Mucous membrane pemphigoid

Du, Ge-Fei; Patzelt, Sabrina; Beek, Nina van; Schmidt, Enno

doi:10.1016/j.autrev.2022.103036

Cited by 55 publications

(70 citation statements)

References 176 publications

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“…By immunoblot analysis, sera from LAD patients showed IgA reactivity against keratinocyte-derived LAD-1 in 48%-50% and IgG reactivity in 24% of cases, whereas sera from BP patients had IgG against LAD-1 in 74% and IgA in 30% of cases ( Figures 1A,B ) ( 55 , 85 , 86 ). In addition, also patients with pemphigoid gestationis and MMP revealed serum reactivity with these two proteins ( 26 , 54 , 56 , 72 ). In MMP, 16%–41% and 14% of analyzed sera contained IgG against LAD-1 and LABD97, respectively, and 37%–59% and 15% of sera exhibited IgA reactivity against LAD-1 and LABD97, respectively ( Figure 1B ) ( 75 , 87 ).…”

Section: Epitopes On Bp180mentioning

confidence: 94%

“…In other populations, like in Tehran and Israel, pemphigus is more frequent than BP ( 25 ). Annual incidences of the other BP180-related diseases MMP, pemphigoid gestationis, and linear IgA dermatosis were reported to be 1.3 and 2.0/million/year, 0.8–2.0, and 0.25–1.0, respectively ( 21 , 26 – 29 ).…”

Section: Epidemiology and Clinical Features Of Pemphigoid Diseasesmentioning

confidence: 99%

“…In total, 87%–100% of cases exhibit IgG autoantibodies against this domain ( 33 , 69 – 73 ). Reactivities for IgG and IgA with the NC16A domain were detected in 36%–53% and 0%–28% of MMP patients, respectively ( 26 , 52 , 65 , 74 – 76 ). In LAD, 8% and 4%–20% of analyzed sera exhibit anti-BP180 NC16A IgG or IgA autoantibodies, respectively ( 75 , 77 , 78 ) ( Figure 1B ).…”

Section: Epitopes On Bp180mentioning

confidence: 99%

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Type XVII collagen: Relevance of distinct epitopes, complement-independent effects, and association with neurological disorders in pemphigoid disorders

2022

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Pemphigoid diseases (PD) are autoimmune skin blistering diseases characterized by autoantibodies directed against proteins of the cutaneous basement membrane zone (BMZ). One of the major antigens is type XVII collagen (BP180), a transmembrane glycoprotein, which is targeted in four PDs: bullous pemphigoid, mucous membrane pemphigoid, linear IgA dermatosis, and pemphigoid gestationis. To date, different epitopes on BP180 have been described to be recognized by PD disease patients’ autoantibodies. Different BP180 epitopes were associated with distinct clinical phenotypes while the underlying mechanisms are not yet fully understood. So far, the main effects of anti-BP180 reactivity are mediated by Fcγ-receptors on immune cells. More precisely, the autoantibody–antigen interaction leads to activation of complement at the BMZ and infiltration of immune cells into the upper dermis and, by the release of specific enzymes and reactive oxygen species, to the degradation of BP180 and other BMZ components, finally manifesting as blisters and erosions. On the other hand, inflammatory responses independent of Fcγ-receptors have also been reported, including the release of proinflammatory cytokines and internalization and depletion of BP180. Autoantibodies against BP180 can also be found in patients with neurological diseases. The assumption that the clinical expression of PD depends on epitope specificity in addition to target antigens, autoantibody isotypes, and antibody glycosylation is supported by the observation that epitopes of PD patients differ from those of PD patients. The aim of the present review is to describe the fine specificities of anti-BP180 autoantibodies in different PDs and highlight the associated clinical differences. Furthermore, the direct effects after binding of the autoantibodies to their target are summarized.

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Section: Epitopes On Bp180mentioning

confidence: 94%

Section: Epidemiology and Clinical Features Of Pemphigoid Diseasesmentioning

confidence: 99%

Section: Epitopes On Bp180mentioning

confidence: 99%

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Type XVII collagen: Relevance of distinct epitopes, complement-independent effects, and association with neurological disorders in pemphigoid disorders

2022

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“…Mucous membrane pemphigoid (MMP) is a subepithelial/ subepidermal blistering autoimmune disease with predominant involvement of orifice-close mucosal surfaces and autoantibodies against proteins of the dermal-epidermal junction ( Figure 1M ) ( 235 ). The main target antigens are BP180 (type XVII collagen) and laminin 332 recognized in about 80 and 10–20% of patients, respectively.…”

