C W Carson1, P C Comp, A R Rezaie, N L Esmon, C T Esmon. 1. Oklahoma Medical Research Foundation, Department of Medicine, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA.
Abstract
OBJECTIVE: To test the hypothesis that thrombomodulin (TM) may be a target for lupus anticoagulant (LAC) antibodies. METHODS: A recombinant soluble form of TM was produced and used as an antigen for an ELISA to detect antibodies to TM (TMAB). Sixty-one samples from 58 patients identified by the coagulation laboratory as having a LAC and 200 patients with unexplained thrombosis were evaluated along with 201 healthy controls. RESULTS: Eighteen (30%) of the 58 patients with a LAC and 20 (10%) of 200 patients with unexplained thrombosis had antibodies to TM. Similar antibodies were found in only 4 (2%) of 201 normal controls. TMAB show selectivity for TM lacking chondroitin sulfate, but do not otherwise have an immunodominant region. The IgG from 6 patients with TMAB was purified, and it bound TM in our ELISA. Three of the 6 IgG fractions inhibited protein C activation 40% to 70% compared to no inhibition in 7 healthy controls. CONCLUSION: Some patients with LAC and unexplained thrombosis have antibodies to TM that may arise in response to TM that has been altered and lost its chondroitin sulfate attachment. Antibodies to TM may be an important risk factor for inflammation and thrombosis in these patients.
OBJECTIVE: To test the hypothesis that thrombomodulin (TM) may be a target for lupus anticoagulant (LAC) antibodies. METHODS: A recombinant soluble form of TM was produced and used as an antigen for an ELISA to detect antibodies to TM (TMAB). Sixty-one samples from 58 patients identified by the coagulation laboratory as having a LAC and 200 patients with unexplained thrombosis were evaluated along with 201 healthy controls. RESULTS: Eighteen (30%) of the 58 patients with a LAC and 20 (10%) of 200 patients with unexplained thrombosis had antibodies to TM. Similar antibodies were found in only 4 (2%) of 201 normal controls. TMAB show selectivity for TM lacking chondroitin sulfate, but do not otherwise have an immunodominant region. The IgG from 6 patients with TMAB was purified, and it bound TM in our ELISA. Three of the 6 IgG fractions inhibited protein C activation 40% to 70% compared to no inhibition in 7 healthy controls. CONCLUSION: Some patients with LAC and unexplained thrombosis have antibodies to TM that may arise in response to TM that has been altered and lost its chondroitin sulfate attachment. Antibodies to TM may be an important risk factor for inflammation and thrombosis in these patients.
Authors: Xunzhen Zheng; Weihong Li; Jian-Ming Gu; Dongfeng Qu; Gary L Ferrell; Naomi L Esmon; Charles T Esmon Journal: Blood Date: 2006-10-05 Impact factor: 22.113