Analysis of antigens targeted by circulating IgG and IgA autoantibodies in 50 patients with cicatricial pemphigoid

Murakami, H; Nishioka, Shoji; Setterfield, Jane; Bhogal, B.S.; Black, Martin M.; Zillikens, Detlef; Yancey, Kim B.; Balding, Shawn D.; Giudice, George J.; Díaz, Luis A.; Nishikawa, Takeji; Kiyokawa, Chie; Hashimoto, Takashi

doi:10.1016/s0923-1811(97)00067-4

Cited by 95 publications

(109 citation statements)

References 31 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%

“…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. 6,34,41,42 Using a panel of cell-derived and recombinant proteins covering the entire BP180 molecule, Schmidt et al 41 found that 19 of 26 MMP serum samples recognized BP180, including 6 (32%) that showed only IgA reactivity to this autoantigen. By immunoblotting using human epidermal, dermal, and placental amnion proteins of a large series of MMP, Oyama et al 34 similarly showed that most patients with MMP (75%) had IgG to BP180, including its soluble ectodomains.…”

Section: Commentmentioning

confidence: 99%

“…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%

Section: Commentmentioning

confidence: 99%

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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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“…18 Second, when artificial blistering of human skin is induced by 1 mol/L NaCl, collagen XVII separates to the epidermal side of the blister and not to the dermal side with laminin 332. 33,34 Also, the Ab HK139 detected the shed Ecto-ColXVII on the epidermal side of 1 mol/L NaCl split skin, 17 suggesting that yet other epidermisassociated molecules interact with the Ecto-ColXVII. Future studies will elucidate these binding partners.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Interactions of Epidermal Collagen XVII with the Extracellular Matrix

Nishie

Kiritsi

Nyström

et al. 2011

The American Journal of Pathology

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“…However, BP patients’ sera may also have antibodies that recognize epitopes distal to this domain, including the C-terminal domain in some patients [15, 16, 17, 18]. BP patients’ sera can also recognize distinct epitopes on the intracellular domain of BPAg2 [19].…”

Section: Discussionmentioning

confidence: 99%

The Immunoglobulin A Antibody Response in Clinical Subsets of Mucous Membrane Pemphigoid

et al. 1999

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Background: Mucous membrane pemphigoid (MMP) is an immunobullous disease. In MMP there is frequently a mixed antibody response with the presence of IgA and/or IgG antibodies directed toward basement membrane zone antigens. The IgG antibody response in MMP has been studied, but the antigens to which the IgA antibodies react have not been studied. Objective: To determine the IgA autoantibody reactivity profiles in patients with MMP. Methods: Patients who had both ocular and oral MMP were compared with patients who had ocular or oral MMP and with patients who had cutaneous linear IgA disease (LABD) by Western immunoblot studies. Results: Five of 15 MMP patients and 1 of 5 LABD patients had IgA antibodies reactive with the 180-kD bullous pemphigoid antigen. Seven of 15 MMP patients had IgA antibodies reactive with the 97-kD LABD antigen. Conclusion: Major antigens in IgA MMP are the 180-kD bullous pemphigoid antigen and the 97-kD LABD antigen.

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Analysis of antigens targeted by circulating IgG and IgA autoantibodies in 50 patients with cicatricial pemphigoid

Cited by 95 publications

References 31 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

Dynamic Interactions of Epidermal Collagen XVII with the Extracellular Matrix

The Immunoglobulin A Antibody Response in Clinical Subsets of Mucous Membrane Pemphigoid

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