fibrin and Rheumatic-Diseases

Activation of the immune system has been increasingly recognised to be associated with procoagulatory status in patients with inflammatory rheumatic disease. Changes in endothelial cell and platelet activation, blood flow, expression and activity of different coagulation factors, and impaired fibrinolysis serve as pathophysiological basis for enhanced risk of venous thromboembolism in inflammatory rheumatic diseases, such as rheumatoid arthritis (RA), connective tissue diseases and vasculitides. Recent studies identifying mechanisms for a functional role of coagulation factors beyond haemostasis have provided examples of interesting links between the coagulation system and innate immune activation. Furthermore, citrullinated fibrinogen is an important and early autoantigen in patients with RA carrying the HLA-DRβ1 shared epitope allele, which demonstrates an adaptive immune response to a coagulation factor in an inflammatory rheumatic disease. Additional studies have provided strong evidence that a multitude of different components of the haemostatic system (such as thrombin, fibrinogen, coagulation factor XIII and factors of the fibrinolytic system) are relevant mediators of inflammatory processes as well as of inflammatory control. Understanding the interactions between coagulation and the immune system in inflammatory rheumatic diseases will not only improve our knowledge of disease mechanisms, but could also permit the development of innovative therapeutic interventions.

Topics: Blood Coagulation; Endothelium, Vascular; Female; Fibrin; Hemostasis; Humans; Immunity, Innate; Male; Platelet Activation; Rheumatic Diseases; Venous Thromboembolism

Topics: Enzymes; Fatty Acids, Nonesterified; Fibrin; Fibrinogen; Glycosaminoglycans; Histocytochemistry; Humans; Hyaluronic Acid; Immunoglobulins; Prostaglandins E; Proteins; Rheumatic Diseases; Rheumatoid Factor; Synovial Fluid

Topics: Animals; Antigens; Arthritis, Rheumatoid; Autoimmune Diseases; Cartilage; Cattle; Cell Membrane Permeability; Densitometry; Esterases; Fibrin; Fibrinolysis; Histocytochemistry; Humans; Hyaluronoglucosaminidase; Hydrocortisone; Inflammation; Kinins; Leukocytes; Lysosomes; Mice; Microscopy, Electron; Neuraminidase; Oxidation-Reduction; Peptide Hydrolases; Phagocytosis; Phosphoric Monoester Hydrolases; Pinocytosis; Proteins; Rabbits; Rats; Rheumatic Diseases; Synovial Membrane; Synovitis

To evaluate the proportions of rheumatoid arthritis (RA) sera containing anticitrullinated proteins autoantibodies (ACPA) reactive to α36-50Cit₃₈,₄₂ and/or β60-74Cit₆₀,₇₂,₇₄, two peptides identified as bearing the immunodominant epitopes of their major target, citrullinated fibrin. To analyse the relationships of anti-α36-50Cit₃₈,₄₂ and anti-β60-74Cit₆₀,₇₂,₇₄ autoantibodies with autoantibodies reactive to the complete citrullinated human fibrinogen molecule (AhFibA) and with anti-CCP2 antibodies.. 617 sera from 181 patients with established RA and 436 with non-RA rheumatic diseases were tested by ELISA for AhFibA, anti-CCP2, anti-α36-50Cit₃₈,₄₂, anti-β60-74Cit₆₀,₇₂,₇₄ autoantibodies, and by nephelometry for rheumatoid factor (RF). Diagnostic indexes, correlations and concordances between tests were analysed. Crossreactivity of anti-α36-50Cit₃₈,₄₂ and anti-β60-74Cit₆₀,₇₂,₇₄ autoantibodies was assessed in competition experiments.. At a diagnostic specificity of 95%, the diagnostic sensitivity of AhFibA (83%) was significantly higher than that of all other tests. The diagnostic sensitivity of anti-β60-74Cit₆₀,₇₂,₇₄ (71%) was significantly higher than that of anti-α36-50Cit₃₈,₄₂ autoantibodies (51%) but similar to that of anti-CCP2 (74%). Titres of RF, anti-α36-50Cit₃₈,₄₂ and anti-β60-74Cit₆₀,₇₂,₇₄ autoantibodies were weakly correlated with each other, whereas titres of anti-β60-74Cit₆₀,₇₂,₇₄ were strongly correlated with those of AhFibA (r=0.633) and anti-CCP2 (r=0.634). Anti-α36-50Cit₃₈,₄₂ and anti-β60-74Cit₆₀,₇₂,₇₄ mainly corresponded to two non-crossreactive subfamilies of ACPA. More than 90% of AhFibA-positive or anti-CCP2-positive sera recognised the α36-50Cit₃₈,₄₂ and/or the β60-74Cit₆₀,₇₂,₇₄ peptide.. Autoantibodies reactive to α36-50Cit₃₈,₄₂ and β60-74Cit₆₀,₇₂,₇₄ form two distinct, non-overlapping subfamilies of ACPA that, together, cover practically all the ACPA reactivity to citrullinated fibrinogen and to CCP2 antigens. In established RA, anti-β60-74Cit₆₀,₇₂,₇₄ autoantibodies show diagnostic indexes similar to those of anti-CCP2.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Autoantibodies; Case-Control Studies; Citrulline; Epitopes; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Male; Middle Aged; Peptide Fragments; Peptides, Cyclic; Rheumatic Diseases; Rheumatoid Factor; Young Adult

