fibrin and Giant-Cell-Arteritis

Cranial and extra-cranial vascular events are among the major determinants of morbidity and mortality in Giant Cell Arteritis (GCA). Vascular events seem mostly of inflammatory nature, although the precise pathogenetic mechanisms are still unclear. We investigated the role of oxidation-induced structural and functional fibrinogen modifications in GCA. The effects of the anti-IL6R tocilizumab in counteracting these mechanisms were also assessed.. A cross-sectional study was conducted on 65 GCA patients and 65 matched controls. Leucocyte reactive oxygen species (ROS) production, redox state, and fibrinogen structural and functional features were compared between patients and controls. In 19 patients receiving tocilizumab, pre vs post treatment variations were assessed.. GCA patients displayed enhanced blood lymphocyte, monocyte and neutrophil ROS production compared to controls, with an increased plasma lipid peroxidation and a reduced total antioxidant capacity. This oxidative impairment resulted in a sustained fibrinogen oxidation (i.e. dityrosine content 320 (204-410) vs 136 (120-176) Relative Fluorescence Units (RFU), p < 0.0001), with marked alterations in fibrinogen secondary and tertiary structure [intrinsic fluorescence: 134 (101-227) vs 400 (366-433) RFU, p < 0.001]. Structural alterations paralleled a remarkable fibrinogen functional impairment, with a reduced ability to polymerize into fibrin and a lower fibrin susceptibility to plasmin-induced lysis. In patients receiving tocilizumab, a significant improvement in redox status was observed, accompanied by a significant improvement in fibrinogen structural and functional features (p < 0.001).. An impaired redox status accounts for structural and functional fibrinogen modifications in GCA, suggesting a potential role of tocilizumab for cardiovascular prevention in GCA.

Topics: Cross-Sectional Studies; Fibrin; Fibrinogen; Giant Cell Arteritis; Hemostatics; Humans; Interleukin-6; Reactive Oxygen Species

Hepatic fibrin-ring granulomas were found in a 70-year-old man with prolonged fever and inflammatory syndrome. Diagnosis of giant cell arteritis was confirmed by temporal artery biopsy. Other diseases usually associated with fibrin-ring granulomas in liver, such as Q fever, cytomegalovirus hepatitis, infectious mononucleosis, Hodgkin's disease, non-Hodgkin's lymphoma, allopurinol treatment, and visceral leishmaniasis, were ruled out. This report suggests that giant cell arteritis should be considered as an additional cause of hepatic fibrin-ring granulomas.

Topics: Aged; Fibrin; Giant Cell Arteritis; Granuloma; Humans; Liver; Liver Diseases; Male

Temporal arteritis is a systmic disease with a predilecation for the cranio-temporal vascular area. Histologically it is a panarteritis. Diagnosis is based on the presence of lymphocytes, histiocytes and foci of epitheloid cells in the media of the temporal artery. The presence of giant cells is, however not obligatory. The present study emphasizes the value of biopsy of the temporal artery in diagnosing this disease. It, furthermore, also points out the 10-percent possibility of false negative biopsy results based on patchy vascular lesions. Tenderness to touch of the temporal artery, characteristic of temporal arteriitis, can be explained by perineural inflammatory infiltration of nerves in the adventitia of this artery. Examination under the electron microscope reveals almost complete destruction of the smooth muscles of the media by epitheloid cell granulomas. Massive neogenesis of collagen ensues. Furthermore, numerous myofibroblasts, macrophages and histiocytes are observed. Several macrophages close to each other create the impression of giant cells in the light microscope. The electron microscope image allows for clear differentiation between temporal arteritis on one hand and of arteriosclerosis on the other. Using the immunoperoxidase method in temporal arteritis, immune globulines are found intracellularly in plasma cells. Extracellularly, however, neither immune golbulins nor complement deposits are found in the vascular wall. Thus, the assumption that temporal arteritis represents a immune complex disorder cannot be maintained. The most frequent ophthalmologic complication in temporal arteritis is ischemic optic neuropathy. Histologic examination of a bulbus presenting anterior ischemic optic neuropathy in a case of temporal arteritis revealed predominantly lymphocytic infiltrations of the short and long ciliary arteries. No inflammatory infiltration was found in the central retinal artery. The development of anterior ischemic optic neuropathy can be explained by impaired perfusion or by occlusion of the short posterior ciliary arteries. In 60% of patients suffering from temporal arteritis, we found anticollagen antibodies in the serum. Collagenization of the vascular wall as observed in our electron-microscopic examinations must, therefore, be considered the paradoxical consequence of an immune reaction caused by collagen auto-antibodies. Collagen auto-antibodies play a decisive role in the maintenance and chronicity of the inflammatory proc

Topics: Aged; Complement Activating Enzymes; Complement C1q; Complement C3; Female; Fibrin; Giant Cell Arteritis; Humans; Immunoenzyme Techniques; Immunoglobulin G; Male; Microscopy, Electron; Middle Aged; Temporal Arteries

The cause of cranial arteritis is unknown, but the demonstration of immunoglobulin and complement in temporal artery biopsies by immunofluorescence suggest that it may be a disease of disordered immunity. Because of the inevitable problems of histologic interpretation associated with the fluorescent technique, 15 temporal artery biopsies from patients with active arteritis were examined by an immunoperoxidase method. Varying amounts of IgA, IgG, and IgM were identified in plasma cells and macrophages. Extracellular IgG was identified in 1 case, but there was no staining for complement. These findings provide no support for the concept of cranial arteritis as a form of immune complex vasculitis.

Topics: Aged; Animals; Female; Fibrin; Giant Cell Arteritis; Humans; Immune Sera; Immunoglobulin G; Immunoglobulin M; Macrophages; Male; Middle Aged; Rabbits

Topics: Adrenal Cortex Hormones; Arthritis, Rheumatoid; Cartilage; Collagen Diseases; Connective Tissue; Dermatomyositis; Fibrin; Giant Cell Arteritis; Humans; Lupus Erythematosus, Systemic; Rheumatic Fever; Scleroderma, Systemic