elastin and Autoimmune-Diseases

Elastic fibres are an important component of connective tissue. They are composed of two elements: protein-elastin and microfibrils. Tissue rich in elastin include: aorta and major vessels, lungs, ligaments, tendons and skin. Elastases are a group of enzymes, which are able to degrade elastin. They are liberated from different cells including granulocytes, monocytes, lymphocytes, skin fibroblasts, cancer cells and others. The product of elastin degradation is known as elastin-derived peptides (EDP) and is a marker of elastolysis. Elastin-derived peptides are thought to act on elastin-laminin receptor (ELR), which is located on membrane of fibroblasts, granulocytes, lymphocytes, monocytes and' cancer cells. An increased elastin turnover can occur in several disorders, including malignancies, but its role is not well known. There are a group of inherited diseases affecting elastic fibres e.g. Marfan syndrome. It seems, that elastin degradation plays an important role in pathogenesis of some cardiovascular and pulmonary diseases. An enhanced elastolytic activity in malignancies is also observed. The data are rather sparse and above all concern lung and breast cancer. A trial estimating the role of elastin turnover in patients with hematologic malignancies, who underwent bone marrow transplantation, is now conducting in our department and preliminary results are promising.

Topics: Autoimmune Diseases; Cardiovascular Diseases; Elastic Tissue; Elastin; Humans; Lung Diseases; Neoplasms; Peptide Fragments; Receptors, Laminin; Risk Factors

D-Penicillamine, a heavy metal chelator used in the treatment of Wilson's disease and other conditions, may be associated with both noncutaneous and cutaneous side effects. Some of the cutaneous lesions are due to a toxic-metabolic effect on connective tissue; some may be explained on the basis of autoimmunity; some are acute sensitivity reactions, and some are secondary to unknown mechanisms. The types of cutaneous manifestations may, in some instances, be correlated with the disease being treated and the dosage and duration of penicillamine therapy.

Topics: Autoimmune Diseases; Collagen; Dermatitis, Atopic; Drug Eruptions; Elastin; Humans; Lichen Planus; Penicillamine; Skin; Stomatitis, Aphthous

Topics: Autoantigens; Autoimmune Diseases; Collagen; Elastin; Eye Proteins; Glycosaminoglycans; Humans; Inflammation; Lens Diseases; Lens, Crystalline

Topics: Aging; Allergy and Immunology; Antibody Formation; Arteriosclerosis; Autoantibodies; Autoimmune Diseases; Cell Membrane; Collagen; Connective Tissue; Corneal Transplantation; Elastin; Genes; Glycoproteins; Glycosaminoglycans; Histocompatibility Antigens; Humans; Mononuclear Phagocyte System; Solubility; Transplantation, Homologous

Topics: Animals; Antigens; Autoantibodies; Autoimmune Diseases; Collagen; Collagen Diseases; Elastin; Gelatin; Humans; Isoantibodies; Peptides; Reticulin; Species Specificity

The autoimmune disorder, Sjögren's syndrome (SS), is characterized by lymphocytic infiltration and loss of function of exocrine glands such as the lacrimal gland (LG) and salivary gland. SS-associated changes in the LG are associated with the development of autoimmune-mediated dry eye disease. We have previously reported the accumulation of intercellular adhesion molecule 1 (ICAM-1) in the LG of Non-Obese Diabetic (NOD) mice, a murine model of autoimmune-mediated dry eye in SS, in both LG acinar cells and infiltrating lymphocytes. ICAM-1 initiates T-cell activation and can trigger T-cell migration through binding to lymphocyte function-associated 1 antigen (LFA). To modulate this interaction, this study introduces a new tool, a multivalent biopolymeric nanoparticle assembled from a diblock elastin-like polypeptide (ELP) using the S48I48 (SI) ELP scaffold fused with a mouse ICAM-1 targeting peptide to form IBP-SI. IBP-SI forms a multivalent, monodisperse nanoparticle with a radius of 21.9 nm. Unlike the parent SI, IBP-SI binds mouse ICAM-1 and is internalized by endocytosis into transfected HeLa cells before it accumulates in lysosomes. In vitro assays measuring lymphocyte adhesion to Tumor Necrosis Factor TNF-α-treated bEnd.3 cells, which express high levels of ICAM-1, show that adhesion is inhibited by IBP-SI but not by SI, with IC

