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Medicina Clinica Nov 2021
Topics: COVID-19; COVID-19 Vaccines; Humans; Pemphigoid, Bullous; SARS-CoV-2
PubMed: 34119340
DOI: 10.1016/j.medcli.2021.05.005 -
Frontiers in Immunology 2019Pemphigoid diseases are a subgroup of autoimmune skin diseases characterized by widespread tense blisters. Standard of care typically involves immunosuppressive... (Review)
Review
Pemphigoid diseases are a subgroup of autoimmune skin diseases characterized by widespread tense blisters. Standard of care typically involves immunosuppressive treatments, which may be insufficient and are often associated with significant adverse events. As such, a deeper understanding of the pathomechanism(s) of pemphigoid diseases is necessary in order to identify improved therapeutic approaches. A major initiator of pemphigoid diseases is the accumulation of autoantibodies against proteins at the dermal-epidermal junction (DEJ), followed by protease activation at the lesion. The contribution of proteases to pemphigoid disease pathogenesis has been investigated using a combination of and models. These studies suggest proteolytic degradation of anchoring proteins proximal to the DEJ is crucial for dermal-epidermal separation and blister formation. In addition, proteases can also augment inflammation, expose autoantigenic cryptic epitopes, and/or provoke autoantigen spreading, which are all important in pemphigoid disease pathology. The present review summarizes and critically evaluates the current understanding with respect to the role of proteases in pemphigoid diseases.
Topics: Autoantibodies; Autoantigens; Dermis; Epidermis; Humans; Pemphigoid, Bullous; Peptide Hydrolases
PubMed: 31297118
DOI: 10.3389/fimmu.2019.01454 -
Acta Dermato-venereologica Feb 2020Pemphigoid diseases are organ-specific autoimmune diseases of the skin and/or mucous membranes. They are caused by autoantibodies targeting adhesion molecules located at... (Review)
Review
Pemphigoid diseases are organ-specific autoimmune diseases of the skin and/or mucous membranes. They are caused by autoantibodies targeting adhesion molecules located at the dermal-epidermal junction. While the diagnostics of pemphigoid diseases and insights into their pathogenesis have improved significantly, the development of novel treatments that are effective and safe remains an unmet medical need. However, numerous pre-clinical studies and early clinical trials have recently been launched. This review summarizes some pathways leading to drug development in pemphigoid diseases, namely: (i) hypothesis-driven drug development; (ii) omics-based drug development; (iii) drug repurposing; (iv) screening-based drug development; and (v) drug development based on careful clinical observations. Ultimately, it is hoped that this will lead to personalized and curative treatments.
Topics: Autoantibodies; Autoimmune Diseases; Cell Adhesion Molecules; Dimethyl Fumarate; Doxycycline; Drug Development; Epidermolysis Bullosa Acquisita; Female; Forecasting; Humans; Male; Molecular Targeted Therapy; Pemphigoid, Bullous; Protein-Tyrosine Kinases; Skin Diseases, Vesiculobullous; Translational Research, Biomedical
PubMed: 32039458
DOI: 10.2340/00015555-3400 -
International Journal of Molecular... Nov 2021BP180 is a type II collagenous transmembrane protein and is best known as the major autoantigen in the blistering skin disease bullous pemphigoid (BP). The BP180 trimer... (Review)
Review
BP180 is a type II collagenous transmembrane protein and is best known as the major autoantigen in the blistering skin disease bullous pemphigoid (BP). The BP180 trimer is a central component in type I hemidesmosomes (HD), which cause the adhesion between epidermal keratinocytes and the basal lamina, but BP180 is also expressed in several non-HD locations, where its functions are poorly characterized. The immunological roles of intact and proteolytically processed BP180, relevant in BP, have been subject to intensive research, but novel functions in cell proliferation, differentiation, and aging have also recently been described. To better understand the multiple physiological functions of BP180, the focus should return to the protein itself. Here, we comprehensively review the properties of the BP180 molecule, present new data on the biochemical features of its intracellular domain, and discuss their significance with regard to BP180 folding and protein-protein interactions.
Topics: Autoantigens; Hemidesmosomes; Humans; Keratinocytes; Non-Fibrillar Collagens; Pemphigoid, Bullous; Protein Folding; Collagen Type XVII
PubMed: 34830116
DOI: 10.3390/ijms222212233 -
Journal of the American Academy of... May 2018Bullous pemphigoid is an autoimmune disease that typically presents with tense bullae and severe pruritus. However, bullae can be lacking, a subtype termed nonbullous... (Review)
Review
BACKGROUND
Bullous pemphigoid is an autoimmune disease that typically presents with tense bullae and severe pruritus. However, bullae can be lacking, a subtype termed nonbullous pemphigoid.
OBJECTIVE
To summarize the reported characteristics of nonbullous pemphigoid.
