scholarly journals Tissue Factor in Dermatitis Herpetiformis and Bullous Pemphigoid: Link between Immune and Coagulation System in Subepidermal Autoimmune Bullous Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Agnieszka Zebrowska ◽  
Malgorzata Wagrowska-Danilewicz ◽  
Marian Danilewicz ◽  
Joanna Wieczfinska ◽  
Ewa Pniewska ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Bullous Pemphigoid ◽  
Skin Diseases ◽  
Dermatitis Herpetiformis ◽  
Plasma Concentrations ◽  
Coagulation System ◽  
Variable Expression ◽  
Autoimmune Bullous Diseases ◽  
Skin Biopsies ◽  
Perilesional Skin

Dermatitis herpetiformis (DH) and bullous pemphigoid (BP) are skin diseases associated with eosinophilic and neutrophilic infiltrations. Although chemokines are critical for the selective accumulation and activation of various leukocyte subsets in the inflammatory process, there are few findings concerning inflammatory cells and production of coagulation factors in blistering diseases. Skin biopsies were taken from 14 patients with DH, 27 with BP, and 20 control subjects. The localization and expression of tissue factor (TF) in skin lesions and perilesional skin were studied by immunohistochemistry and confirmed by Western Blot. Moreover the plasma concentrations of TF were measured by immunoassays. D dimers, fibrinogen, and selected coagulation parameters were measured by routine methods. Expression of TF in the epidermis and in inflammatory influxed cells in dermis was detected in skin biopsies from BP patients. Examined TF expression was detected in perilesional skin of all BP patients too. The expression of TF was not observed in biopsies from healthy people and DH patients. The findings of the study show an increased expression of tissue factor in the lesional and perilesional skin of patients with bullous pemphigoid. The difference in chemokine pattern expression and variations in the cellular infiltration in BP and DH cause variable expression of TF.

scholarly journals Mediators of Mast Cells in Bullous Pemphigoid and Dermatitis Herpetiformis

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Agnieszka Zebrowska ◽  
Malgorzata Wagrowska-Danilewicz ◽  
Marian Danilewicz ◽  
Olga Stasikowska-Kanicka ◽  
Lilianna Kulczycka-Siennicka ◽  
...  
Keyword(s):  
Mast Cells ◽  
Bullous Pemphigoid ◽  
Skin Diseases ◽  
Dermatitis Herpetiformis ◽  
Skin Lesions ◽  
Autoimmune Blistering Disease ◽  
Mmp9 Expression ◽  
Skin Biopsies ◽  
Cell Expression ◽  
Perilesional Skin

Bullous pemphigoid (BP) and dermatitis herpetiformis (DH) are skin diseases associated with inflammation. However, few findings exist concerning the role of mast cells in autoimmune blistering disease. Skin biopsies were taken from 27 BP and 14 DH patients, as well as 20 healthy individuals. Immunohistochemistry was used to identify the localization and mast cell expression of TNFα and MMP9 in skin lesions and perilesional skin. The serum concentrations of TNFα, MMP9, chymase, tryptase, PAF, and IL-4 were measured by immunoassay. TNFα and MMP9 expression in the epidermis and in inflammatory influxed cells in the dermis was detected in skin biopsies from patients. Although these mediators were found to be expressed in the perilesional skin of all patients, the level was much lower than that in lesional skin. Increased serum PAF levels were observed in BP patients. Mast cells may play an essential role in activating inflammation, which ultimately contributes to the tissue damage observed in BP and DH. Our findings suggest that differences in the pattern of cytokine expression directly contribute to variations in cellular infiltration in DH and BP.

scholarly journals IL-17 Expression in Dermatitis Herpetiformis and Bullous Pemphigoid

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Agnieszka Zebrowska ◽  
Malgorzata Wagrowska-Danilewicz ◽  
Marian Danilewicz ◽  
Olga Stasikowska-Kanicka ◽  
Anna Cynkier ◽  
...  
Keyword(s):  
Bullous Pemphigoid ◽  
Healthy Subjects ◽  
Inflammatory Process ◽  
Essential Role ◽  
Skin Diseases ◽  
Dermatitis Herpetiformis ◽  
Control Group ◽  
Bullous Diseases ◽  
Skin Biopsies ◽  
Perilesional Skin