Topics: Animals; Autoimmune Diseases; Biopolymers; Cell Proliferation; Dry Eye Syndromes; Elastin; Endocytosis; HeLa Cells; Humans; Inflammation; Inhibitory Concentration 50; Intercellular Adhesion Molecule-1; Lacrimal Apparatus; Lymphocyte Function-Associated Antigen-1; Lymphocytes; Lysosomes; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred NOD; Nanoparticles; Peptides; Sjogren's Syndrome; T-Lymphocytes; Tumor Necrosis Factor-alpha

Liberation of elastin peptides from damaged lung may be a mechanism of autoimmune lung disease. Citrullination, and anti-citrullinated protein antibody formation occurs in smokers, but the role of smoking in autoantibody generation relevant to pulmonary disease is unclear. Anti-elastin, anti-cyclic citrullinated peptide (anti-CCP) and anti-mutated citrullinated vimentin (anti-MCV) antibodies were measured in 257 subjects with α₁-antitrypsin deficiency (AATD), 113 subjects with usual chronic obstructive pulmonary disease (COPD) and 22 healthy nonsmokers. Levels were compared between groups, against phenotypic features and against smoke exposure. Anti-elastin antibodies were higher in controls relative to AATD (p = 0.008) and usual COPD (p < 0.00001), and in AATD relative to usual COPD (p < 0.00001). Anti-elastin levels showed a threshold at 10 pack-yrs, being higher in those who had smoked less (p = 0.004). No relationships between antibody levels and clinical phenotype were seen after adjustment for smoke exposure. Anti-CCP antibodies were higher in usual COPD than AATD (p = 0.002) but the relationship to smoke exposure was less clear. Smoke exposure is the main determinant of anti-elastin antibody levels, which fall after 10 pack-yrs. Local antibody complexes may be a better measure of elastin directed autoimmunity than circulating levels.

Topics: Adult; Aged; alpha 1-Antitrypsin Deficiency; Autoimmune Diseases; Elastin; Female; Forced Expiratory Volume; Humans; Lung Diseases; Male; Middle Aged; Phenotype; Pulmonary Disease, Chronic Obstructive; Risk; Smoking; Time Factors

In patients with chronic inflammatory lung disease, pulmonary proteases can generate neoantigens from elastin and collagen with the potential to fuel autoreactive immune responses. Antielastin peptide antibodies have been implicated in the pathogenesis of tobacco-smoke-induced emphysema. Collagen-derived peptides may also play a role.. To determine whether autoantibodies directed against elastin- and collagen-derived peptides are present in plasma from three groups of patients with chronic inflammatory lung disease compared with a nonsmoking healthy control group and to identify whether autoimmune responses to these peptides may be an important component of the disease process in these patients.. A total of 124 patients or healthy control subjects were recruited for the study (Z-A1AT deficiency, n = 20; cystic fibrosis, n = 40; chronic obstructive pulmonary disease, n = 31; healthy control, n = 33). C-reactive protein, IL-32, and antinuclear antibodies were quantified. Antielastin and anti-N-acetylated-proline-glycine-proline autoantibodies were measured by reverse ELISA.. All patients were deemed stable and noninfective on the basis of the absence of clinical or radiographic evidence of recent infection. There were no significant differences in the levels of autoantibodies or IL-32 in the patients groups compared with the healthy control subjects.. Antielastin or anti-N-acetylated proline-glycine-proline autoantibodies are not evident in chronic inflammatory lung disease.

Topics: Adolescent; Adult; Aged; alpha 1-Antitrypsin Deficiency; Autoantibodies; Autoimmune Diseases; Case-Control Studies; Cystic Fibrosis; Elastin; Female; Humans; Male; Middle Aged; Oligopeptides; Pulmonary Disease, Chronic Obstructive; Smoking; Young Adult

