Showing papers by "Antonella Capozzi published in 2009"

Biochemistry and neurobiology of prosaposin: a potential therapeutic neuro-effector

Abstract: Prosaposin, a 66 kDa glycoprotein, was identified initially as the precursor of the sphingolipid activator proteins, saposins A-D, which are required for the enzymatic hydrolysis of certain sphingolipids by lysosomal hydrolases. While mature saposins are distributed to lysosomes, prosaposin exists in secretory body fluids and plasma membranes. In addition to its role as the precursor, prosaposin shows a variety of neurotrophic and myelinotrophic activities through a receptor-mediated mechanism. In studies in vivo, prosaposin was demonstrated to exert a variety of neuro-efficacies capable of preventing neuro-degeneration following neuro-injury and promoting the amelioration of allodynia and hyperalgesia in pain models. Collective findings indicate that prosaposin is not a simple house-keeping precursor protein; instead, it is a protein essentially required for the development and maintenance of the central and peripheral nervous systems. Accumulating evidence over the last decade has attracted interests in exploring and developing new therapeutic approaches using prosaposin for human disorders associated with neuro-degeneration. In this review we detail the structure characteristics, cell biological feature, in vivo efficacy, and neuro-therapeutic potential of prosaposin, thereby providing future prospective in clinical application of this multifunctional protein.

Association of anti-C1 inhibitor and anti-protein S antibodies in a patient with primary antiphospholipid syndrome.

Abstract: Dear Editor, We would like to report the existence of a previously nondescribed association of anti-protein S and anti-C1 inhibitor antibodies in a patient with primary antiphospholipid syndrome (PAPS). A 73-year-old Caucasian woman was referred from the internal medicine unit for evaluation of the hypocomplementemic state. She was previously diagnosed as having PAPS according to Sapporo revised criteria.1 She had a cerebrovascular event in November 2006, and multiple ischemic lesions in the brain were observed in an magnetic resonance imaging study. High titres of anticardiolipin (IgM class >80 MPL, sometimes low levels of IgG class) and antiprothrombin antibodies were detected by enzyme-linked immunosorbent assay (ELISA). Lupus anticoagulant was confirmed according to recommendations of the Subcommittee on Lupus Anticoagulant/Phospholipid-dependent Antibodies.2 No clinical manifestations suggesting systemic lupus erythematosus were present, and antinuclear antibodies were negative. The patient did not show clinical manifestations of hereditary angioedema. All biochemical parameters tested were within the normal range. Coagulation studies showed evidence of low protein S levels: 18% (normal range: 60–125). Complement studies showed nearly normal C3 levels: 76.1 mg/dL (normal range: 77–135) and very low complement C4: 1.43 mg/dL (normal range: 14–60). C1 inhibitor levels were not detectable (<2.8 mg/dL), andC1q level was <11.5 μg/mL, revealing a complement profile similar to that described in patients with acquired angioedema (anti-C1q antibodies were negative). Anti-C1 inhibitor3 antibodies (IgG class 1:200) and anti-protein S4 antibodies (IgG and IgM classes 1:800) were detected by ELISA. Monoclonal component was not detected in her serum. We have the first evidence of an association between anti-C1 inhibitor and anti-protein S autoantibodies. In previous articles, the presence of anti-protein S antibodies in patients with acquired protein S deficiency was demonstrated.5–7 Moreover, we observed the presence of anti-C1 inhibitor antibodies with a consequent low level of C1 inhibitor. The relationship between anti-protein S and antiC1 inhibitor antibodies is unknown. It is possible that a pathogen with an important activation of both coagulation and the complement system caused this association. The complement cascade is activated by the same stimuli that launch inflammation, for example, when the danger of infection is detected or the host tissue is damaged.8 In most pathophysiological situations, it seems that the activation of both the complement and coagulation cascades occurs simultaneously. Lately, Széplaki, et al.9 have described acquired angioedema in a patient with PAPS and antithrombin III deficiency, but the presence of antithrombin III autoantibodies was not tested. C1 inhibitor deficiency is the main cause of both hereditary and acquired angioedema. Clinical manifestations associated with C1 inhibitor deficiency are highly variable; they range from absence of symptoms to life-threatening episodes such as glottis attacks. Recently, Blanch, et al.10 have described a family with two members homozygous for C1 inhibitor deficiency. To date, one of them has not had clinical manifestations of angioedema. These facts suggest that additional factors are involved in clinical manifestations of angioedema. From a practical point of view, we can conclude that patients with anti-C1 inhibitor antibodies with consequent low level of C1 inhibitor must be accurately monitored for coagulation parameters, including protein S activity.