Dermatitis herpetiformis (DH) and bullous pemphigoid (BP) are skin diseases associated with eosinophilic and neutrophilic infiltrations. Although cytokines are critical for the inflammatory process, there are single findings concerning concentration of IL-17 in bullous diseases. The goal of this study was to assess IL-17 expression in DH and BP patients. Skin biopsies were taken from 10 DH, 14 BP patients and from 10 healthy subjects. The localization and expression of IL-17 was studied by immunohistochemistry and the serum concentration was measured by immunoassays. Expression of IL-17 in the epidermis and in influxed cells in dermis was detected in skin biopsies. Expression of IL-17 was statistically higher in epidermis and infiltration cells in specimens from BP than from DH patients. Examined interleukin expression was detected in perilesional skin of all patients but it was much lower than in lesional skin. The expression of IL-17 was not observed in biopsies from healthy people. Serum level of IL-17 was statistically higher in BP and DH groups as compared to control group. Our results provide the evidence that IL-17 may play an essential role in activating and recruiting eosinophils and neutrophils, which ultimately contribute to the tissue damage in DH and BP.

The Role of Apoptosis in the Pathogenesis of Dermatitis Herpetiformis

2005 ◽  
Vol 18 (4) ◽  
pp. 691-699 ◽  
Author(s):  
M. Caproni ◽  
D. Torchia ◽  
E. Antiga ◽  
D. Degl'Innocenti ◽  
E. Barletta ◽  
...  
Keyword(s):  
Fas Ligand ◽  
Skin Diseases ◽  
Dermatitis Herpetiformis ◽  
Basal Layer ◽  
Immunohistochemical Analysis ◽  
Skin Lesions ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Cutaneous Lesions ◽  
Malignant Skin ◽  
Perilesional Skin

Apoptosis is a form of cell death that is claimed to be involved in a number of chronic inflammatory and malignant skin diseases. The aim of this study was to investigate whether apoptosis may contribute to the pathogenesis of epidermal changes in dermatitis herpetiformis (DH) and, in particular, whether certain apoptosis-related markers such as Bax, Bcl-2, Fas and Fas ligand (FasL) take part in this process. For the detection of apoptotic nuclei, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling technique (TUNEL) was employed on cryostat sections. Skin lesions from six and perilesional skin from four DH patients were stained with monoclonal antibodies to Bax, Bcl-2, Fas and FasL. The same evaluation was also performed on three patients affected by bullous pemphigoid (BP) and in two healthy donors. Using TUNEL technique, a remarkable increase in the apoptotic rate within the epidermal compartment was observed in DH and BP patients in comparison with normal controls. In our immunohistochemical analysis, Bax/Bcl-2 ratio was almost the same in the epidermis of perilesional/lesional DH, BP and healthy skin specimens. In DH and BP specimens both Bax and Bcl-2 proteins were increased in the dermal perivascular compartment. Fas showed a prevalently epidermal staining, both in DH and BP lesions, while FasL was distributed in perivascular and subjunctional dermis; some FasL+ cells infiltrated the DEJ and the basal layer of epidermis. This study allowed us to highlight conspicuous apoptotic phenomena in basal and suprabasal keratinocytes within lesional and perilesional skin of DH. We conclude that in DH, as well as in BP, apoptosis plays a role in the pathogenesis of cutaneous lesions in concert with other pathogenetic mechanisms.

scholarly journals Correlation of Circulating Microparticles with Coagulation and Fibrinolysis Is Healthy Individuals

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4975-4975
Author(s):  
Venencia Albert ◽  
Arulselvi Subramanian ◽  
Hara Prasad Pati
Keyword(s):  
Cell Surface ◽  
Tissue Factor ◽  
Thrombin Generation ◽  
Plasma Concentrations ◽  
Annexin V ◽  
Coagulation System ◽  
Low Grade ◽  
Healthy Individuals ◽  
Circulating Microparticles ◽  
The Impact

