fibrin and Behcet-Syndrome

The fibrinolytic system comprises a proenzyme, plasminogen, which can be activated to the active enzyme plasmin, that will degrade fibrin by different types of plasminogen activators. Inhibition of fibrinolysis may occur at the level of plasmin or at the level of the activators. Fibrinolysis in human blood seems to be regulated by specific molecular interactions between these components. In plasma, normally no systemic plasminogen activation occurs. When fibrin is formed, small amounts of plasminogen activator and plasminogen adsorb to the fibrin, and plasmin is generated in situ. The formed plasmin, which remains transiently complexed to fibrin, is only slowly inactivated by alpha 2-antiplasmin, while plasmin, which is released from digested fibrin, is rapidly and irreversibly neutralized. The fibrinolytic process, thus, seems to be triggered by and confined to fibrin. Thrombus formation may occur as the result of insufficient activation of the fibrinolytic system and (or) the presence of excess inhibitors, while excessive activation and/or deficiency of inhibitors might cause excessive plasmin formation and a bleeding tendency. Evidence obtained in animal models suggests that tissue-type plasminogen activator, obtained by recombinant DNA technology, may constitute a specific clot-selective thrombolytic agent with higher specific activity and fewer side effects than those currently in use.

Topics: alpha-2-Antiplasmin; alpha-Macroglobulins; Animals; Behcet Syndrome; Binding Sites; Disseminated Intravascular Coagulation; Embolism; Female; Fibrin; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Humans; In Vitro Techniques; Kidney Diseases; Kinetics; Liver Diseases; Lysine; Plasminogen; Plasminogen Activators; Plasminogen Inactivators; Pregnancy; Streptokinase; Thrombosis; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

Topics: Adult; Bacteria; Behcet Syndrome; Butyrates; Diet, Vegetarian; Female; Fermentation; Fibrin; Fibrinolysis; Gastrointestinal Microbiome; Humans; Lipid Peroxidation; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Proof of Concept Study; Reactive Oxygen Species; Time Factors; Treatment Outcome

Plasminogen serves as the precursor to plasmin, an essential element in the fibrinolytic process, and is synthesized primarily in the liver. Plasminogen activation occurs through the action of plasminogen activator, converting it into plasmin. This conversion greatly enhances the fibrinolytic system within tissues and blood vessels, facilitating the dissolution of fibrin clots. Consequently, congenital deficiency of plasminogen results in impaired fibrin degradation. Patients with plasminogen deficiency typically exhibit fibrin deposits in various mucosal sites throughout the body, including the oral cavity, eyes, vagina, and digestive organs. Behcet's disease is a chronic recurrent systemic inflammatory disease with four main symptoms: aphthous ulcers of the oral mucosa, vulvar ulcers, skin symptoms, and eye symptoms, and has been reported worldwide. This disease is highly prevalent around the Silk Road from the Mediterranean to East Asia. We report a case of periodontitis in a patient with these two rare diseases that worsened quickly, leading to alveolar bone destruction. Genetic testing revealed a novel variant characterized by a stop-gain mutation, which may be a previously unidentified etiologic gene associated with decreased plasminogen activity.. This case report depicts a patient diagnosed with ligneous gingivitis during childhood, originating from plasminogen deficiency and progressing to periodontitis. Genetic testing revealed a suspected association with the PLG c.1468C > T (p.Arg490*) stop-gain mutation. The patient's periodontal condition remained stable with brief intervals of supportive periodontal therapy. However, the emergence of Behçet's disease induced acute systemic inflammation, necessitating hospitalization and treatment with steroids. During hospitalization, the dental approach focused on maintaining oral hygiene and alleviating contact-related pain. The patient's overall health improved with inpatient care and the periodontal tissues deteriorated.. Collaborative efforts between medical and dental professionals are paramount in comprehensively evaluating and treating patients with intricate complications from rare diseases. Furthermore, the PLG c.1468C > T (p.Arg490*) stop-gain mutation could contribute to the association between plasminogen deficiency and related conditions.