The humoral immune response against elastin and collagen was studied in parallel with the delayed type hypersensitivity (DTH) reaction to elastin and the percentage of lymphocyte subpopulations in peripheral blood in 20 patients with systemic sclerosis (SSc). An increase of anti-elastin antibodies of all subclasses was found with a significant prevalence of IgE and IgA antibodies. The profile of anti-collagen type I and type IV antibodies showed an increase of IgE isotypes. In 25% of the patients (5 out of 20) positive DTH reactions to elastin were observed as compared to the negative skin reactions in all control individuals. At the same time a significant hyporeactivity to common bacterial and mould antigens was found in 40% of the patients (versus 16% in the control group) which could be an explanation for the low incidence of positive anti-elastin DTH reaction. The DTH hyporeactivity in SSc cases was in contrast with the increased percentage of CD4 T cells (58.4 vs. 42.0) and increased CD4/CD8 ratio (2.5 vs. 1.5) in the peripheral blood of the patients. This finding together with the increased IgE antibodies to elastin and collagen type I and type IV might suggest a possible shift of the immune balance towards the Th2 type of immune response. This is in line with the increased CD8+CD57+ cells which correlated with the highest number of other parameters studied - disease duration, total skin score, IgE anti-elastin antibodies, IgG anti-collagen type I antibodies, CD4/CD8 ratio and CD19 B cells. The results of this study demonstrated the existence of both humoral and cell-mediated immune response against elastin in SSc patients. However, we could not define whether this was an essential part of pathogenetic mechanisms or a secondary phenomenon reflecting the extent of the damage of connective tissue.

Topics: Adult; Aged; Antibody Formation; Antibody Specificity; Antigens, CD19; Autoantibodies; Autoantigens; Autoimmune Diseases; B-Lymphocyte Subsets; CD4-CD8 Ratio; CD4-Positive T-Lymphocytes; CD57 Antigens; CD8-Positive T-Lymphocytes; Collagen; Elastin; Female; Humans; Hypersensitivity, Delayed; Immunity, Cellular; Immunoglobulin Isotypes; Immunophenotyping; Lymphocyte Subsets; Middle Aged; Scleroderma, Systemic; Skin Tests

The cause of Peyronie's disease is unknown. Immunological mechanisms in the pathogenesis have been previously suggested. Antibodies to elastin are present in all individuals. However, abnormal serum levels of anti-tropoelastin (reflecting elastin synthesis) and anti-alpha-elastin (reflecting elastin destruction) are seen in a variety of autoimmune diseases. We show that patients with Peyronie's disease have higher levels of antibodies to tropoelastin (p < 0.047) and alpha-elastin (p < 0.012) than age-matched controls, suggesting an increase in elastin synthesis and breakdown, respectively. These findings suggest the presence of autoimmune mechanisms in the pathogenesis of Peyronie's disease, which may have future diagnostic and therapeutic implications.

Topics: Antibodies; Autoimmune Diseases; Collagen; Elastin; Enzyme-Linked Immunosorbent Assay; Humans; Male; Penile Induration; Tropoelastin

Dermatitis herpetiformis (DH), is associated with skin eruptions and granular depositions of IgA in the papillary dermis, but this is not a feature of coeliac disease (CD). The specificity of the IgA in the skin is unknown. High molecular weight glutenin (HMW-g), a component of gluten, has been shown to have structural similarities to human elastin. This paper reports immunoadsorption studies which suggest that human serum may contain antibodies which cross-react with HMW-g and elastin. DH patients had significantly lower levels of IgA antibodies to HMW-g and to elastin than both CD patients and healthy controls. Furthermore, introduction of a gluten-free diet (GFD) was associated with a further reduction in the amount of IgA antibodies to elastin in the DH patients. This diet-associated decrease of elastin antibodies was restricted to the IgA isotype. A significant correlation was observed between IgA antibodies to HMW-g and elastin in healthy controls and CD patients, while no such correlation was found in patients with DH. These findings could indicate that HMW-g induces production of antibodies to elastin, which are deposited in the skin, and that when the antigenic stimulus is removed, these antibodies are further reduced due to continuous dermal deposition. It is postulated that DH may be an autoimmune disease due to cross-reactivity between dietary glutenin and dermal elastin.

Topics: Adult; Autoantibodies; Autoimmune Diseases; Celiac Disease; Cross Reactions; Dermatitis Herpetiformis; Diet; Elastin; Enzyme-Linked Immunosorbent Assay; Glutens; Humans; Immunoglobulin A; Immunoglobulin G; Middle Aged; Skin; Triticum

Topics: Animals; Antigens; Arteries; Arteriosclerosis; Autoantibodies; Autoimmune Diseases; Elastin; Fluorescent Antibody Technique; Lipids; Rabbits

Topics: Animals; Aorta; Arteriosclerosis; Autoimmune Diseases; Elastic Tissue; Elastin; Proteins; Rabbits; Swine