Abstract Introduction Microparticles (MPs) are small membrane blebs that are released in response to cellular activation or apoptosis from the cell surface by proteolytic cleavage of the cytoskeleton. Previous studies have reported low levels of naturally produced cell-derived microparticle in healthy individuals. This study was conducted to assess whether circulating microparticles induce thrombin generation leading to low grade activation of the coagulation system in healthy individuals. Materials & Methods Flow cytometry analysis of three phenotypes of Platelet derived (PMP), Endothelial derived (EMP) and TF bearing (TFMP) microparticles was done in in the 20 healthy individuals. Triple gating strategy (i) particle size(<0.5µm) (ii) expression of cell surface markers (PMP, CD42a+; EMP, CD62E+; TF bearing MP(TFMP), CD142+) and (iii) phosphatidylserine(Annexin V+) was used. Plasma concentrations of thrombomodulin (TM), Tissue Factor (TF), Tissue factor pathway inhibitor (TFPI), Protein C (PC), Free Protein S (PS), Thrombin antithrombin (TAT) complexes, soluble fibrin monomer (sFM) was done assess the status of coagulation system. Spearman's rank correlation was done examine the role of cell-derived microparticles as critical effectors of thrombosis. Results: the study group comprised of 75% males of the age group (mean±SD27.3±4.32. Total Microparticles (Annexin V+) enumerated in plasma was 1125±355 (count/µl). 52.8% were TFMP [median (IQR)] [380.3(301.8-710.1) (count/µl)]. Highest number of MP originated from activated platelets [249.1(198.9-404.5) (count/µl)], followed by endothelial cells [140.9(124.9-286.0) (count/µl)]. A statistically significant and inverse correlation of EMP's with TAT complex was observed [12.7(6.8-20.1) ng/ml] (r = -0.46, p = 0.01), PS (93.4±20.6 %) (r = -0.52, p = 0.01) and TM (11.4±4.47 ng/ml) (r = -0.56, p = 0.008). Also, TFMP significantly correlated with TF [3.9(3.0-5.0)] (r = 0.46, p = 0.03) and PC (90.4±17.7) (r=-0.42, p=0.04). No correlation was observed between PMP numbers and coagulation pathway markers. Conclusion: Sub optimal degree of coagulation and natural anticoagulation pathway are occurring in healthy individuals. Microparticles moderately correlated with TF levels. Low EMP's levels correlated with the anticoagulation markers and thrombin generation, suggesting that EMPS may have a role in inhibition of thrombosis. The impact of endothelial vesiculation on basal coagulation should be studied further. Disclosures No relevant conflicts of interest to declare.

Abstract 350: Influence of HIV-1 Infection and Antiretroviral Therapy on the Coagulation System

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Kevin Fasing ◽  
Brian R Weil ◽  
Kyle J Diehl ◽  
Jared J Greiner ◽  
Brian L Stauffer ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Factor Viii ◽  
Tissue Factor ◽  
Plasma Concentrations ◽  
Tissue Type ◽  
Factor Vii ◽  
Coagulation System ◽  
Factor X ◽  
Thrombotic Risk ◽  
Hiv 1

