Cicatricial Pemphigoid Antigen Differs from Bullous Pemphigoid Antigen by Its Exclusive Extracellular Localization: A Study by Indirect Immunoelectronmicroscopy

Bédane, C.; Prost, Cathérine; Bernard, Philippe; Catanzano, G; Bonnetblanc, Jean-Marie; Dubertret, Louis

doi:10.1111/1523-1747.ep12477198

Cited by 70 publications

(30 citation statements)

References 28 publications

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“…We have previously proposed a set of 4 clinical criteria from a logistic-stepwise multivariate analysis, that allowed to diagnose BP with a positive predictive value between 95 and 98% [26]. IEM was used as the criterion standard to distinguish BP from other AIBDs because ultrastructural localization of immune deposits allows clear differentiation between BP, CP and EBA [14, 28, 29, 30]. However, the validity of this set of criteria has been questioned because IEM does not really identify the antigens recognized by patient sera [31].…”

Section: Discussionmentioning

confidence: 99%

“…We found that the diagnosis of BP could be made with a sensitivity of 90% and a specificity of 83% if patients had 3 of these 4 criteria [27]. In this study, IEM was used as the criterion standard because it allows the ultrastructural location of IgG and/or C3 deposits [14, 28, 29, 30]. However, IEM alone without the addition of immunoblotting or ELISA is not unanimously accepted as the diagnostic criterion standard because it does not identify the antigenic specificities recognized by anti-basement-membrane-zone (BMZ) antibodies [31].…”

Section: Introductionmentioning

confidence: 99%

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Clinical Criteria for the Diagnosis of Bullous Pemphigoid: A Reevaluation according to Immunoblot Analysis of Patient Sera

et al. 2004

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Background: We previously proposed a set of 4 clinical criteria for the diagnosis of bullous pemphigoid (BP) that consisted of age greater than 70 years, absence of atrophic scars, absence of mucosal involvement and absence of predominant bullous lesions on the neck and head. These results have been challenged because direct immunoelectron microscopy (IEM), which was used as the standard diagnostic criterion in our initial study, does not identify the different antigens of the basement membrane zone. Objective: To reassess the validity of these clinical criteria for the diagnosis of BP using immunoblot analysis of patient sera as the main diagnostic criterion, in order to precisely identify the antigens recognized by patient sera. Methods: One hundred and eighty-nine sera from patients with various subepidermal autoimmune blistering diseases (AIBDs) were tested by immunoblotting using dermal and epidermal extracts. IEM was used as a complementary diagnostic procedure in a few patients whose serum recognized BPAG2 exclusively or was negative in immunoblotting. Results: 142 patients (75%) had at least 3 of the 4 clinical diagnostic criteria. Sera from patients who lacked the set of BP clinical criteria were more frequently immunoblot negative (34%) than sera from patients who had the criteria (18%; p = 0.025). BPAG1 was more frequently recognized by sera from patients with the set of BP clinical criteria (78%) than by sera from patients without the criteria (45%; p = 5·10^–4). In contrast, BPAG2 was recognized by a great number of sera from patients who lacked the criteria of BP (71%), which was in accordance with the presence of numerous patients with cicatricial pemphigoid in this group. Among patients with various subepidermal AIBDs, the diagnosis of BP could be made with a sensitivity of 86%, a specificity of 90% and an excellent prognostic positive value over 95%, if 3 of these clinical criteria were present. Conclusion: These results confirm the interest of this set of clinical criteria for the rapid diagnosis of BP.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical Criteria for the Diagnosis of Bullous Pemphigoid: A Reevaluation according to Immunoblot Analysis of Patient Sera

et al. 2004

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“…Clinical findings were prospectively recorded by means of the same standardized questionnaire that had been used in previous studies. [14][15][16] Examination by IEM was performed by a previously described technique. 17 Two hundred thirty-one patients met the inclusion criteria and had IEM examination.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of Clinical Criteria for Diagnosis of Bullous Pemphigoid