METHODS
The EMBASE and MEDLINE databases were searched using "nonbullous pemphigoid" and various synonyms. Case reports and series describing nonbullous pemphigoid were included.
RESULTS
The search identified 133 articles. After selection, 39 articles were included, presenting 132 cases. Erythematous, urticarial plaques (52.3%) and papules/nodules (20.5%) were the most reported clinical features. The mean age at presentation was 74.9 years. Histopathology was commonly nonspecific. Linear depositions of IgG and/or C3 along the basement membrane zone were found by direct immunofluorescence microscopy in 93.2%. Indirect immunofluorescence on salt-split skin was positive in 90.2%. The mean diagnostic delay was 22.6 months. A minority of patients (9.8%) developed bullae during the reported follow-up.
LIMITATIONS
Results are mainly based on case reports and small case series.
CONCLUSION
Nonbullous pemphigoid is an underdiagnosed variant of pemphigoid that most often does not evolve to bullous lesions and mimics other pruritic skin diseases. Greater awareness among physicians is needed to avoid delay in diagnosis.
Topics: Age Factors; Aged; Aged, 80 and over; Autoantigens; Biopsy, Needle; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique, Indirect; Humans; Immunoglobulin G; Immunohistochemistry; Incidence; Male; Pemphigoid, Bullous; Prognosis; Pruritus; Severity of Illness Index; Sex Factors
PubMed: 29102490
DOI: 10.1016/j.jaad.2017.10.035 -
Frontiers in Immunology 2021Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disorder in the elderly. Systemic and topical use of glucocorticoids and immunosuppressants... (Review)
Review
Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disorder in the elderly. Systemic and topical use of glucocorticoids and immunosuppressants has been shown to be effective in most patients. However, refractory BP patients are challenged to clinicians with severe clinical symptoms, resistance to treatment, and high relapse rate. How to predict and assess the refractory and severity of bullous pemphigoid is the key issue in clinical practice, and the urgent need for precision medicine in refractory patients is driving the search for biomarkers and biologics. Recently, some biomarkers, such as the level of specific autoantibodies and released cytokines, have been proposed as the potential parameters to reflect the disease severity and predict the treatment response and relapse of refractory BP. Moreover, new biologics targeting pathogenic antibodies, complement, Th2 axis, eosinophils, and Th17 axis have shown potent efficacy on refractory BP. Here, we review the literature and give an overview of emerging biomarkers and therapeutic strategies for refractory bullous pemphigoid to improve the prognosis of the patient.
Topics: Animals; Autoantibodies; Biomarkers; Cytokines; Disease Management; Disease Susceptibility; Humans; Immunoglobulin E; Immunoglobulin G; Inflammation Mediators; Leukocytes; Pemphigoid, Bullous; Prognosis; Severity of Illness Index
PubMed: 34504496
DOI: 10.3389/fimmu.2021.718073 -
Frontiers in Immunology 2020
Topics: Animals; Autoimmune Diseases; Autoimmunity; Disease Management; Disease Susceptibility; Humans; Pemphigoid, Bullous; Pemphigus
PubMed: 32793239
DOI: 10.3389/fimmu.2020.01614 -
Orphanet Journal of Rare Diseases Sep 2014Gestational pemphigoid (pemphigoid gestationis, PG) is a rare autoimmune skin disorder occurring characteristically during pregnancy. Autoantibodies against placental... (Review)
Review
Gestational pemphigoid (pemphigoid gestationis, PG) is a rare autoimmune skin disorder occurring characteristically during pregnancy. Autoantibodies against placental BP180 (also known as BPAG2 or collagen XVII) cause damage to the skin basement membrane, resulting in severe itching and blistering rash over the body and the extremities. The diagnosis of PG is confirmed by immunofluorescence analysis of a skin biopsy, while serum levels of pemphigoid antigen BP180 antibody can be used to assess disease activity. PG with mild symptoms can be treated with topical corticosteroids, while oral corticosteroids are the mainstay in treatment of severe PG. PG usually flares up at the time of delivery, and resolves spontaneously shortly after. However, relapses in subsequent pregnancies are common. As PG has been linked to the risk of prematurity and fetal growth restriction, prenatal monitoring jointly by a dermatologist and an obstetrician is recommended. Mothers should also be informed of the potential risk of re-activation of the disease in subsequent pregnancies and during hormonal contraception.
