elastin and Giant-Cell-Arteritis

Studies of autoimmune diseases have not yet elucidated why certain organs or vessels become the objects of injury while others are spared. This paper explores the hypothesis that important differences exist in regions of the aorta; these regional variations determine vulnerability to such diseases as atherosclerosis, aortitis, giant-cell arteritis, and Takayasu's disease. The reader is invited to reassess two issues: (1) whether the aorta is indeed a single homogeneous structure; and (2) whether the initial stage of aortitis (and indeed other diseases considered "autoimmune") may primarily be the result of acquired alterations of substrate that influence unique immune profiles, but that by themselves may not be pathogenic. Disease susceptibility and patterns are influenced by many factors that are either inborn or acquired. Examples include genetic background, gender, ethnicity, aging, prior and concomitant illnesses, habits, diet, and exposure to toxins and other environmental hazards. Studies of vascular diseases must assess how such variables affect regional anatomic differences in endothelial cells, subendothelial matrix, and vascular smooth muscle, as well as the response of each to a variety of stimuli.

Topics: Aging; Animals; Aortitis; Atherosclerosis; Collagen; Disease Models, Animal; Elastin; Giant Cell Arteritis; Humans; Immune System; Takayasu Arteritis; Vasculitis

Histological analysis of giant cell arteritis (GCA) reveals a granulomatous reaction around the internal elastic lamina. Elastolysis by multinucleated giant cells has also been reported. We investigated elastin derived peptides as putative recall antigens for peripheral blood mononuclear cells (PBMC) from patients with GCA.. PBMC were collected from 17 patients with GCA (Group 1), 17 patients with vascular diseases, connective tissue diseases, or polymyalgia rheumatica without GCA (Group 2), and 17 healthy controls (Group 3). Cultures of PBMC with different elastin derived peptides or elastase were analyzed.. A proliferative response was obtained only with elastate derived elastin peptides in 12/13 untreated patients with GCA. Steroid treatment was believed to abolish this proliferative response in 4 patients with GCA. PBMC from only 3/34 non-GCA subjects responded to these antigens. No proliferative response was obtained for other elastin derived peptides or elastase in any subject.. Degradation of native elastin by leukocyte elastase can provide elastin derived peptides that act as autoimmune targets for T cells in GCA.

Topics: Adrenal Cortex Hormones; Aged; Aged, 80 and over; Autoimmunity; Elastin; Female; Giant Cell Arteritis; Humans; Leukocyte Elastase; Lymphocyte Activation; Male; Middle Aged; Peptides; T-Lymphocytes

The elastin peptide level (EP) and elastase-type activity (EA) were investigated in 89 patients with different types of systemic vasculitis (polyarteritis nodosa-14, non-specific aortoarteritis-33, temporal arteritis-23 and thromboangiitis obliterans-18) and compared to the controls: 31 patients with leg atherosclerosis and 12 aged subjects with no evident vascular pathology. EP and EA levels in patients with thromboangiitis obliterans were significantly lower as compared to leg atherosclerosis and the aged control group (p < 0.02 for EA, p < 0.05 for EP). The increase of EP predominated in giant-cell arteritis as compared to the other vasculitic groups (18/56 vs. 5/32, p < 0.05); EA in these patients was the lowest. The activation of elastin degradation after corticosteroid treatment was demonstrated by an increase of EP in temporal arteritis (p < 0.05) and of EA in thromboangiitis obliterans (p < 0.03). We suggest that the determination of the above parameters of elastin degradation may be helpful in the search for differences in mechanisms of vascular damage between atherosclerosis and inflammatory vascular diseases.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aortitis; Arteriosclerosis; Elastin; Female; Giant Cell Arteritis; Humans; Male; Middle Aged; Pancreatic Elastase; Peptides; Polyarteritis Nodosa; Reference Values; Thromboangiitis Obliterans

Topics: Adult; Aged; Autoantibodies; Carotid Artery Diseases; Cerebral Infarction; Cerebrovascular Disorders; Complement System Proteins; Elastin; Giant Cell Arteritis; Humans; Immune Complex Diseases; Immunoglobulins; Male; Middle Aged; Temporal Arteries

There is much evidence to suggest that temporal arteritis and rhizomelic polymyalgia are both immunological diseases. The classic results of experimental pathology are discussed, together with the relations between rhizomelic polymyalgia and both virus hepatitis B and the HLA system. From the clinical standpoint, it is now agreed that differences in individual response may lead to either a synovial or an arteritic response in both forms. Their association in what Hamrin has called "polymyalgia arteritica" is also common.

Topics: Antigen-Antibody Complex; Antigens, Viral; Elastin; Giant Cell Arteritis; Hepatitis B; Hepatitis B virus; HLA Antigens; Humans; Hypersensitivity, Delayed; Polymyalgia Rheumatica

This study of cutaneous elastic tissue and serum fluorescence supports the hypothesis that widespread destruction and resorption of elastic tissue (elastolysis) occurs in the temporal arteritis/polymyalgia rheumatica syndrome. A systemic elastolysis of this nature may be provoked by actinic (radiant) damage to the "exposed" elastic tissues in the skin and superficial arteries, the archetype of such injury being seen in temporal arteritis. Scattered giant cells are the usual agents of elastolysis but tuberculoid ("sarcoid") infiltrates often take over in the later stages. In acute polymyalgia, the phenomenon probably becomes diffuse and humoral. Elastolysis may be a direct pathogenetic link between polymyalgia and other vascular diseases such as idiopathic aneurysm and atherosclerosis.

Topics: Blood Protein Electrophoresis; Elastic Tissue; Elastin; Female; Fluorescence; Giant Cell Arteritis; Haptoglobins; Humans; Male; Polymyalgia Rheumatica; Skin; Ultraviolet Rays

Actinic damage (actinic elastosis) affecting the internal elastic lamina appears to be the prime cause of 'age change' and arteritis of the temporal artery. Resorption and removal of altered elastin (elastolysis) is an integral part of the pathology of actinic damage. Actinic irradiation is probably responsible for the destruction and disappearance of a vast number of arterioles in elastotic skin. The intimate connection between temporal arteritis and polymyalgia rheumatica prompts the belief that the vascular and other internal malign components of the temporal arteritis/polymyalgia rheumatica syndrome might likewise be due, albeit indirectly, to the same actinic cause. Actinic elastotic damage at the body surface could have this effect by provoking a state of systemic elastolysis. Although ultraviolet (uv) light is often regarded as the sole cause of actinic elastosis, penetrating infrared (heat) irradiation may deserve a large or even a dominant share of the blame.

Topics: Adult; Aged; Arterioles; Elastic Tissue; Elastin; Female; Giant Cell Arteritis; Humans; Male; Middle Aged; Polymyalgia Rheumatica; Skin; Sunlight; Temporal Arteries

Topics: Antigen-Antibody Complex; Elastin; Female; Giant Cell Arteritis; Humans; Immunoglobulins; Male; Microscopy, Electron; Temporal Arteries

Topics: Arteritis; Cell Migration Inhibition; Collagen Diseases; Elastin; Giant Cell Arteritis; Humans; Immunity, Cellular; Leukocytes; Polyarteritis Nodosa; Scleroderma, Systemic; Takayasu Arteritis; Vascular Diseases

Topics: Aged; Animals; Antibodies, Antinuclear; Antigen-Antibody Complex; Biopsy; Cell Nucleus; Cytoplasm; Elastic Tissue; Elastin; Female; Fluorescent Antibody Technique; Giant Cell Arteritis; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Male; Microscopy; Middle Aged; Rabbits; Temporal Arteries; Vascular Diseases