Dermatitis herpetiformis bodies and autoantibodies to noncutaneous organs and mitochondria in dermatitis herpetiformis

Velez, Ana Maria Abreu; Yi, Hong; Girard, J; Jing, Zhe; Ramírez, Mauricio Vasco; Arias, Luis Fernando; Smoller, Bruce; Dudley, Samuel C.; Howard, Michael S.

doi:10.7241/ourd.20124.63

Cited by 4 publications

(5 citation statements)

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“…Our study results highlight a previously documented increase in expression of metallothionein, coupled with a simultaneous expression of the TIMP1; TIMP1 may thus be expressed to inhibit damaging effects of the metallothionein [19]. Matrix metalloproteinases (MMPs) are a family of extracellular matrix (ECM) degrading enzymes that are collectively capable of degrading almost all ECM components [20,21]. The extracellular activities of MMPs are regulated by tissue inhibitors of metalloproteinases (TIMPs) [20,21].…”

Section: Discussionmentioning

confidence: 79%

“…Matrix metalloproteinases (MMPs) are a family of extracellular matrix (ECM) degrading enzymes that are collectively capable of degrading almost all ECM components [20,21]. The extracellular activities of MMPs are regulated by tissue inhibitors of metalloproteinases (TIMPs) [20,21]. Both soluble and membrane-anchored metalloproteinases participate in degradation of the ECM.…”

Section: Discussionmentioning

confidence: 99%

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Tissue inhibitor of metalloproteinase 1, matrix metalloproteinase 9, αlpha-1 antitrypsin, metallothionein and urokinase type plasminogen activator receptor in skin biopsies from patients affected by autoimmune blistering diseases

Velez¹,

Naranjo²,

Ávila³

et al. 2013

Our Dermatol Online

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Introduction: Proteinases and proteinase inhibitors have been described to play a role in autoimmune skin blistering diseases. We studied skin lesional biopsies from patients affected by several autoimmune skin blistering diseases for proteinases and proteinase inhibitors. Methods: We utilized immunohistochemistry to evaluate biopsies for α-1-antitrypsin, human matrix metalloproteinase 9 (MMP9), human tissue inhibitor of metalloproteinases 1 (TIMP-1), metallothionein and urokinase type plasminogen activator receptor (uPAR). We tested 30 patients affected by endemic pemphigus, 30 controls from the endemic area, and 15 normal controls. We also tested 30 biopsies from patients with bullous pemphigoid (BP), 20 with pemphigus vulgaris (PV), 8 with pemphigus foliaceus, and 14 with dermatitis herpetiformis (DH). Results: Contrary to findings in the current literature, most autoimmune skin blistering disease biopsies were negative for uPAR and MMP9. Only some chronic patients with El Bagre-EPF were positive to MMP9 in the dermis, in proximity to telocytes. TIMP-1 and metallothionein were positive in half of the biopsies from BP patients at the basement membrane of the skin, within several skin appendices, in areas of dermal blood vessel inflammation and within dermal mesenchymal-epithelial cell junctions.Key words: endemic pemphigus foliaceus; autoimmune blistering skin diseases; matrix metalloproteinase 9; tissue inhibitor of metalloproteinases 1; urokinase type plasminogen activator receptor; α-1-antitrypsin IntroductionMultiple theories have been proposed regarding the pathophysiology of cutaneous autoimmune blistering skin diseases (ABDs). Some involve plasminogen activation, desmoglein compensation, acetylcholine receptor antibodies, and intracellular signal control of autoantibodies [1]. Moreover, human autoantibodies and the presence of complement are primary factors in producing the blisters of human autoimmune skin blistering diseases and are thought to exert their pathogenic effect via proteases [2,3]. Few studies have tested for proteases and protease inhibitors in lesional skin from patients affected by ABDs [4,5]. We decided to investigate enzymes that could be modulated by ions that have been postulated as triggers for ABDs. We also aimed to investigate enzymes that are related to xenobiotics, based on our previous findings of metals and metalloids in skin biopsies of patients with a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El-Bagre-EPF) that are exposed to significant mercury pollution [5]. Thus, we utilized immunohistochemistry (IHC) to test for anti-human-α-1-antitrypsin, anti-human matrix metalloproteinase 9 (MMP9), anti-human tissue inhibitor of metalloproteinases 1 (TIMP1), urokinase type plasminogen activator receptor (uPAR) and for metallothionein in patients affected by autoimmune skin blistering diseases.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Tissue inhibitor of metalloproteinase 1, matrix metalloproteinase 9, αlpha-1 antitrypsin, metallothionein and urokinase type plasminogen activator receptor in skin biopsies from patients affected by autoimmune blistering diseases

Velez¹,

Naranjo²,

Ávila³

et al. 2013

Our Dermatol Online

Self Cite

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“…In our experience, it is best to combine a maximum of 3 dyes simultaneously, because the human eye cannot differentiate more colors properly. [ 11 12 14 15 ] If a confocal microscope is available, each dye has specific emission and excitation peaks that can be detected using microscopic filters for those dyes.…”