Topics: Autoantigens; Biopsy; Diagnosis, Differential; Female; Fluorescent Antibody Technique, Direct; Humans; Infant, Newborn; Non-Fibrillar Collagens; Pemphigoid, Bullous; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prognosis; Collagen Type XVII
PubMed: 25178359
DOI: 10.1186/s13023-014-0136-2 -
Frontiers in Immunology 2023Autoimmune blistering diseases such as bullous pemphigoid (BP) and pemphigus vulgaris (PV) are complex, multifactorial, and polygenic diseases, whose exact pathogenesis... (Review)
Review
Autoimmune blistering diseases such as bullous pemphigoid (BP) and pemphigus vulgaris (PV) are complex, multifactorial, and polygenic diseases, whose exact pathogenesis is difficult to pinpoint. Research aimed at elucidating the associated epidemiologic risk factors of these two diseases has been hampered by their rare disease status. Further, a lack of centralization and standardization of available data makes the practical application of this information challenging. In order to collate and clarify the available literature we comprehensively reviewed 61 PV articles from 37 different countries and 35 BP articles from 16 different countries addressing a range of disease relevant clinical parameters including age of onset, sex, incidence, prevalence, and HLA allele association. The reported incidence of PV ranged from 0.098 to 5 patients per 100,000 people, while BP ranged from 0.21 to 7.63 patients per 100,000. Prevalence of PV ranged from 0.38 to 30 per 100,000 people and BP ranged from 1.46 to 47.99 per 100,000. The mean age of onset in patients ranged from 36.5 to 71 years for PV and 64 to 82.6 years for BP. Female-to-male ratios ranged from 0.46 to 4.4 in PV and 1.01 to 5.1 in BP. Our analysis provides support for the reported linkage disequilibrium of HLA DRB1*0402 (an allele previously shown to be associated with PV) and DQB1*0302 alleles in Europe, North America, and South America. Our data also highlight that HLA DQB1*0503 (also known to be associated with PV) appears in linkage disequilibrium with DRB1*1404 and DRB1*1401, mainly in Europe, the Middle East, and Asian countries. The HLA DRB1*0804 allele was only associated with PV in patients of Brazilian and Egyptian descent. Only two HLA alleles were reported as associated with BP more than twice in our review, DQB1*0301 and DQA1*0505. Collectively, our findings provide detailed insights into the variation of disease parameters relevant to PV and BP that can be expected to inform future work aimed at unraveling the complex pathogenesis of these conditions across the globe.
Topics: Humans; Male; Female; Adult; Middle Aged; Aged; Pemphigus; HLA-DRB1 Chains; Pemphigoid, Bullous; Genetic Predisposition to Disease; Haplotypes; Epidemiologic Factors; Autoimmune Diseases; Brazil
PubMed: 37180132
DOI: 10.3389/fimmu.2023.1159351 -
Frontiers in Immunology 2019Bullous pemphigoid (BP) is an organ-specific autoantibody-mediated blistering skin disease that mainly affects the elderly. Typical clinical features include the... (Review)
Review
Bullous pemphigoid (BP) is an organ-specific autoantibody-mediated blistering skin disease that mainly affects the elderly. Typical clinical features include the widespread blisters, often preceded by and/or associated with itchy urticarial or eczema-like lesions. BP patients have circulating autoantibodies against BP180 and/or the plakin family protein BP230 both of which are components of hemidesmosomes in basal keratinocytes. Most BP autoantibodies particularly target the epitopes within the non-collagenous NC16A domain of BP180. Clinical findings and murine models of BP have provided evidence of a pathogenic role of anti-NC16A autoantibodies. However, it is largely unknown what triggers the breakage of immunotolerance against BP180 in elderly individuals. The incidence of BP has been increased over the past two decades in several countries. Aside from aging populations, the factors behind this phenomenon are still not fully understood. Neurodegenerative diseases such as multiple sclerosis, Parkinson's disease, and certain dementias are independent risk factors for BP. Recently several case reports have described BP in patients with diabetes mellitus (DM) patients who have been treated with dipeptidyl peptidase-4 inhibitors (DPP-4i or gliptins), which are a widely used class of anti-DM drugs. The association between the use of DPP-4is, particularly vildagliptin, and BP risk has been confirmed by several epidemiological studies. Evidence suggests that cases of gliptin-associated BP in Japan display certain features that set them apart from cases of "regular" BP. These include a "non-inflammatory" phenotype, targeting by antibodies of different immunodominant BP180 epitopes, and a specific association with the human leukocyte antigen (HLA) types. However, recent studies in European populations have found no major differences between the clinical and immunological characteristics of gliptin-associated BP and "regular" BP. The DPP-4 protein (also known as CD26) is ubiquitously expressed and has multiple functions in various cell types. The different effects of the inhibition of DPP-4/CD26 activity include, for example, tissue modeling and regulation of inflammatory cells such as T lymphocytes. Although the pathomechanism of gliptin-associated BP is currently largely unknown, investigation of the unique effect of gliptins in the induction of BP may provide a novel route to better understanding of how immunotolerance against BP180 breaks down in BP.
Topics: Animals; Diabetes Mellitus; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Humans; Hypoglycemic Agents; Japan; Pemphigoid, Bullous; Vildagliptin
PubMed: 31275298
DOI: 10.3389/fimmu.2019.01238