Section: Autoimmune Skin Diseasesmentioning

confidence: 99%

Unmet Medical Needs in Chronic, Non-communicable Inflammatory Skin Diseases

et al. 2022

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An estimated 20–25% of the population is affected by chronic, non-communicable inflammatory skin diseases. Chronic skin inflammation has many causes. Among the most frequent chronic inflammatory skin diseases are atopic dermatitis, psoriasis, urticaria, lichen planus, and hidradenitis suppurativa, driven by a complex interplay of genetics and environmental factors. Autoimmunity is another important cause of chronic skin inflammation. The autoimmune response may be mainly T cell driven, such as in alopecia areata or vitiligo, or B cell driven in chronic spontaneous urticaria, pemphigus and pemphigoid diseases. Rare causes of chronic skin inflammation are autoinflammatory diseases, or rheumatic diseases, such as cutaneous lupus erythematosus or dermatomyositis. Whilst we have seen a significant improvement in diagnosis and treatment, several challenges remain. Especially for rarer causes of chronic skin inflammation, early diagnosis is often missed because of low awareness and lack of diagnostics. Systemic immunosuppression is the treatment of choice for almost all of these diseases. Adverse events due to immunosuppression, insufficient therapeutic responses and relapses remain a challenge. For atopic dermatitis and psoriasis, a broad spectrum of innovative treatments has been developed. However, treatment responses cannot be predicted so far. Hence, development of (bio)markers allowing selection of specific medications for individual patients is needed. Given the encouraging developments during the past years, we envision that many of these challenges in the diagnosis and treatment of chronic inflammatory skin diseases will be thoroughly addressed in the future.

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“…Current therapies of MMP are aimed at managing inflammation and as such only indirectly prevent progressive fibrosis. Therapeutic regimens mainly rely on the long-term use of high-dose corticosteroids in combination with potentially corticosteroidsparing agents such as azathioprine, mycophenolate mofetil, cyclophosphamide, or intravenous immunoglobulin (2,17). With the aim of identifying more effective therapy options for mucocutaneous autoimmune diseases, particularly for the severe consequences of tissue scarring, Ahadome et al previously demonstrated that aldehyde dehydrogenase family 1 (ALDH1) is implicated in ocular mucosal scarring and inflammation (18).…”

Section: Introductionmentioning

confidence: 99%

Increased Fibrosis in a Mouse Model of Anti-Laminin 332 Mucous Membrane Pemphigoid Remains Unaltered by Inhibition of Aldehyde Dehydrogenase

et al. 2022

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Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease characterized by autoantibodies against the basal membrane zone of skin and surface-close epithelia and predominant mucosal lesions. The oral cavity and conjunctivae are most frequently affected, albeit clinical manifestations can also occur on the skin. MMP-associated lesions outside the oral cavity typically lead to scarring. Mechanisms underlying scarring are largely unknown in MMP and effective treatment options are limited. Herein, we assessed the collagen architecture in tissue samples of an antibody-transfer mouse model of anti-laminin-332 MMP. In MMP mice, increased collagen fibril density was observed in skin and conjunctival lesions compared to mice injected with normal rabbit IgG. The extracellular matrix of MMP skin samples also showed altered post-translational collagen cross-linking with increased levels of both lysine- and hydroxylysine-derived collagen crosslinks supporting the fibrotic phenotype in experimental MMP compared to control animals. In addition, we evaluated a potential anti-fibrotic therapy in experimental anti-laminin-332 MMP using disulfiram, an inhibitor of the aldehyde dehydrogenase (ALDH), which has been implicated in immune-mediated mucosal scarring. In addition, disulfiram also acts as a copper chelator that was shown to block lysyl oxidase activity, an enzyme involved in formation of collagen crosslinks. Topical use of disulfiram (300 μM in 2% [w/v] methocel) did not improve ocular lesions in experimental MMP over the 12-day treatment period in disulfiram-treated mice compared to vehicle-treated mice (n=8/group). Furthermore, C57BL6/J mice (n=8/group) were treated prophylactically with 200 mg/kg p.o. disulfiram or the solvent once daily over a period of 12 days. Systemic treatment did not show any reduction in the severity of oral and ocular lesions in MMP mice, albeit some improvement in skin lesions was observed in disulfiram- vs. vehicle-treated mice (p=0.052). No reduction in fibrosis was seen, as assessed by immunohistochemistry. Whilst blocking of ALDH failed to significantly ameliorate disease activity, our data provide new insight into fibrotic processes highlighting changes in the collagenous matrix and cross-linking patterns in IgG-mediated MMP.

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Mucous membrane pemphigoid

Cited by 55 publications

References 176 publications

Type XVII collagen: Relevance of distinct epitopes, complement-independent effects, and association with neurological disorders in pemphigoid disorders

Type XVII collagen: Relevance of distinct epitopes, complement-independent effects, and association with neurological disorders in pemphigoid disorders

Unmet Medical Needs in Chronic, Non-communicable Inflammatory Skin Diseases

Increased Fibrosis in a Mouse Model of Anti-Laminin 332 Mucous Membrane Pemphigoid Remains Unaltered by Inhibition of Aldehyde Dehydrogenase

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