Congenital Epidermolysis Bullosa Acquisita

Abrams, Melissa; Smidt, Aimee C.; Benjamin, Latanya; Chen, Mei; Woodley, David T.; Mancini, Anthony J.

doi:10.1001/archdermatol.2010.317

Cited by 49 publications

(13 citation statements)

References 29 publications

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“…However, by 3 months, IgG antidesmoglein levels in the neonate are within normal limits [113]. Transient neonatal autoimmune diseases have also been reported for myasthenia gravis and antiphospholipid syndrome, and recently, a case was reported of a newborn with transient epidermolysis bullosa acquisita, a chronic, autoimmune bullous dermatosis due to the passive transfer of maternal autoantibodies against the noncollagenous terminus of the α chain of type VII collagen [114–116]. …”

Section: Placental Transfer In Mothers With Autoimmune Diseasesmentioning

confidence: 99%

IgG Placental Transfer in Healthy and Pathological Pregnancies

Palmeira

Quinello

Silveira-Lessa

et al. 2012

Clinical and Developmental Immunology

776

746

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Placental transfer of maternal IgG antibodies to the fetus is an important mechanism that provides protection to the infant while his/her humoral response is inefficient. IgG is the only antibody class that significantly crosses the human placenta. This crossing is mediated by FcRn expressed on syncytiotrophoblast cells. There is evidence that IgG transfer depends on the following: (i) maternal levels of total IgG and specific antibodies, (ii) gestational age, (iii) placental integrity, (iv) IgG subclass, and (v) nature of antigen, being more intense for thymus-dependent ones. These features represent the basis for maternal immunization strategies aimed at protecting newborns against neonatal and infantile infectious diseases. In some situations, such as mothers with primary immunodeficiencies, exogenous IgG acquired by intravenous immunoglobulin therapy crosses the placenta in similar patterns to endogenous immunoglobulins and may also protect the offspring from infections in early life. Inversely, harmful autoantibodies may cross the placenta and cause transitory autoimmune disease in the neonate.

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Section: Placental Transfer In Mothers With Autoimmune Diseasesmentioning

confidence: 99%

IgG Placental Transfer in Healthy and Pathological Pregnancies

Palmeira

Quinello

Silveira-Lessa

et al. 2012

Clinical and Developmental Immunology

776

746

View full text Add to dashboard Cite

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“…Based on the assumption of disease induction by placental autoantibody transfer, supportive treatment was initiated. This led to cession of new blister formation within 10 days and healing of all erosions within 2 months [11]. …”

Section: Congenital Ebamentioning

confidence: 99%

Clinical Presentation, Pathogenesis, Diagnosis, and Treatment of Epidermolysis Bullosa Acquisita

Ludwig

2013

ISRN Dermatology

124

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Epidermolysis bullosa acquisita (EBA) is a chronic mucocutaneous autoimmune skin blistering disease. The pathogenic relevance of autoantibodies targeting type VII collagen (COL7) has been well-documented. Therefore, EBA is a prototypical autoimmune disease with a well-characterized pathogenic relevance of autoantibody binding to the target antigen. EBA is a rare disease with an incidence of 0.2 new cases per million and per year. The current treatment of EBA relies on general immunosuppressive therapy, which does not lead to remission in all cases. Therefore, there is a high, so far unmet medical need for the development of novel therapeutic options. During the last 10 years, several novel in vitro and in vivo models of EBA have been established. These models demonstrated a critical role of the genetic background, T cells, and cytokines for mediating the loss of tolerance towards COL7. Neutrophils, complement activation, Fc gamma receptor engagement, cytokines, several molecules involved in cell signaling, release of reactive oxygen species, and matrix metalloproteinases are crucial for autoantibody-induced tissue injury in EBA. Based on this growing understanding of the diseases' pathogenesis, several potential novel therapeutic targets have emerged. In this review, the clinical presentation, pathogenesis, diagnosis, and current treatment options for EBA are discussed in detail.

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“…Accumulating clinical and experimental evidence demonstrates that collagen VII-specific IgG autoantibodies are pathogenic. Transient skin blistering was reported in a newborn from a mother with EBA showing the transplacental transfer of pathogenic autoantibodies [8]. IgG autoantibodies from EBA patients induced dermal-epidermal separation in frozen sections of normal human skin when co-incubated with granulocytes from healthy donors [9].…”

Section: Introductionmentioning

confidence: 99%

Prevalence of collagen VII-specific autoantibodies in patients with autoimmune and inflammatory diseases

et al. 2012

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BackgroundAutoimmunity to collagen VII is typically associated with the skin blistering disease epidermolysis bullosa acquisita (EBA), but also occurs occasionally in patients with systemic lupus erythematosus or inflammatory bowel disease. The aim of our present study was to develop an accurate immunoassay for assessing the presence of autoantibodies against collagen VII in large cohorts of patients and healthy donors.MethodsBased on in silico antigenic analysis and previous wetlab epitope mapping data, we designed a chimeric collagen VII construct containing all collagen VII epitopes with higher antigenicity. ELISA was performed with sera from patients with EBA (n = 50), Crohn's disease (CD, n = 50), ulcerative colitis (UC, n = 50), bullous pemphigoid (BP, n = 76), and pemphigus vulgaris (PV, n = 42) and healthy donors (n = 245).ResultsBy ELISA, the receiver operating characteristics analysis yielded an area under the curve of 0.98 (95% CI: 0.9638-1.005), allowing to set the cut-off at 0.32 OD at a calculated specificity of 98% and a sensitivity of 94%. Running the optimized test showed that serum IgG autoantibodies from 47 EBA (94%; 95% CI: 87.41%-100%), 2 CD (4%; 95% CI: 0%-9.43%), 8 UC (16%; 95% CI: 5.8%-26%), 2 BP (2.63%; 95% CI: 0%-6.23%), and 4 PV (9.52%; 95% CI: 0%-18.4%) patients as well as from 4 (1.63%; 95% CI: 0%-3.21%) healthy donors reacted with the chimeric protein. Further analysis revealed that in 34%, 37%, 16% and 100% of sera autoantibodies of IgG1, IgG2, IgG3, and IgG4 isotype, respectively, recognized the recombinant autoantigen.ConclusionsUsing a chimeric protein, we developed a new sensitive and specific ELISA to detect collagen specific antibodies. Our results show a low prevalence of collagen VII-specific autoantibodies in inflammatory bowel disease, pemphigus and bullous pemphigoid. Furthermore, we show that the autoimmune response against collagen VII is dominated by IgG4 autoantibodies. The new immunoassay should prove a useful tool for clinical and translational research and should improve the routine diagnosis and disease monitoring in diseases associated with collagen VII-specific autoimmunity.

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Congenital Epidermolysis Bullosa Acquisita

Cited by 49 publications

References 29 publications

IgG Placental Transfer in Healthy and Pathological Pregnancies

IgG Placental Transfer in Healthy and Pathological Pregnancies

Clinical Presentation, Pathogenesis, Diagnosis, and Treatment of Epidermolysis Bullosa Acquisita

Prevalence of collagen VII-specific autoantibodies in patients with autoimmune and inflammatory diseases

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