chondroitin-sulfates and Lupus-Erythematosus--Systemic

Platelets participate in a variety of responses of the blood to injury. An emerging body of evidence suggests that these cells express an intrinsic capacity to interact with and trigger both classical and alternative pathways of complement. This activity requires cell activation with biochemical agonists and/or shear stress, and is associated with the expression of P-selectin, gC1qR, and chondroitin sulfate. Platelet mediated complement activation measurably increases soluble inflammatory mediators (C3a and C5a). Platelets may also serve as targets of classical complement activation in autoimmune conditions such as antiphospholipid syndromes (APS) and immune thrombocytopenia purpura (ITP). Retrospective correlation with clinical data suggests that enhanced platelet associated complement activation correlates with increased arterial thrombotic events in patients with lupus erythematosus and APS, and evidence of enhanced platelet clearance from the circulation in patients with ITP. Taken together, these data support a role for platelet mediated complement activation in vascular inflammation and thrombosis.

Topics: Animals; Antiphospholipid Syndrome; Blood Platelets; Carrier Proteins; Chondroitin Sulfates; Complement Activation; Complement C3a; Complement C5a; Humans; Inflammation Mediators; Lupus Erythematosus, Systemic; Mitochondrial Proteins; P-Selectin; Purpura, Thrombocytopenic, Idiopathic; Thrombosis; Vasculitis

Patients with malignancy often present with a variety of coagulation abnormalities which may ultimately lead to recurrent arterial and venous thromboses. Recently the presence of antiphospholipid antibodies in cancer patients has been proposed as one of the potential mechanisms promoting hypercoagulability. Here we report two consecutive patients with localized tumors, one suffering from breast cancer and another presenting with colorectal cancer, who experienced dramatic exacerbation of the antiphospholipid antibody syndrome (APAS) within 4 weeks after surgery. In the first patient who had also received one course of adjuvant chemotherapy, major ischemic stroke and recurrent venous thromboembolism were paralleled by the development of ulcerative livedoid vasculitis and pancytopenia, constituting the diagnosis of systemic lupus erythematosus with secondary APAS. In the second patient, progressive thrombotic occlusion of the superior and inferior vena cava was associated with bilateral pulmonary embolism, acute renal failure, and disabling soft tissue edema. Although not fulfilling the classic criteria of "catastrophic" APAS, the clinical features were life threatening and appeared to be refractory to oral anticoagulation with phenprocoumon. In addition, a diagnosis of Trousseau's syndrome was unlikely due to missing evidence of gross metastatic disease. Besides a suggested treatment strategy comprising high doses of low-molecular-weight heparin, potential pathogenic mechanisms are discussed in consideration of a recently proposed "thrombotic storm," which may cause multiple thromboses after an initial provocation in patients with known hypercoagulability.

Topics: Adult; Antiphospholipid Syndrome; Breast Neoplasms; Chemotherapy, Adjuvant; Chondroitin Sulfates; Colorectal Neoplasms; Dermatan Sulfate; Drug Combinations; Female; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Lupus Erythematosus, Systemic; Middle Aged; Neoplasms; Stroke; Thromboembolism; Thrombophilia

The mechanism for the production of papulonodular mucinosis in patients with lupus erythematosus (LE) is not known.. Our purpose was to determine whether fibroblasts in a patient with LE and papulonodular mucinosis produced more mucin than normal fibroblasts and whether this mucin production could be stimulated by the patient's serum.. Skin fibroblasts from a patient with systemic LE and massive papulonodular mucin deposition, as well as normal fibroblasts, were incubated in the presence of serum from the patient or from a healthy volunteer. The production of glycosaminoglycan by fibroblasts was analyzed.. Fibroblasts from the patient produced more glycosaminoglycan than did normal fibroblasts. Glycosaminoglycan production was increased in all cells when incubated in the presence of the patient's serum.. Cutaneous mucin deposition in patients with papulonodular LE skin lesions is associated with increased glycosaminoglycan production by dermal fibroblasts. Our preliminary observations suggest glycosaminoglycan production by these fibroblasts appears to be stimulated by a factor, (or factors) in the patient's serum that is yet to be identified.

Topics: Adult; Cells, Cultured; Chondroitin Sulfates; Fibroblasts; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Keratinocytes; Lupus Erythematosus, Systemic; Male; Mucinoses; Mucins; Skin; Up-Regulation

Systemic lupus erythematosus (SLE) is an autoimmune disease which involves the basement membranes of blood vessels in multiple organs. An important component of the microvasculature is vascular heparan sulfate proteoglycan (HSPG). In this study, we investigated the presence in SLE and other immune disease sera of autoantibodies to purified vascular HSPG. Our data demonstrate that antibody to HSPG is found primarily in SLE sera, and not in sera from controls or patients with other immune diseases. The titer of antibody to HSPG correlated with complement depletion in SLE sera. Antibody to HSPG was frequently found in high titer in SLE patients with renal and neurologic involvement. These studies indicate that our assay for antibody to vascular HSPG detects a pathologically relevant autoantibody in SLE sera. The implications of our findings for pathogenesis of vascular autoimmunity are discussed, including the relationship of anti-vascular HSPG antibody to anti-DNA and antiphospholipid antibodies.

Topics: Administration, Topical; Anti-Inflammatory Agents; Antibody Specificity; Arthritis, Rheumatoid; Basement Membrane; Blotting, Western; Chondroitin Sulfates; Collagen; Complement System Proteins; Dose-Response Relationship, Immunologic; Enzyme-Linked Immunosorbent Assay; Fibronectins; Heparin; Heparitin Sulfate; Humans; Hyaluronic Acid; Laminin; Lupus Erythematosus, Systemic; Muscle, Smooth, Vascular; Polymyalgia Rheumatica; Proteoglycans; Scleroderma, Systemic; Sjogren's Syndrome

Topics: Adolescent; Biomedical Research; Chloroquine; Chondroitin; Chondroitin Sulfates; Drug Therapy; Lupus Erythematosus, Discoid; Lupus Erythematosus, Systemic; Placebos; Tablets