Anti‐laminin‐332 mucous membrane pemphigoid with autoantibodies to α3, β3 and γ2 subunits of laminin‐332 as well as to <scp>BP</scp>230 and periplakin associated with adenocarcinoma from an unknown primary site

Fukuchi, Osamu; Suko, Ayana; Matsuzaki, Hiroyuki; Baba, Hiromi; Yoshida, Hisatoshi; Takeuchi, Tomokazu; Odawara, Syunichi; Fukuda, Shunpei; Hashimoto, Takashi

doi:10.1111/j.1346-8138.2012.01645.x

Cited by 13 publications

(10 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Apart from its adhesion function Ln‐332 also has roles in cell migration, tissue maturation and wound repair . Since 1997, 36 anti‐Ln‐332 cases have been reported in association with an underlying malignancy . Early studies reported that 20–30% of patients had a solid cancer .…”

mentioning

confidence: 99%

Keratinocyte footprint assay discriminates antilaminin‐332 pemphigoid from all other forms of pemphigoid diseases

et al. 2019

View full text Add to dashboard Cite

Summary Background Antilaminin‐332 mucous membrane pemphigoid is a chronic severe pemphigoid disease characterized by autoantibodies to laminin‐332. At present no commercial assay is available to demonstrate antilaminin‐332 antibodies, and diagnosis relies on in‐house techniques with limited sensitivities. Objectives In order to move, keratinocytes cultured in vitro secrete laminin‐332 to attach to the culture dish. In that way, they leave behind a unique footprint trail of laminin‐332. We aimed to develop a sensitive and specific laboratory assay to determine antilaminin‐332 autoantibodies in patient serum based on binding of patient IgG to these unique footprints. Methods Normal human keratinocytes were grown on glass coverslips and incubated with patient or control serum for 1 h. The binding of IgG was then investigated by immunofluorescence. After validating the test for its ability to identify antilaminin‐332 autoantibodies it was converted into a daily available test based on binding of IgG to dried coverslips that can be stored frozen. The staining patterns of sera from patients with antilaminin‐332 pemphigoid were then compared with those of sera from patients with other autoimmune bullous diseases and normal human sera. Results IgG of all antilaminin‐332 pemphigoid sera (n = 16) bound to laminin‐332 footprints, while all normal human controls (n = 55) were negative. From the sera of patients with other diseases (n = 72) four sera tested positive. The footprint assay was also positive for sera that were negative by salt‐split skin analysis, demonstrating that it is a very sensitive technique. Conclusions The keratinocyte footprint assay is a fast and specific assay to confirm or rule out the presence of antilaminin‐332 autoantibodies. What's already known about this topic? Antilaminin‐332 mucous membrane pemphigoid is a severe form of pemphigoid, and patients may have an increased risk of malignancies. The diagnosis of antilaminin‐332 mucous membrane pemphigoid is complicated by the lack of specific commercial tests for antilaminin‐332 antibodies and can be confirmed only in specialized laboratories. Keratinocytes in culture need laminin‐332 for adhesion and migration and therefore deposit it on the bottom of the culture dish. What does this study add? The keratinocyte footprint assay detects antilaminin‐332 autoantibodies in patient serum using the native laminin‐332 produced by cultured keratinocytes. What is the translational message? The keratinocyte footprint assay is a fast and specific assay to confirm or rule out the presence of antilaminin‐332 autoantibodies.

show abstract

mentioning

confidence: 99%

Keratinocyte footprint assay discriminates antilaminin‐332 pemphigoid from all other forms of pemphigoid diseases

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The patient presented here had circulating IgG4-autoantibodies to the γ 2-chain of laminin-332-autoantibodies determined by immunoblotting analysis. Even though studies and case reports suggest an association between detection of laminin-332-autoantibodies and paraneoplastic MMP, Bernard et al could not detect a significant relationship in a multicenter retrospective study (4, 6, 7, 25). The patient's history was positive for a prostate cancer diagnosed and treated ~1 year before the onset of the first symptoms.…”

Section: Discussionmentioning

confidence: 87%

“…If MMP is suspected clinically, diagnostic testing and treatment is required without delay in order to prevent complications like irreversible scarring potentially leading to blindness, airway stenosis, esophageal, and anogenital stricture (3). Smaller studies and case reports suggest positive laminin-332 (laminin-5)-autoantibodies to be associated with a paraneoplastic manifestation of MMP (4–7).…”

Section: Introductionmentioning

confidence: 99%

Severe Refractory Paraneoplastic Mucous Membrane Pemphigoid Successfully Treated With Rituximab

Wittenberg

Worm

2019

Front. Med.

