, Florina; Ishii, Norito; Hashimoto, Takashi; Hertl, Michael; Kárpáti, Sarolta; Bruckner‐Tuderman, Leena; Nishie, Wataru; Sitaru, Cassian

doi:10.1186/1750-1172-6-31

Cited by 39 publications

(40 citation statements)

References 59 publications

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“…This result complements that of our study, in which a significant number of BP sera possessed IgA antibodies reactive with recombinant protein of LAD-1 by ELISA (Csorba et al, 2011). In four patients in the present study, IgG reactivity with BP180 and BP230 spread to IgA reactivity with LAD-1.…”

Section: This Study Indicated Clinical Significance Of Es Events In Bpsupporting

confidence: 90%

Demonstration of Epitope Spreading in Bullous Pemphigoid: Results of a Prospective Multicenter Study

Hashimoto

Tsuruta

Dainichi

et al. 2011

Journal of Investigative Dermatology

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Di Zenzo and colleagues have undertaken a multicenter prospective study to clarify the epitope profile for IgG anti-BP180 and BP230 antibodies in 35 patients with bullous pemphigoid (BP). Both intra- and intermolecular epitope spreading events were observed, in which epitopes shifted exclusively from extracellular to intracellular domains. The presence of IgG antibodies to the BP180 C-terminal domain and BP230, in addition to the BP180-NC16A domain, correlated with disease severity and activity, suggesting specific pathogenic relevance for anti-BP230 antibodies. Epitope spreading was found in both T- and B-cell recognition. IgA anti LAD-1 antibodies are frequently found in patients with BP; these antibodies appear to follow the development of IgG antibodies to BP180 and BP230 by epitope spreading. These observations provide direction for future studies of the pathogenesis of and treatments for BP.

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Section: This Study Indicated Clinical Significance Of Es Events In Bpsupporting

confidence: 90%

Demonstration of Epitope Spreading in Bullous Pemphigoid: Results of a Prospective Multicenter Study

Hashimoto

Tsuruta

Dainichi

et al. 2011

Journal of Investigative Dermatology

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“…An entity of the pemphigoid group is the lamina lucida type of linear IgA disease (IgA pemphigoid), characterized by IgA autoantibodies against BP180. Csorba et al [20] strongly suggest that IgA pemphigoid and IgG BP are the two endpoints of the clinical spectrum of an immunological loss of tolerance against the components of hemidesmosomes, mediated by both IgG and IgA autoantibodies [20]. Previous studies have demonstrated that BP autoantibodies react predominantly with two distinct proteins of the hemidesmosomes, BP230, and BP180 [6].…”

Section: Resultsmentioning

confidence: 99%

Clinical Relevance of Autoantibodies in Patients with Autoimmune Bullous Dermatosis

Mihályi

Kiss

Kemény

et al. 2012

Clinical and Developmental Immunology

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The authors present their experience related to the diagnosis, treatment, and followup of 431 patients with bullous pemphigoid, 14 patients with juvenile bullous pemphigoid, and 273 patients with pemphigus. The detection of autoantibodies plays an outstanding role in the diagnosis and differential diagnosis. Paraneoplastic pemphigoid is suggested to be a distinct entity from the group of bullous pemphigoid in view of the linear C3 deposits along the basement membrane of the perilesional skin and the “ladder” configuration of autoantibodies demonstrated by western blot analysis. It is proposed that IgA pemphigoid should be differentiated from the linear IgA dermatoses. Immunosuppressive therapy is recommended in which the maintenance dose of corticosteroid is administered every second day, thereby reducing the side effects of the corticosteroids. Following the detection of IgA antibodies (IgA pemphigoid, linear IgA bullous dermatosis, and IgA pemphigus), diamino diphenyl sulfone (dapsone) therapy is preferred alone or in combination. The clinical relevance of autoantibodies in patients with autoimmune bullous dermatosis is stressed.

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“…The identification of target antigens in the great majority of autoimmune bullous diseases has led to the development of standardized specific and sensitive diagnostic assays, some of them have been commercialized [17,19-23,30,32,34-37,41-45] (Table 1). By the use of these assays, exact diagnosis can be made, which is of both prognostic and therapeutic relevance.…”

Section: Discussionmentioning

confidence: 99%

Serological diagnosis of autoimmune bullous skin diseases: Prospective comparison of the BIOCHIP mosaic-based indirect immunofluorescence technique with the conventional multi-step single test strategy

Beek

Rentzsch

Probst

et al. 2012

Orphanet J Rare Dis

118

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BackgroundVarious antigen-specific immunoassays are available for the serological diagnosis of autoimmune bullous diseases. However, a spectrum of different tissue-based and monovalent antigen-specific assays is required to establish the diagnosis. BIOCHIP mosaics consisting of different antigen substrates allow polyvalent immunofluorescence (IF) tests and provide antibody profiles in a single incubation.MethodsSlides for indirect IF were prepared, containing BIOCHIPS with the following test substrates in each reaction field: monkey esophagus, primate salt-split skin, antigen dots of tetrameric BP180-NC16A as well as desmoglein 1-, desmoglein 3-, and BP230gC-expressing human HEK293 cells. This BIOCHIP mosaic was probed using a large panel of sera from patients with pemphigus vulgaris (PV, n = 65), pemphigus foliaceus (PF, n = 50), bullous pemphigoid (BP, n = 42), and non-inflammatory skin diseases (n = 97) as well as from healthy blood donors (n = 100). Furthermore, to evaluate the usability in routine diagnostics, 454 consecutive sera from patients with suspected immunobullous disorders were prospectively analyzed in parallel using a) the IF BIOCHIP mosaic and b) a panel of single antibody assays as commonly used by specialized centers.ResultsUsing the BIOCHIP mosaic, sensitivities of the desmoglein 1-, desmoglein 3-, and NC16A-specific substrates were 90%, 98.5% and 100%, respectively. BP230 was recognized by 54% of the BP sera. Specificities ranged from 98.2% to 100% for all substrates. In the prospective study, a high agreement was found between the results obtained by the BIOCHIP mosaic and the single test panel for the diagnosis of BP, PV, PF, and sera without serum autoantibodies (Cohen’s κ between 0.88 and 0.97).ConclusionsThe BIOCHIP mosaic contains sensitive and specific substrates for the indirect IF diagnosis of BP, PF, and PV. Its diagnostic accuracy is comparable with the conventional multi-step approach. The highly standardized and practical BIOCHIP mosaic will facilitate the serological diagnosis of autoimmune blistering diseases.

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Development of an ELISA for sensitive and specific detection of IgA autoantibodies against BP180 in pemphigoid diseases

Cited by 39 publications

References 59 publications

Demonstration of Epitope Spreading in Bullous Pemphigoid: Results of a Prospective Multicenter Study

Demonstration of Epitope Spreading in Bullous Pemphigoid: Results of a Prospective Multicenter Study

Clinical Relevance of Autoantibodies in Patients with Autoimmune Bullous Dermatosis

Serological diagnosis of autoimmune bullous skin diseases: Prospective comparison of the BIOCHIP mosaic-based indirect immunofluorescence technique with the conventional multi-step single test strategy

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