Abnormal plasminogen activation has been implicated in vascular and rheumatic diseases. The development of an autoimmune response to neoepitopes of plasminogen and its activator (tissue-type plasminogen activator, t-PA) was explored in sera from patients with rheumatoid arthritis (RA, n = 30), Behcet's disease (n = 20), primary antiphospholipid syndrome (APS, n = 23), and idiopathic arterial (n = 33) or venous thrombosis (n = 16).. Sera diluted 1/50 were incubated with either plasminogen or t-PA bound to their natural receptors (immobilized fibrin or monocytic cells), and bound immunoglobulins were detected using a sheep peroxidase labeled anti-human Fab IgG. Controls included plates coated with fibrin or cells alone or plasminogen passively adsorbed to the plastic. Sera were considered positive when the absorbance at 405/490 nm was above the mean + 2 SD of normal sera.. Reactivity of sera against plasminogen bound to cells (28%) or to fibrin (22%) was a predominant feature in patients with RA compared with other patient groups and controls. However, some patients with primary APS had reactivity against cell and fibrin bound plasminogen (9 and 13%, respectively). Autoantibodies against fibrin bound t-PA were detected in only 8% of patients with arterial or venous thrombosis.. Conformational changes induced by molecular assembly of plasminogen on cell or fibrin surfaces result in the expression of neoepitopes recognized by autoantibodies. These autoantibodies could be markers of the proteolytic events associated with plasminogen activation in autoimmune diseases.

Topics: Adult; Antigen-Antibody Complex; Antigens; Autoantibodies; Binding Sites, Antibody; Cell Line; Epitopes; Fibrin; Humans; Middle Aged; Plasminogen; Receptors, Cell Surface; Rheumatic Diseases; Tissue Plasminogen Activator; Vascular Diseases

Topics: Diagnosis, Differential; Female; Fibrin; Humans; Magnetic Resonance Imaging; Middle Aged; Rheumatic Diseases; Shoulder

Topics: Animals; Endocarditis; Fibrin; Haplorhini; Humans; Male; Myocarditis; Rheumatic Diseases; Rheumatic Heart Disease; Streptococcus; Toxins, Biological

Topics: Adolescent; Adult; Aspartate Aminotransferases; Child; Child, Preschool; DNA; Female; Fibrin; Humans; Male; Middle Aged; Plasma; Rheumatic Diseases; Tonsillitis

Topics: Allergy and Immunology; Animals; Antigen-Antibody Reactions; Arthritis; Arthritis, Rheumatoid; Fibrin; Haplorhini; Humans; Pathology; Rheumatic Diseases; Rheumatoid Factor; Rheumatoid Nodule

Topics: Chromatography; Fibrin; gamma-Globulins; Gelatin; Peptides; Proteins; Rats; Research; Rheumatic Diseases; Rheumatoid Nodule; Serum Albumin; Trypsin

Topics: Fibrin; Humans; Inflammation; Rheumatic Diseases

Topics: Aniline Compounds; Arthritis; Arthritis, Rheumatoid; Blood Sedimentation; Diagnosis; Diphenylamine; Fibrin; Leukocytosis; Leukopenia; Rheumatic Diseases; Tonsillitis

Topics: Coagulants; Fibrin; Fibrinogen; Hemostatics; Polysaccharides; Rheumatic Diseases

Topics: Fibrin; Rheumatic Diseases

Topics: Arteriosclerosis; Coagulants; Fibrin; Fibrinogen; Hemostatics; Humans; Rheumatic Diseases; Thrombosis

Topics: Arthritis; Arthritis, Rheumatoid; Fibrin; Humans; Rheumatic Diseases

Topics: Fibrin; Rheumatic Diseases; Solubility; Thrombosis