Autoimmune Bullous Disease in Childhood.
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ABSTRACT:
SUBMITTER: Salman A
PROVIDER: S-EPMC5527737 | biostudies-other | 2017 Jul-Aug
REPOSITORIES: biostudies-other
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Project description:Eosinophils are typically associated with unique inflammatory settings, including allergic inflammation and helminth infections. However, new information suggests that eosinophils contribute more broadly to inflammatory responses and participate in local immune regulation and the tissue remodeling/repair events linked with a variety of diseases. Eosinophilic infiltration has long been a histologic hallmark of bullous pemphigoid (BP), a subepidermal autoimmune blistering disease characterized by autoantibodies directed against basement membrane protein BP180. However, the exact role of eosinophils in disease pathogenesis remains largely unknown. We show here that eosinophils are necessary for IgE autoantibody-mediated BP blister formation in a humanized IgE receptor mouse model of BP. Disease severity is IgE dose dependent and correlates with the degree of eosinophil infiltration in the skin. Furthermore, IgE autoantibodies fail to induce BP in eosinophil-deficient mice, confirming that eosinophils are required for IgE-mediated tissue injury. Thus, eosinophils provide the cellular link between IgE autoantibodies and skin blistering in this murine model of BP. These findings suggest a role for eosinophils in autoimmune disease and have important implications for the treatment of BP and other antibody-mediated inflammatory and autoimmune diseases.
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Project description:Bullous pemphigoid (BP) is a subepidermal skin blistering disease characterized immunohistologically by dermal-epidermal junction (DEJ) separation, an inflammatory cell infiltrate in the upper dermis, and autoantibodies targeted toward the hemidesmosomal proteins BP230 and BP180. Development of an IgG passive transfer mouse model of BP that reproduces these key features of human BP has demonstrated that subepidermal blistering is initiated by anti-BP180 antibodies and mediated by complement activation, mast cell degranulation, neutrophil infiltration, and proteinase secretion. This model is not compatible with study of human pathogenic antibodies, as the human and murine antigenic epitopes are not cross-reactive. The development of two novel humanized mouse models for the first time has enabled study of disease mechanisms caused by BP autoantibodies, and presents an ideal in vivo system to test novel therapeutic strategies for disease management.
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Project description:MicroRNAs (miRNAs) are small endogenous, non-coding RNAs that control genes at post-transcriptional level. They are essential for development and tissue differentiation, and altered miRNA expression patterns are linked to the pathogenesis of inflammation and cancer. There is evidence that miRNA expression is genetically controlled similar to the transcription of protein-coding genes and previous studies identified quantitative trait loci (QTL) for miRNA expression in the liver. So far, little attention has been paid to miRNA expression in the skin. Moreover, there is no data on epistatic control of miRNA expression. In this study, we statistically linked cutaneous miRNA expression patterns to SNP (single nucleotide polymorphism) markers in an advanced murine intercross line (AIL) of three strains (BxD2, NZM and MRL) that are known to be prone to develop autoimmune diseases as well as the wild-derived strain CAST/EiJ. In particular, we screened 100 murine samples for 609 different miRNAs and identified 42 eQTL controlling the expression of 38 cutaneous miRNAs. As a result, we identified two chromosomal hot-spots on chromosome 2 and 8 that control the expression of multiple miRNAs. Moreover, for eight miRNAs, an interacting effect of pairs of SNP was observed. Combining the constraints on genes from the statistical interaction of their loci and further using curated protein interaction networks narrowed down the number of candidate genes controlling miRNAs to a set of several genes. Among the resulting interaction pairs were the genes COMMD3 and COPS5 found to regulate the expression of miR-501-5p. Independently, a network analysis based on co-expression of miRNAs was performed using WGCNA (weighted gene co-expression analysis) to identify clusters (modules) of co-expressed miRNAs. One of these modules significantly correlated with the onset and severity of epidermolysis bullosa acquisita, a cutaneous autoimmune skin blistering disease induced by autoantibodies to type VII collagen. The key miRNAs identified from this analysis were miR-379 and miR-223.This work shows strong evidence for a genetic control of cutaneous miRNA expression. 100 murine skin samples
