Studies on complement deposits in epidermolysis bullosa acquisita and bullous pemphigoid

Mooney, E.

doi:10.1001/archderm.128.1.58

Cited by 11 publications

(8 citation statements)

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“…Interestingly, EBA antibodies are more potent activators of complement than are antibodies in the sera of patients with bullous pemphigoid, a prototypic inflammatory autoimmune bullous disease (Mooney et al, 1992). The presence of complement-activating IgG autoantibodies does not correlate with the inflammatory or noninflammatory EBA clinical phenotypes (Gandi et al, 2000).…”

Section: Figurementioning

confidence: 99%

Evidence that Anti-Type VII Collagen Antibodies Are Pathogenic and Responsible for the Clinical, Histological, and Immunological Features of Epidermolysis Bullosa Acquisita

Woodley

Chang

Saadat

et al. 2005

Journal of Investigative Dermatology

111

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Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disease characterized by autoantibodies to type VII (anchoring fibril) collagen. Therefore, it is a prototypic autoimmune disease defined by a well-known autoantigen and autoantibody. In this study, we injected hairless immune competent mice with purified immunoglobulin G (IgG) fraction of serum from rabbits immunized with the non-collagenous amino-terminal domain (NC1) of human type VII collagen, the domain known to contain immunodominant epitopes. As a control, identical mice were injected with the IgG fraction of serum from non-immunized rabbits. Mice injected with immune IgG developed subepidermal skin blisters and erosions, IgG deposits at the epidermal-dermal junction of their skin, and circulating anti-NC1 antibodies in their serum-all features reminiscent of patients with EBA. Similar concentrations of control IgG purified from normal rabbits did not induce disease in the mice. These findings strongly suggest that autoantibodies that recognize human type VII collagen in EBA are pathogenic. This murine model, with features similar to the clinical, histological, and immunological features of EBA, will be useful for the fine dissection of immunopathogenic mechanisms in EBA and for the development of new therapeutic interventions.

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Section: Figurementioning

confidence: 99%

Evidence that Anti-Type VII Collagen Antibodies Are Pathogenic and Responsible for the Clinical, Histological, and Immunological Features of Epidermolysis Bullosa Acquisita

Woodley

Chang

Saadat

et al. 2005

Journal of Investigative Dermatology

111

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“…(16, 19) Separately, complement deposition is also described in the thyroid follicular basement membranes of Hashimoto’s thyroiditis and Graves disease(20) and skin of autoimmune blistering diseases such as bullous pemphigoid, epidermolysis bullosa acquisita and mucous membrane pemphigoid. (21–23) In these skin diseases, the autoantigens are involved in cell–cell or cell–matrix adhesion in the basement membrane of the skin.…”

Section: Introductionmentioning

confidence: 99%

Classical complement pathway activation in the nasal tissue of patients with chronic rhinosinusitis

Roey

Vanison

et al. 2017

Journal of Allergy and Clinical Immunology

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Background Complement plays a major role in inflammatory diseases but its involvement and mechanisms of activation in chronic rhinosinusitis (CRS) are not known. Objectives Following earlier studies discovering autoantibodies in CRS, we sought to investigate the nature, extent, and location of complement activation in nasal tissue of patients with CRS. Specifically, we were interested in whether antibody-mediated activation via the classical pathway was a major mechanism for complement activation in CRS. Methods Nasal tissue was obtained from patients with CRS and control patients. Tissue homogenates were analyzed for complement activation products (ELISA-C5b-9, C4d, activated C1 and C5a) and major complement fixing antibodies (Luminex). Tissue sections were stained for C5b-9, C4d, and laminin. Antibodies were purified using protein A/G columns from nasal polyps (NP), matching patient serum and control serum, and assayed for basement membrane binding via ELISA. Results C5b-9 was significantly increased in NP tissue compared to UT (uncinate tissue) of CRS with NP (CRSwNP) and CRS without NP (CRSsNP) (p<0.01). Similarly, C4d was increased in NP compared to UT of CRSwNP, CRSsNP and control (p<0.05). Activated C1 was also increased in NP tissue compared to UT of CRSsNP and control (p<0.05) and was correlated with C5a (p<0.01), local immunoglobulins, especially IgM (p<0.0001) and anti-dsDNA IgG (p<0.05). Immunofluorescence showed that C5b-9 and C4d deposition occurred linearly along the epithelial basement membrane. NP tissue extracts had significantly more anti-basement membrane antibodies than sera from CRSwNP and control patients (p<0.0001). Conclusion C5b-9, C4d and activated C1 were significantly increased locally in NP tissue. C5b-9 and C4d were almost universally deposited linearly along the basement membrane of NP tissue. Furthermore, activated C1 was best correlated with local immunoglobulin levels and C5a levels. Together, these data suggest that the classical pathway plays a major role in complement activation in CRS.

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“…It has been suggested, however, that epidermolysis bullosa acquisita antibodies activate C5 more readily than bullous pemphigoid antibodies. 22 Experimental techniques which may assist diagnosis being studied include use of explant skin, 23 integrin studies 24 and antibodies to heat shock protein 60. 25 It is unclear whether epidermolysis bullosa acquisita can be distinguished from bullous lupus save on the clinical criteria used for the diagnosis of lupus.…”

Section: Discussionmentioning

confidence: 99%

Epidermolysis bullosa acquisita in childhood

Varigos

Dowling

1998

Aust J Dermatology

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This case report of an 11-year-old girl describes a juvenile form of epidermolysis bullosa acquisita, an autoimmune disease of IgG antibodies to basement membrane type 7 collagen. Our case illustrates an unusually severe, acute inflammatory presentation of this condition with prominent mucosal and constitutional features requiring admission to a paediatric burns unit. The treatment consisted of supportive topical and systemic agents, prednisolone and dapsone. She responded to dapsone alone and the course of the illness was uneventful.

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Studies on complement deposits in epidermolysis bullosa acquisita and bullous pemphigoid

Cited by 11 publications

References 0 publications

Evidence that Anti-Type VII Collagen Antibodies Are Pathogenic and Responsible for the Clinical, Histological, and Immunological Features of Epidermolysis Bullosa Acquisita

Evidence that Anti-Type VII Collagen Antibodies Are Pathogenic and Responsible for the Clinical, Histological, and Immunological Features of Epidermolysis Bullosa Acquisita

Classical complement pathway activation in the nasal tissue of patients with chronic rhinosinusitis

Epidermolysis bullosa acquisita in childhood

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