HIV-1-infected individuals have a two- to four-fold greater incidence of cardiovascular disease and atherothrombotic events compared with the general population. The mechanisms responsible for this heightened cardiovascular risk are not fully understood. We have previously reported that the capacity of the endothelium to release tissue-type plasminogen activator (t-PA), the primary activator of fibrinolysis and a key endogenous defense mechanism against intravascular fibrin deposition and thrombosis, is impaired in HIV-1-seropositive adults. Whether diminished fibrinolytic activity is coupled with a hypercoagulative state in this population is unknown. Elevations in specific coagulation markers such as tissue factor and Factor VII are associated with increased thrombotic risk. The experimental aim of this study was to determine the influence of HIV-1 infection and antiretroviral therapy (ART) on markers of coagulation. To address this aim we studied 33 men: 16 HIV-1-seronegative (age: 41±3 yr); 7 HIV-1-seropositive treatment-naïve (34±2 yr); and 10 HIV-1-seropositive receiving ART (42±3 yr; efavirenz-based regimen). All subjects were non-obese, normotensive and free of overt cardiometabolic disease. Circulating concentrations of tissue factor, Factor VII, Factor VIII and Factor X were determined by immunoassay. There were no significant differences in plasma concentrations of tissue factor (32+3 vs 40+3 pg/mL), Factor VII (103+9 vs 100+5 %), Factor VIII (111+13 vs 117+8 %) and Factor X (89+5 vs 91+2 %) between HIV-1-seropositive treatment-naïve and healthy men. Moreover, there was no influence of ART on these circulating markers. Plasma tissue factor (41+5 pg/mL), Factor VII (107+6 %), Factor VIII (103+7 %) and Factor X (90+3%) were similar in the HIV-1-seropositive receiving ART compared with HIV-1-seropositive treatment-naïve and seronegative groups. These data suggest that neither HIV-1 infection per se nor ART are associated with unfavorable changes in specific coagulation markers. Thus, changes in the coagulation system that have been linked to increased thrombotic burden are not apparent in HIV-1-seropositive adults.

scholarly journals Expression of the JAK/STAT Signaling Pathway in Bullous Pemphigoid and Dermatitis Herpetiformis

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
K. Juczynska ◽  
A. Wozniacka ◽  
E. Waszczykowska ◽  
M. Danilewicz ◽  
M. Wagrowska-Danilewicz ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Bullous Pemphigoid ◽  
Target Genes ◽  
Dermatitis Herpetiformis ◽  
Skin Lesions ◽  
Control Group ◽  
Cytokine Network ◽  
Activation Of Transcription ◽  
Autoimmune Bullous Diseases ◽  
Stat Signaling

A family of eleven proteins comprises the Janus kinases (JAK) and signal transducers and activators of transcription (STAT) signaling pathway, which enables transduction of signal from cytokine receptor to the nucleus and activation of transcription of target genes. Irregular functioning of the cascade may contribute to pathogenesis of autoimmune diseases; however, there are no reports concerning autoimmune bullous diseases yet to be published. The aim of this study was to evaluate the expression of proteins constituting the JAK/STAT signaling pathway in skin lesions and perilesional area in dermatitis herpetiformis (DH) and bullous pemphigoid (BP), as well as in the control group. Skin biopsies were collected from 21 DH patients, from 20 BP patients, and from 10 healthy volunteers. The localization and expression of selected STAT and JAK proteins were examined by immunohistochemistry and immunoblotting. We found significantly higher expression of JAK/STAT proteins in skin lesions in patients with BP and DH, in comparison to perilesional skin and the control group, which may be related to proinflammatory cytokine network and induction of inflammatory infiltrate in tissues. Our findings suggest that differences in the JAK and STAT expression may be related to distinct cytokines activating them and mediating neutrophilic and/or eosinophilic infiltrate.

scholarly journals Factor IXa-factor VIIIa-cell surface complex does not contribute to the basal activation of the coagulation mechanism in vivo

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 2039-2047 ◽  
Author(s):  
KA Bauer ◽  
PM Mannucci ◽  
A Gringeri ◽  
F Tradati ◽  
S Barzegar ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Plasma Concentrations ◽  
Factor Ix ◽  
Factor Vii ◽  
Coagulation System ◽  
Activate Factor ◽  
Factor X ◽  
Factor Ixa ◽  
Tissue Factor Pathway ◽  
Activation Peptide