2014-12-18 | E-GEOD-64276 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are small endogenous, non-coding RNAs that control genes at post-transcriptional level. They are essential for development and tissue differentiation, and altered miRNA expression patterns are linked to the pathogenesis of inflammation and cancer. There is evidence that miRNA expression is genetically controlled similar to the transcription of protein-coding genes and previous studies identified quantitative trait loci (QTL) for miRNA expression in the liver. So far, little attention has been paid to miRNA expression in the skin. Moreover, there is no data on epistatic control of miRNA expression. In this study, we statistically linked cutaneous miRNA expression patterns to SNP (single nucleotide polymorphism) markers in an advanced murine intercross line (AIL) of three strains (BxD2, NZM and MRL) that are known to be prone to develop autoimmune diseases as well as the wild-derived strain CAST/EiJ. In particular, we screened 100 murine samples for 609 different miRNAs and identified 42 eQTL controlling the expression of 38 cutaneous miRNAs. As a result, we identified two chromosomal hot-spots on chromosome 2 and 8 that control the expression of multiple miRNAs. Moreover, for eight miRNAs, an interacting effect of pairs of SNP was observed. Combining the constraints on genes from the statistical interaction of their loci and further using curated protein interaction networks narrowed down the number of candidate genes controlling miRNAs to a set of several genes. Among the resulting interaction pairs were the genes COMMD3 and COPS5 found to regulate the expression of miR-501-5p. Independently, a network analysis based on co-expression of miRNAs was performed using WGCNA (weighted gene co-expression analysis) to identify clusters (modules) of co-expressed miRNAs. One of these modules significantly correlated with the onset and severity of epidermolysis bullosa acquisita, a cutaneous autoimmune skin blistering disease induced by autoantibodies to type VII collagen. The key miRNAs identified from this analysis were miR-379 and miR-223.This work shows strong evidence for a genetic control of cutaneous miRNA expression.
2014-12-18 | GSE64276 | GEO
Project description:BackgroundAutoimmune bullous diseases (ABDs) are a rare but significant group of dermatoses that pose great challenges to the treating dermatologist. ABDs are characterized by the presence of tissue-bound and circulating autoantibodies directed against disease-specific target antigens of the skin. Most epidemiological studies have focused on a single ABD. More than that, there are few data about the incidence and prevalence of autoimmune blistering diseases in Romania.MethodsIn this study, between 2015 and 2019, we retrospectively investigated a total of 225 patients with autoimmune bullous diseases from the northeastern region of Romania. The diagnosis was based on the clinical and histo- and immunohistological findings.ResultsPemphigus was the most frequently encountered ABD, with an incidence of 8.16/1,000,000 inhabitants, representing 58.7% (132 cases), followed by 24% cases of bullous pemphigoid (54 cases), 15.4% of patients were diagnosed with dermatitis herpetiformis (37 cases), and 0.9% other subepidermal autoimmune bullous dermatoses. The average age of onset of pemphigus vulgaris was 59.4 years, the majority of patients being male, while the average age of patients diagnosed with bullous pemphigoid was 73.8 years, the majority being female.ConclusionsPemphigus vulgaris is the most frequently encountered ABDs in the northeast of Romania, with a higher incidence than in Western European countries, and this may be due to specific peculiarities of the geographical area, as well as to a genetic susceptibility of the population in this region.
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Project description:Autoimmune bullous dermatoses (AIBD) include a series of typical organ-specific autoimmune diseases characterized by extensive mucocutaneous blisters. It is generally accepted to be caused by pathological autoantibodies that directly target specific adhesion components of the skin or the adjacent mucous membranes. Both innate and adaptive immune systems are critically involved in the misguided immune response against self-antigens. Recent studies have indicated that the dysfunction of regulatory T cells, regulatory B cells, and complement regulatory proteins that play essential roles in maintaining a healthy immune environment is also closely related to immune disorders in AIBD. It is important to summarize these studies, elucidate the changes in these regulatory immune cells and molecules for the pathogenesis of AIBD, and reveal the mechanisms by which they lose their ability to regulate immune disorders. In this review, we highlight the role of regulatory immune cells and molecules in the pathogenesis of pemphigus vulgaris and bullous pemphigoid, the two most representative forms of AIBD, and indicate issues that should be addressed in future investigations.
| S-EPMC6688483 | biostudies-literature
Project description:Autoimmune bullous dermatoses are a heterogeneous group of diseases with autoantibodies against structural skin proteins. Although the occurrence of autoimmune bullous dermatoses during pregnancy is low, this topic deserves attention, since the immunological and hormonal alterations that occur during this period can produce alterations during the expected course of these dermatoses. The authors review the several aspects of autoimmune bullous dermatoses that affect pregnant women, including the therapeutic approach during pregnancy and breastfeeding. Gestational pemphigoid, a pregnancy-specific bullous disease, was not studied in this review.