View full text Add to dashboard Cite

Mucous membrane pemphigoid (MMP) is a rare autoimmune bullous disease of the mucous membranes, which can cause irreversible scarring and is discussed to be associated with cancer, if laminin-332-autoantibodies are present. MMP with severe ocular and laryngeal involvement is difficult to treat and can be treatment-refractory to conventional immunosuppressant therapy. A 67-year-old man with a history of prostate cancer presented to our clinic with sore throat, intraoral bullae, odynophagia, dysphonia, exertional dyspnea, and erosions of the glans penis. Clinical examination confirmed a laryngo-pharyngitis with involvement of the epiglottis and bilateral symblepharon. Diagnostics comprising multiple biopsies, direct and indirect immunofluorescence, serology analysis, and immunoblotting confirmed the diagnosis of a paraneoplastic MMP by showing a subepithelial split in histology and the presence of anti-laminin-332-antibodies. Despite combined systemic treatment with prednisolone and either dapsone or azathioprine, a progress of the disease occurred leading to severe ocular and laryngeal complications. Two month after rituximab treatment, complete disease control was achieved. This case report shows a severe ocular and life threatening laryngeal involvement of therapy-refractory paraneoplastic MMP highlighting the importance of interdisciplinary management and difficulty of diagnosing MMP despite repeated diagnostic testing.

show abstract

“… 12 Cutaneous lesions are more likely to be associated with BP180 MMP, 13 although they have been described with paraneoplastic anti-laminin 5 MMP. 14 In a cohort of 35 patients, Egan et al 5 reported a positive association between antibodies to anti-laminin 5 and an underlying solid neoplasm in 29% of cases. There is some evidence that laminin 5 expression in cancer cells may play a role in cancer biology.…”

Section: Discussionmentioning

confidence: 99%

Paraneoplastic mucous membrane pemphigoid with ocular and laryngeal involvement

Lambiel¹,

Dulguerov²,

Laffitte

et al. 2017

BMJ Case Reports

View full text Add to dashboard Cite

A 73-year-old woman was treated 8 years previously for synchronous breast and uterine neoplasms. She presented with a severe sore throat, odynophagia, dysphonia, dyspnoea, ocular irritation and weight loss over the last 3 months. Physical examination revealed ulcerations in the oral cavity, posterior pharyngeal wall and supraglottic larynx, nasal crusting, bilateral conjunctivitis and three cutaneous blisters. A diagnosis of anti-laminin 5 mucous membrane pemphigoid was retained, based on skin biopsy, direct immunofluorescence and immunoprecipitation. A positron emission tomography (PET)-CT detected multiple adenopathies. Cytology revealed adenocarcinoma with an immunocytology compatible with a breast origin and this was considered as a late metastatic recurrence of her previous breast cancer. A treatment of prednisone, dapsone and hormonotherapy was introduced, but intravenous immunoglobulin and rituximab were added due to new mucosal lesions. Despite treatment, a posterior laryngeal scar and bilateral symblepharon were developed. After 3 years, the patient is still alive and reports a satisfactory quality of life.

show abstract

Anti‐laminin‐332 mucous membrane pemphigoid with autoantibodies to α3, β3 and γ2 subunits of laminin‐332 as well as to BP230 and periplakin associated with adenocarcinoma from an unknown primary site

Cited by 13 publications

References 5 publications

Keratinocyte footprint assay discriminates antilaminin‐332 pemphigoid from all other forms of pemphigoid diseases

Keratinocyte footprint assay discriminates antilaminin‐332 pemphigoid from all other forms of pemphigoid diseases

Severe Refractory Paraneoplastic Mucous Membrane Pemphigoid Successfully Treated With Rituximab

Paraneoplastic mucous membrane pemphigoid with ocular and laryngeal involvement

Contact Info

Product

Resources

About