Studies of Cicatricial Pemphigoid Autoantibodies Using Direct Immunoelectron Microscopy and Immunoblot Analysis

Bernard, Philippe; Prost, Cathérine; Lecerf, V.; Intrator, L; Combemale, P.; Bédane, C.; Roujeau, Jean‐Claude; Revuz, J; Bonnetblanc, Jean-Marie; Dubertret, Louis

doi:10.1111/1523-1747.ep12876206

Cited by 145 publications

(76 citation statements)

References 25 publications

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“…Mucous membrane pemphigoid is a clinical phenotype that encompasses several subsets, with a wide spectrum of clinical presentation, clinical course, and prognosis. In our study, determination of patients' autoantibody profiles using commercial ELISAs allowed us to confirm that BP180 is a major autoantigen in MMP, as previously demonstrated by many studies [6][7][8][9]16,27,34,[40][41][42] performed in the past 2 decades and based on immunoblot analysis using human epidermal, amniotic membrane, or fusion proteins. These studies showed that circulating IgG autoantibodies from patients with MMP can recognize several intracellular and extracellular BP180 epitopes, sometimes distinct from the NC16A domain.…”

Section: Commentsupporting

confidence: 82%

“…Mucous membrane pemphigoid is associated with significant morbidity, potentially leading to definitive functional sequelae, especially in ocular or upper aerodigestive tract manifestations. 4,5 Patients with MMP exhibit, although inconsistently, circulating autoantibodies directed against various components of the dermal-epidermal/ chorioepithelial BMZ 6 including bullous pemphigoid (BP) 180 antigens [7][8][9][10] and BP230 antigens, 7,11 laminin (Lam) 332 an-tigens, [12][13][14] the 97/120-kDa linear IgA bullous disease antigen, type VII collagen, and the integrin ␤ 4 antigen. 15 The 2 major autoantigens of MMP are BP180, mainly its extracellular domain, 16,17 and Lam332; both are components of anchoring filaments and reach into the lamina densa of the BMZ.…”

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confidence: 99%

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Prevalence and Clinical Significance of Anti–Laminin 332 Autoantibodies Detected by a Novel Enzyme-Linked Immunosorbent Assay in Mucous Membrane Pemphigoid

Bernard

Antonicelli²,

Bédane³

et al. 2013

JAMA Dermatol

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Importance:A rare variant of mucous membrane pemphigoid (MMP) is characterized by circulating antilaminin 332 (Lam332) autoantibodies and seems to be associated with concurrent malignant neoplasms.Objective: To determine the prevalence and clinical significance of anti-Lam332 autoantibody detection from a large series of patients with MMP.Design: Multicenter retrospective study. Interventions: Serum samples were analyzed by a new Lam332 enzyme-linked immunosorbent assay (ELISA); clinical and immunopathologic data were obtained from the patients' medical records. Main Outcome Measures:The Lam332 ELISA scores were evaluated with respect to clinical characteristics, standard and salt-split indirect immunofluorescence, and bullous pemphigoid (BP) 230 and BP180-NC16A ELISAs.Results: The Lam332 ELISA score was positive (Ն9 U/mL) in 20.1% of serum samples from patients with MMP, 1 of 50 patients with bullous pemphigoid (BP), none of 7 with pemphigus, and 3 of 32 other controls. No relationship was evidenced between a positive ELISA Lam332 score and age; sex ratio; oral, ocular, genital, skin, or esophageal/laryngeal involvement; internal malignant neoplasm; or BP180 ELISA score. Salt-split skin indirect immunofluorescence and ELISA BP230 results were more frequently positive when Lam332 ELISA results were positive (P=.04 and .02, respectively). Patients with a positive Lam332 ELISA score frequently had more severe MMP (67.8% vs 47.2%; P=.04). Conclusions and Relevance:Results of this novel ELISA showed that serum anti-Lam332 autoantibodies are detected in 20.1% of patients with MMP. AntiLam332 autoantibodies are mainly detected in patients with severe MMP but not preferentially in those with a malignant neoplasm. The association between antiLam332 and anti-BP230 autoantibodies might arise from an epitope-spreading phenomenon.

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Section: Commentsupporting

confidence: 82%

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confidence: 99%

Prevalence and Clinical Significance of Anti–Laminin 332 Autoantibodies Detected by a Novel Enzyme-Linked Immunosorbent Assay in Mucous Membrane Pemphigoid

Bernard

Antonicelli²,

Bédane³

et al. 2013

JAMA Dermatol

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“…31 The specificity of immunoblotting is insufficient 29 : there is an overlap between BP and CP, since a 180-kd protein is detected in 19% to 50% of the serum samples of patients with BP 9,10,24,30-41 and in 40% to 70% of the serum samples of patients with CP. 9,10 On the other hand, the sensitivity and specificity of immunoprecipitation has not yet been evaluated in a prospective series of patients with BP. In the patients in whom no circulating antibodies are detected, direct immunofluorescence on salt-split skin by means of biopsy specimens of perilesional skin 42,43 makes it possible to rule out the diagnosis of EBA if IgG appeared on the epidermal side of the blister, 42 but not to separate BP and CP, since in CP, IgG may appear on both the epidermal and the dermal sides.…”

Section: Discussionmentioning

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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“…Several auto-antibodies against epithelial basement membrane antigens have been discovered in patients with MMP, including bullous pemphigoid antigens 1 and 2, laminin 5 and 6, type 7 collagen, integrin ␤4 subunit, and as-yet unidentified antigens (a 45-kDa protein, uncein, a 168-kDa protein, and a 120-kDa protein). 1,[20][21][22][23] It is hypothesized that a genetic predisposition, as demonstrated by the association of human leukocyte antigen-DQB1*0301 with MMP 24 along with an environmental trigger, results in the production of auto-antibodies against these antigens, 1 resulting in deposition of IgG, IgA, and complement 3 at the epithelial basement membrane.…”

Section: Commentmentioning

confidence: 99%

Successful Treatment of Mucous Membrane Pemphigoid With Etanercept in 3 Patients

Canizares

Smith²,

Conners³

et al. 2006

Arch Dermatol

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Studies of Cicatricial Pemphigoid Autoantibodies Using Direct Immunoelectron Microscopy and Immunoblot Analysis

Cited by 145 publications

References 25 publications

Prevalence and Clinical Significance of Anti–Laminin 332 Autoantibodies Detected by a Novel Enzyme-Linked Immunosorbent Assay in Mucous Membrane Pemphigoid

Prevalence and Clinical Significance of Anti–Laminin 332 Autoantibodies Detected by a Novel Enzyme-Linked Immunosorbent Assay in Mucous Membrane Pemphigoid

Evaluation of Clinical Criteria for Diagnosis of Bullous Pemphigoid

Successful Treatment of Mucous Membrane Pemphigoid With Etanercept in 3 Patients

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