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Project description:ObjectivesAutoimmune bullous diseases vary in their clinico-epidemiological features and burden across populations. Data about these diseases was lacking in Sudan. We aimed to describe the epidemiological profile and to estimate the burden of autoimmune bullous diseases in Sudan.MethodsThis was a retrospective cross-sectional study conducted at Khartoum Dermatological and Venereal Diseases Teaching Hospital. We used routinely collected health care data, and included all patients with an autoimmune bullous disease who presented to the hospital between 2001 and 2016.ResultsOut of the 4736 patients who were admitted to the hospital during the study period, 923 (19.5%) had an autoimmune bullous disease. The average rate of patients at the hospital was 57.7 per year representing 1.3 per 100,000 population per year. After exclusion of patients where the final diagnosis was missing, 585 were included in the further analysis. Pemphigus vulgaris was the most common disease (50.9%), followed by bullous pemphigoid (28.2%), linear IgA disease/chronic bullous disease of childhood (8.4%), and pemphigus foliaceous (8.2%). Pemphigoid gestationis and IgA pemphigus constituted 1.4% and 1.2% of the cohort, respectively. Paraneoplastic pemphigus, mucous membrane pemphigoid, lichen planus pemphigoidis, bullous systemic lupus erythematosus, and dermatitis herpetiformis were rare. None of the patients had epidermolysis bullosa acquisita.ConclusionsThe clinico-epidemiological characteristics vary among the types of autoimmune bullous diseases. Females were more predominant in most of them. Sudanese patients tended in general to present at a younger age than other populations. The pool of Sudanese patients with autoimmune bullous diseases is large which requires investigation for the local risk factors and presents a field for future trials.
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Project description:Autoimmune thyroid disease (ATD) is the most frequent cause of acquired thyroid dysfunction, most commonly presenting either as Hashimoto's thyroiditis or Graves' Disease. Hashimoto's thyroiditis is characterized by the presence of thyroid-specific autoantibodies, more commonly anti-thyroperoxidase antibodies in the serum and the typical inhomogeneous echostructure of the thyroid on a thyroid ultrasound examination. Hashimoto's thyroiditis can for a long time be accompanied by normal thyroid function and hypothyroidism can only progressively be established. Graves' disease is much less frequent in childhood and adolescence and presents with overt hyperthyroidism. After the onset of puberty, ATD affects females with a higher incidence than males, while during the prepubertal period there is not such a clear preponderance of affected females. ATD can occur either isolated or in the context of other autoimmune disorders, such as type 1 Diabetes mellitus (T1D), celiac disease, alopecia areata, vitiligo, etc. Especially at the pediatric age, a higher incidence of ATD is also observed in the context of specific genetic syndromes, such as trisomy 21 (Down syndrome), Klinefelter syndrome, Turner syndrome, or 22q11.2 deletion syndrome. Nevertheless, although thyroid dysfunction may also be observed in other genetic syndromes, such as Prader-Willi or Williams syndrome, the thyroid dysfunction in these syndromes is not the result of thyroid autoimmunity. Interestingly, there is emerging evidence supporting a possible link between autoimmunity and RASopathies. In this review article the incidence, as well as the clinical manifestation and accompanied pathologies of ATD in specific genetic syndromes will be presented and regular follow-up for the early identification of the disorder will be proposed.
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Project description:Pemphigus and bullous pemphigoid are autoantibody-mediated blistering skin diseases. In pemphigus, keratinocytes in epidermis and mucous membranes lose cell-cell adhesion, and in pemphigoid, the basal keratinocytes lose adhesion to the basement membrane. Pemphigus lesions are mediated directly by the autoantibodies, whereas the autoantibodies in pemphigoid fix complement and mediate inflammation. In both diseases, the autoantigens have been cloned and characterized; pemphigus antigens are desmogleins (cell adhesion molecules in desmosomes), and pemphigoid antigens are found in hemidesmosomes (which mediate adhesion to the basement membrane). This knowledge has enabled diagnostic testing for these diseases by enzyme-linked immunosorbent assays and dissection of various pathophysiological mechanisms, including direct inhibition of cell adhesion, antibody-induced internalization of antigen, and cell signaling. Understanding these mechanisms of disease has led to rational targeted therapeutic strategies.
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