Abstract We have infused recombinant factor VIIa into patients with hereditary factor VII deficiency with marked reductions in plasma concentrations of factor IX activation peptide (FIXP), factor X activation peptide (FXP), and prothrombin activation fragment F1+2. These investigations show substantial elevations in these markers of coagulation activation and thereby demonstrate that the factor VII-tissue factor pathway is largely responsible for the activation of factor IX as well as factor X in the basal state (ie, the absence of thrombosis or provocative stimuli). We have administered a monoclonal antibody purified factor IX concentrate to individuals with hemophilia B. These studies show an increase in the plasma levels of FIXP that were initially greatly decreased, but no change in FXP or F1+2. We have also infused highly purified factor VIII concentrate into patients with hemophilia A. The data demonstrate no significant changes in the plasma concentrations of FXP and F1+2. The above observations indicate that factor IXa generated by the factor VII-tissue factor pathway is unable to activate factor X under basal conditions. Based upon the above findings, we outline a model of blood coagulation system function under basal conditions, and suggest a process by which the generation of factor Xa and thrombin might be accelerated during normal hemostasis and in the setting of thrombotic disorders.

scholarly journals The Expression of Selected Proapoptotic Molecules in Dermatitis Herpetiformis

2012 ◽  
Vol 2012 ◽  
pp. 1-6
Author(s):  
Zebrowska Agnieszka ◽  
Erkiert-Polguj Anna ◽  
Wagrowska-Danilewicz Malgorzata ◽  
Danilewicz Marian ◽  
Sysa-Jedrzejowska Anna ◽  
...  
Keyword(s):  
Fas Ligand ◽  
Dermatitis Herpetiformis ◽  
Single Cells ◽  
Skin Lesions ◽  
Control Group ◽  
Trail Expression ◽  
Skin Biopsies ◽  
And Control ◽  
Perilesional Skin

The role of the process of apoptosis is investigated in the pathogenesis of many autoimmune diseases; however at present, there is not much information about its role in dermatitis herpetiformis. Skin biopsies were taken from 18 DH patients and from 10 healthy subjects. The localization and expression of Bax, Fas, FasL, TRAIL, TRAIL-R in skin lesions, and perilesional skin were studied by immunohistochemistry. Expression of Bax, Fas, and Fas ligand was detected in the keratinocytes in skin biopsies from DH patients. Expression of TRAIL and TRAIL receptor was confirmed in epidermis, infiltration cells, and some fibroblasts. The expression of examined molecules in biopsies from healthy people was observed only in single cells. There were statistically significant differences between lesional, perilesional, and healthy skin of control group in Bax expression analysis and between lesional skin and control group in Fas, FasL, and TRAIL expression. There were statistically significant differences between control group and perilesional skin in Bax and FasL expression. Our results show that selected proapoptotic molecules may take part in pathogenesis of dermatitis herpetiformis, but the role of apoptosis in this process is not clear.

scholarly journals Factor IXa-factor VIIIa-cell surface complex does not contribute to the basal activation of the coagulation mechanism in vivo

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 2039-2047
Author(s):  
KA Bauer ◽  
PM Mannucci ◽  
A Gringeri ◽  
F Tradati ◽  
S Barzegar ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Plasma Concentrations ◽  
Factor Ix ◽  
Factor Vii ◽  
Coagulation System ◽  
Activate Factor ◽  
Factor X ◽  
Factor Ixa ◽  
Tissue Factor Pathway ◽  
Activation Peptide

We have infused recombinant factor VIIa into patients with hereditary factor VII deficiency with marked reductions in plasma concentrations of factor IX activation peptide (FIXP), factor X activation peptide (FXP), and prothrombin activation fragment F1+2. These investigations show substantial elevations in these markers of coagulation activation and thereby demonstrate that the factor VII-tissue factor pathway is largely responsible for the activation of factor IX as well as factor X in the basal state (ie, the absence of thrombosis or provocative stimuli). We have administered a monoclonal antibody purified factor IX concentrate to individuals with hemophilia B. These studies show an increase in the plasma levels of FIXP that were initially greatly decreased, but no change in FXP or F1+2. We have also infused highly purified factor VIII concentrate into patients with hemophilia A. The data demonstrate no significant changes in the plasma concentrations of FXP and F1+2. The above observations indicate that factor IXa generated by the factor VII-tissue factor pathway is unable to activate factor X under basal conditions. Based upon the above findings, we outline a model of blood coagulation system function under basal conditions, and suggest a process by which the generation of factor Xa and thrombin might be accelerated during normal hemostasis and in the setting of thrombotic disorders.

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