Section: Discussionmentioning

confidence: 99%

“…Our DIF and IIF using multiple fluorochromes were performed as previously described. [ 14 15 ] In brief, for DIF we recommend collecting the biopsies in Michel's transport medium at room temperature, and storing at 4°C until cut. Before cutting, we recommend washing the biopsies in Michel's washing medium, and/or in PBS (pH 7.2) for 10-15 min per wash. For frozen sections, the tissue should be embedded in OCT medium and 4-5 μ thickness sections cut.…”

Section: Methodsmentioning

confidence: 99%

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Immunofluorescence patterns in selected dermatoses, including blistering skin diseases utilizing multiple fluorochromes

Velez

Calle-Isaza²,

Howard

2015

North Am J Med Sci

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Background:Autoimmune vesiculobullous disorders represent a heterogeneous group of dermatoses whose diagnosis is made based on clinical history, histologic features, and immunopathologic features. The most commonly used techniques for the diagnosis of these diseases are direct and indirect immunofluorescence (DIF and IIF), including salt-split processing. NaCl split skin is used to determine the level of blister formation, and the localization of autoantibodies relative to the split. Classically, immunofluorescence has been performed with one fluorochrome in the diagnosis of autoimmune bullous skin diseases.Aims:To compare DIF and IIF of the skin, using a single fluorochrome versus multiple fluorochromes.Materials and Methods:We studied 20 autoimmune skin disease cases using fluorescein isothiocyanate (FITC) alone, in comparison to multiple fluorochromes (with or without DNA counterstaining).Results:The use of multiple fluorochromes helped to simultaneously visualize reactivity in multiple skin areas, in contrast to using FITC alone.Conclusions:Using multiple fluorochromes allows simultaneous labeling of two or more antigens within the same cell/or tissue section, assists in colocalization of unknown antigens with known molecules, and helps in ruling out “background” staining.

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Immunohistochemistry studies in a case of dermatitis herpetiformis demonstrate complex patterns of reactivity

Velez¹,

Oliver²,

Howard³

2013

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Introduction: Dermatitis herpetiformis (DH) is an autoimmune, clinically pleomorphic, papulovesicular disorder sometimes associated with celiac disease and gluten sensitivity. DH is categorized by subepidermal vesicles and bullae on hematoxylin and eosin (H&E) staining, and with immunoglobulin A deposits present along the dermal papillary tips on direct immunofluorescence (DIF). Case Report: We describe a 50 year old female that presented with sudden onset pruritus and clinical blisters, predominantly on extensor areas of the extremities. Biopsies for H&E examination, as well as immunohistochemistry (IHC) and DIF analysis were performed. Results: H&E examination demonstrated subepidermal blistering; within the blister lumen, numerous neutrophils were present, with occasional eosinophils and lymphocytes also seen. DIF examination revealed linear deposits of IgA along the epidermal basement membrane zone, associated with other immunoglobulins and complement. IHC examination showed similar patterns of reactivity to IgA, and also to other immunoreactants. Cells positive for CD1a were present within the blisters, correlating with S-100 staining. Cells staining positive for CD8, CD45 and occasionally CD4 and Granzyme B were seen not only in the blister lumens, but also around neurovascular packages under the blisters. Finally, CD2 positive cells were found around the upper dermal blood vessels. Discussion: Focal DIF linear IgA deposition is the classic hallmark diagnostic finding in DH. However, it is possible that genetic susceptibility and environmental triggers also play a crucial role in the pathogenesis, often acting via cellular pathways exhibiting disease-associated polymorphisms. In tolerance breakthrough, the initiating antigen presenting cells likely lead to immune system cell differentiation, and activation of adaptive immunity.Key words: dermatitis herpetiformis; immunohistochemistry; autoimmunity Abbreviations and acronyms: Dermatitis herpetiformis (DH), immunohistochemistry (IHC), direct and indirect immunofluorescence (DIF and IIF), hematoxylin and eosin (H&E), basement membrane zone (BMZ).

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Dermatitis herpetiformis bodies and autoantibodies to noncutaneous organs and mitochondria in dermatitis herpetiformis

Cited by 4 publications

References 5 publications

Tissue inhibitor of metalloproteinase 1, matrix metalloproteinase 9, αlpha-1 antitrypsin, metallothionein and urokinase type plasminogen activator receptor in skin biopsies from patients affected by autoimmune blistering diseases

Tissue inhibitor of metalloproteinase 1, matrix metalloproteinase 9, αlpha-1 antitrypsin, metallothionein and urokinase type plasminogen activator receptor in skin biopsies from patients affected by autoimmune blistering diseases

Immunofluorescence patterns in selected dermatoses, including blistering skin diseases utilizing multiple fluorochromes

Immunohistochemistry studies in a case of dermatitis herpetiformis demonstrate complex patterns of reactivity

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