Vaillant¹

1998

Arch Dermatol

170

132

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To check the potential usefulness of clinical criteria for the diagnosis of bullous pemphigoid when state-of-the-art techniques such as Western immunoblotting, immunoprecipitation, and indirect immunofluorescence on salt-split skin or direct immunoelectron microscopy are not available.Design: Comparison of the clinical criteria between 2 groups (with and without bullous pemphigoid) as defined by immunoelectron microscopy used as standard criterion, in a prospective study. Multivariate logistic regression analysis was carried out by including all items that were statistically significant (at PϽ.05 level) in univariate analysis.Setting: Five dermatology departments in teaching hospitals. Patients:The 231 patients studied had subepidermal autoimmune bullous diseases with linear IgG or C3 deposits in the basement membrane zone (157 with bullous pemphigoid, 33 with cicatricial pemphigoid, 30 with epidermolysis bullosa acquisita, 5 with lupus erythem-atosus, and 6 others). A second set of patients was used to calculate predictive values. Results:The multivariate logistic stepwise analysis resulted in a final set of predictors that included only 4 items: absence of atrophic scars, absence of head and neck involvement, absence of mucosal involvement, and age greater than 70 years. No additional variables met the .05 significance level to enter into the model. If 3 of these 4 characteristics were present, a diagnosis of bullous pemphigoid could be made with a sensitivity of 90% and a specifity of 83%; these predictive values were calculated on a sample of 70 new cases.Conclusions: With an estimated incidence of bullous pemphigoid among subepidermal autoimmune bullous diseases of 80%, the presence of 3 of the 4 significant criteria allows the diagnosis of bullous pemphigoid, with a positive predictive value of 95%. Our set of' clinical criteria thus allows the diagnosis of bullous pemphigoid with good validity for both clinical practice and therapeutic trials.

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“…The sera used by two investigators bound to the dermal side of salt split skin on indirect immunofluorescence assay and lamina densa on IEM contained Abs to laminin-5 (34). In the second group, investigators demonstrate that immunodeposits occur on hemidesmosomes and basal keratinocyte cytoplasm or the junction between hemidesmosomes and the inner plasma membrane of keratinocytes (33)(34)(35). These investigators observed that sera that produced such immune deposition did not contain Abs to laminin-5 or BP (33).…”

Section: Discussionmentioning

confidence: 99%

The Autoantibodies to α6β4 Integrin of Patients Affected by Ocular Cicatricial Pemphigoid Recognize Predominantly Epitopes Within the Large Cytoplasmic Domain of Human β4

Bhol

Dans

Simmons

et al. 2000

The Journal of Immunology

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This study was undertaken to characterize the antigenic determinants recognized by the autoantibodies of patients with ocular cicatricial pemphigoid (OCP). OCP is a subepithelial, blistering, autoimmune disease that mainly affects the conjunctiva and other mucous membranes. We previously demonstrated that a cDNA clone, isolated from a keratinocyte expression library by using immunoaffinity-purified OCP autoantibody, encoded the cytoplasmic domain of β4 integrin subunit. Our subsequent studies showed that sera from all the OCP patients that were tested recognize the human β4 integrin subunit. To identify the prevalent epitopes of the anti-β4 autoantibodies of OCP, we have used cell lines transfected with vectors encoding a wild-type β4 subunit, a tailless β4 subunit, or a β4 subunit lacking the extracellular domain. Nontransfected cell lines were used as controls. Lysates from these cell lines were analyzed with OCP sera, IgG fractions from OCP sera, and immunoaffinity-purified OCP autoantibodies. Abs to extracellular and cytoplasmic domains of human β4 integrin were used as positive controls, whereas normal human sera and normal human IgG fractions were used as negative controls. The reactivity of OCP Abs was determined by using immunoblotting, immunoprecipitation, and FACS analysis. The results of this study indicate that OCP sera, OCP IgG fractions, and immunoaffinity-purified OCP autoantibodies react with the intracellular and not the extracellular domain of human β4 integrin subunit. In vitro cell culture experiments demonstrated that OCP autoantibody binds to the cytoplasm of the cells. The relevance of these findings to the pathogenesis of OCP is discussed.

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Cicatricial Pemphigoid Antigen Differs from Bullous Pemphigoid Antigen by Its Exclusive Extracellular Localization: A Study by Indirect Immunoelectronmicroscopy

Cited by 70 publications

References 28 publications

Clinical Criteria for the Diagnosis of Bullous Pemphigoid: A Reevaluation according to Immunoblot Analysis of Patient Sera

Clinical Criteria for the Diagnosis of Bullous Pemphigoid: A Reevaluation according to Immunoblot Analysis of Patient Sera

Evaluation of Clinical Criteria for Diagnosis of Bullous Pemphigoid

The Autoantibodies to α6β4 Integrin of Patients Affected by Ocular Cicatricial Pemphigoid Recognize Predominantly Epitopes Within the Large Cytoplasmic Domain of Human β4

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