thromboplastin and Leprosy

Leprosy is a chronic infectious disease that requires better understanding since it continues to be a significant health problem in many parts of the world. Leprosy reactions are acute inflammatory episodes regarded as the central etiology of nerve damage in the disease. The activation of endothelium is a relevant phenomenon to be investigated in leprosy reactions. The present study evaluated the expression of endothelial factors in skin lesions and serum samples of leprosy patients. Immunohistochemical analysis of skin samples and serum measurements of VCAM-1, VEGF, tissue factor and thrombomodulin were performed in 77 leprosy patients and 12 controls. We observed significant increase of VCAM-1 circulating levels in non-reactional leprosy (p = 0.0009). The immunostaining of VEGF and tissue factor was higher in endothelium of non-reactional leprosy (p = 0.02 for both) than healthy controls. Patients with type 1 reaction presented increased thrombomodulin serum levels, compared with non-reactional leprosy (p = 0.02). In type 2 reaction, no significant modifications were observed for the endothelial factors investigated. The anti-inflammatory and antimicrobial activities of the endotfhelial factors may play key-roles in the pathogenesis of leprosy and should be enrolled in studies focusing on alternative targets to improve the management of leprosy and its reactions.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Child; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunohistochemistry; Leprosy; Male; Middle Aged; Skin; Thrombomodulin; Thromboplastin; Vascular Cell Adhesion Molecule-1; Vascular Endothelial Growth Factor A; Young Adult

The antiphospholipid syndrome (APS) is characterized by the presence of antiphospholipid antibodies (aPL) in patients with thromboembolic complications. In APS, most aPL are autoantibodies to beta2-glycoprotein I and prothrombin, which play a major role in the APS pathogenesis. Nevertheless, antibodies with the same antigen specificity are also found in aPL patients with leprosy, in whom thromboembolic complications are uncommon. The in vivo upregulation of the tissue factor (TF) pathway and the imbalance of cytokines have been proposed as potential mechanisms of thrombosis in the APS. We measured the circulating levels of TF, interleukin 6 (IL-6), IL-6 receptor (sIL-6R), tumor necrosis factor (TNF-alpha) and interferon gamma (IFN-gamma) in 83 patients with autoimmune aPL (42 with and 41 without clinical features of definite primary APS), 48 leprosy patients (33 with aPL) and 48 normal controls. There was a trend (P = 0.06) to higher median sTF in patients with autoimmune aPL (139 pg/mL) compared with leprosy patients (103.5 pg/mL) and controls (123 pg/mL). In addition, the frequency of raised sTF levels (> 187 pg/mL) was significantly higher in the group with autoimmune aPL [22.9% (APS 21.4%, non-APS 24.4%)] but not in leprosy (10.4%) compared with controls (4.2%). Elevated levels of IL-6 and TNF-alpha and a trend to lower IFN-gamma were found in patients with definite APS. Leprosy patients with aPL, however, had increased TNF-alpha and IFN-gamma but normal IL-6 levels. Levels of sIL-6R did not differ between controls and either patients with autoimmune aPL or leprosy. The different cytokine profiles as well as differences in circulating levels of TF might contribute to the high thrombotic risk found in patients with autoimmune aPL but not in leprosy related aPL patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Child; Female; Humans; Interferon-gamma; Interleukin-6; Leprosy; Male; Middle Aged; Receptors, Interleukin-6; Thromboplastin; Tumor Necrosis Factor-alpha

We observed a patient with lepromatous leprosy and a circulating anticoagulant. Intrinsic pathway inhibition was demonstrated by prolongation of the activated partial thromboplastin time. Extrinsic pathway inhibition was demonstrated by prolongation of the prothrombin time when performed with diluted thromboplastin. A plasma co-factor was required for inhibition. Immunoadsorption with specific antisera and Sephadex G-200 fractionation suggested that the anticoagulant was an IgM immunoglobulin. The similarities between this patient's anticoagulant and those associated with other disease states are discussed.

Topics: Adult; Blood Coagulation; Chromatography, Gel; Humans; Immunosorbent Techniques; Leprosy; Male; Prothrombin Time; Thrombin; Thromboplastin