title: Anti-thrombomodulin antibodies and venous thrombosis.
abstract: Thrombomodulin (TM) is a cell surface endothelial glycoprotein having anticoagulant properties. It inhibits thrombin, and activates protein C, leading to the inhibition of activated factors V and VIII. TM autoantibodies could theoretically predispose to thrombosis. We have tested 83 unselected patients with deep venous thrombosis, 36 males and 47 females aged from 1 to 70 years [mean +/- standard deviation (SD), 34.2 +/- 14.5 years] for the presence of IgG anti-TM in their plasmas. Tests were performed by enzyme-linked immunosorbent assay (ELISA) using recombinant human TM kindly provided by PAION GmbH (Aachen, Germany). Results are expressed as the optical density (OD) differences between coated and un-coated wells. Plasmas from 83 normal volunteer donors were used to define the cut-off value as the mean of absorbance of the control group + 3 SDs. The median OD of normal controls group was 0.024 (mean, 0.034; SD, 0.066; range, -0.048 to 0.309). The median OD obtained with plasmas from patients was 0.048 (mean, 0.114; SD, 0.215; range, -0.039 to 1.312) and was significantly higher than that of the control group (P < 0.0001). Choosing a cut-off value of 0.232 (mean OD of the control group + 3 SDs), 11 patients are considered as positive for IgG autoantibodies to TM and three normal controls are weakly positive. Selected plasma with IgG anti-TM and purified IgG were further tested by dot blot using recombinant purified TM and were found positive. Purified IgG of positive plasmas inhibits protein C activation by TM and thrombin, suggesting that anti-TM antibodies have a procoagulant effect. Interestingly, in our study, anti-TM antibodies are found in three of six patients with Budd-Chiari syndrome and four of eight patients with cerebral venous thrombosis. In conclusion, thrombomodulin autoantibodies could be a new interesting marker of thrombophilia easily detected by ELISA.
authors.affiliation: Laboratoire d'Hématologie, Institut Pasteur de Tunis, Tunis-Belvédère, Hôpital Charles Nicolle, Tunis, Tunisia. sami.guermazi@pasteur.rns.tn
authors.forename: Sami
authors.initials: S
authors.lastname: Guermazi
authors.forename: Fathi
authors.initials: F
authors.lastname: Mellouli
authors.forename: Senda
authors.initials: S
authors.lastname: Trabelsi
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bejaoui
authors.forename: Koussay
authors.initials: K
authors.lastname: Dellagi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology; D007223:Infant; D008297:Male; D008875:Middle Aged; D018180:Thrombomodulin / Q000276:immunology*; D020246:Venous Thrombosis / Q000097:blood* / Q000276:immunology / Q000473:pathology
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D018180:Thrombomodulin