Topics: Behcet Syndrome; Female; Fibrin; Fibrinolysin; Humans; Periodontitis; Plasminogen; Rare Diseases

Topics: Apoptosis; Behcet Syndrome; Extracellular Traps; Fibrin; Humans; Necrosis; Neutrophils; Protein-Arginine Deiminase Type 4; Reactive Oxygen Species; Thrombin; Thrombosis

Data regarding biomarkers to understand disease pathogenesis and to assess disease activity of intestinal Behçet's disease (BD) are limited. Therefore, we aimed to investigate the differentially expressed proteins in sera from patients with intestinal BD and to search for biomarkers using mass spectrometry-based proteomic analysis.. Serum samples were pooled for the screening study, and two-dimensional electrophoresis (2-DE) was performed to characterize the proteins present in intestinal BD patients. Candidate protein spots were identified using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF MS) and bioinformatic analysis. To validate the proteomic results, serum samples from an independent cohort were assessed by enzyme-linked immunosorbent assay.. Pooled serum samples were used for 2-DE, and approximately 400 protein spots were detected in the sera of intestinal BD patients. Of the 22 differentially expressed proteins, 3 were successfully identified using MALDI-TOF/TOF MS. The three up-regulated proteins identified in the intestinal BD group included fibrin, apolipoprotein A-IV, and serum amyloid A (SAA). Serum SAA in intestinal BD patients (2.76 ± 2.50 ng/ml) was significantly higher than that in controls (1.68 ± 0.90 ng/ml, p = 0.007), which is consistent with the proteomic results. In addition, the level of IL-1β in patients with intestinal BD (8.96 ± 1.23 pg/ml) was higher than that in controls (5.40 ± 0.15 pg/ml, p = 0.009). SAA released by HT-29 cells was markedly increased by tumor necrosis factor-α (TNF-α) and lipopolysaccharides stimulation.. Our proteomic analysis revealed that SAA was up-regulated in intestinal BD patients.

Topics: Adult; Apolipoproteins A; Behcet Syndrome; Biomarkers; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Fibrin; HT29 Cells; Humans; Interleukin-1beta; Intestinal Diseases; Male; Mass Spectrometry; Middle Aged; Proteomics; Serum Amyloid A Protein

A 33-year-old male with definite Behçet's disease had rheumatoid-like nodules at his elbows. This finding, we believe, represents another manifestation of vasculitis in Behçet's disease.

Topics: Adult; Behcet Syndrome; Fibrin; Humans; Male; Neutrophils; Rheumatoid Nodule; Ulna

A kidney and lung biopsy were performed on a patient with active Behçet's disease with renal and pulmonary involvement. Histologic, immunohistochemical and electron microscopic studies of the kidney biopsy specimen revealed a focal segmental necrotizing glomerulonephritis characterized by the presence of numerous subendothelial and occasional intramembranous deposits containing immunoglobulin G (IgG), the third component of complement (C3), the fourth component of complement (C4) and fibrin(ogen). Histologic and immunohistochemical studies of the lung biopsy specimen showed an acute venulitis and septal capillaritis associated with the presence of identical deposits within the walls of affected vessels. Circulating immune complexes were detected in the patient's serum by Raji cell assay. The findings indicate that the glomerulonephritis and pulmonary vasculitis occasionally occurring in Behçet's disease are due to the deposition of circulating antigen-antibody complexes. In addition, they strongly suggest that the majority of the major and minor manifestations of the disease, such as uveitis, cutaneous vasculitis, synovitis and meningoencephalitis, are a result of vascular immune complex deposition.

Topics: Behcet Syndrome; Capillaries; Complement C3; Complement C4; Female; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Immune Complex Diseases; Immunoglobulin G; Kidney Glomerulus; Lung; Middle Aged; Pulmonary Alveoli; Pulmonary Circulation; Vasculitis

Suppression of the fibrinolytic system is a well-known phenomenon in patients with Behçet's disease. It is generally explained by an increase in the inhibitory potential. In order to prove this theory, the fibrinolytic system was investigated in 5 male patients with severe chronic Behçet's disease. By the venous occlusion test, a marked suppression of the activatability of the system could be demonstrated (euglobulin lysis time, various fibrin plate assays). Results of analysis of the known inhibitors could not explain the phenomenon: antithrombin III, alpha2-macroglobulin, fast-reacting alpha2-antiplasmin, C1 inactivator, and the plasmin-antiplasmin complex were normal. The only change was an elevation of alpha1-antitrypsin and fibrinogen in 4 patients possibly due to an acute phase reaction. In addition to the possibility of a hitherto unidentified inhibitor, therefore, a decrease in production or in release of vessel wall activators must also be considered in the pathogenesis of this disorder.

Topics: Adult; Antifibrinolytic Agents; Behcet Syndrome; Fibrin; Fibrinogen; Humans; Male; Plasminogen; Serum Globulins

Topics: Adolescent; Adult; Behcet Syndrome; Female; Fibrin; Fibrinogen; Humans; Male; Middle Aged; Thrombophlebitis

Topics: Behcet Syndrome; Fibrin; Fibrinolysis; Hemagglutination Inhibition Tests; Humans

Topics: Animals; Behcet Syndrome; Collagen; Collagen Diseases; Cornea; Eye; Eye Diseases; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Glaucoma; Humans; Rabbits; Uveitis