Decreased fibrinolytic potential and morphological changes of fibrin structure in dermatitis herpetiformis

• Published in: Journal of dermatological science Vol. 84; no. 1; pp. 17 - 23
• Main Authors: Görög, Anna, Németh, Krisztián, Szabó, László, Mayer, Balázs, Silló, Pálma, Kolev, Krasimir, Kárpáti, Sarolta
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2016
• Subjects: Adult; Aged; Blood Coagulation; Case-Control Studies; Cryoglobulinemia - blood; Dapsone; Dapsone - therapeutic use; Dermatitis herpetiformis; Dermatitis Herpetiformis - blood; Dermatitis Herpetiformis - drug therapy; Dermatology; Enzyme-Linked Immunosorbent Assay; Female; Fibrin; Fibrin - chemistry; Fibrinogen - chemistry; Fibrinolysis; Fluorescent Antibody Technique, Direct; Humans; Kinetics; Male; Microscopy, Electron, Scanning; Middle Aged; Nephelometry and Turbidimetry; Skin - metabolism; Transglutaminase 3; Young Adult; AB; TG3; DH; GFD; tPA; Dapsone; Transglutaminase 3; Dermatitis herpetiformis; Fibrinolysis; Fibrin; TG; EMA; SEM; Ig; ELISA; antibody/antibodies; endomysial antibodies; gluten-free diet; immunoglobulin; tissue plasminogen activator; epidermal transglutaminase; Scanning Electron Microscopy; enzyme-linked immunosorbent assay; transglutaminase TG2 tissue transglutaminase; dermatitis herpetiformis
• ISSN: 0923-1811; 1873-569X; 1873-569X
• DOI: 10.1016/j.jdermsci.2016.07.005

•A kinetic turbidity assay indicated delayed lysis in plasma clots from DH patients.•The modified turbidity of DH plasma clots suggested an altered fibrin structure.•Scanning electron microscopy confirmed structural changes of fibrin network in DH.•Dapsone had a favourable effect to fibrinolysis and fibrin structure.•Data indicate new factors in DH skin symptom development and dapsone effectivity. Recently, high prevalence of cryofibrinogenaemia has been observed in plasma of untreated dermatitis herpetiformis (DH) patients, and the pathological IgA and TG3 deposits in the papillary dermis were found to co-localize with fibrin and fibrinogen. To study the fibrinolytic potential in plasma of untreated, dapsone and or/gluten-free diet treated DH patients as well as the in vitro effect of dapsone on the fibrinolytic profile. Plasma samples of 23 DH patients, 19 healthy subjects and 5 pemphigus vulgaris patients were investigated by a turbidimetric-clot lysis assay. Out of them 5 DH plasma samples representing different fibrinolytic parameters, and 3 healthy controls were selected for parallel fibrin clot preparation. The clot fibrin structure was examined by scanning electron microscopy (SEM), and the diameters of 900 fibrin fibres were determined in each clot. A significantly prolonged clot lysis time was detected in untreated DH patients. The turbidity values of DH plasma clots indicated an altered fibrin structure that was also confirmed by SEM: significantly thicker fibrin fibers were observed in untreated, TG3 antibody positive DH patients compared to healthy controls, whereas the fiber diameters of dapsone-treated patients were similar or thinner than the control values. In line with the structural changes of fibrin, the fibrinolytic profile of 5 DH patients under dapsone treatment approached the control values. This study revealed that the fibrinolytic potential was impaired in the plasma of untreated DH patients, whereas dapsone corrected the fibrinolytic defect. These data suggest a pathogenic role for plasma-derived factors in the development of skin symptoms and add a new aspect to the long-known beneficial, symptomatic effect of dapsone in active DH.