Background: Idiopathic carpal tunnel syndrome (ICTS) is a common entrapment neuropathy. Some cases of ICTS are linked to mutations in the transthyretin gene, while others are associated with systemic amyloidosis. The majority of ICTS cases are of unknown etiology.
Objective: To study molecular mechanisms of CTS development.
Methods: A total of 71 ICTS patients and 68 controls were included in the study. Fibrinogen level was determined prior to surgery and its deposition in transversal carpal ligament (TCL) was detected by immunohistochemistry, western blot and mass spectrometry. Fibrinogen interaction with other proteins was studied by immunoprecipitation assay.
Results: Plasma levels of the pro-inflammatory and haemostatic protein, fibrinogen, are elevated in ICTS patients. Other measured systemic inflammatory markers were not affected and local inflammatory responses in TCL were absent. ICTS patients have shorter bleeding times probably due to elevated plasma levels of fibrinogen. Polymorphisms of the fibrinogen B promoter region were previously associated with elevated plasma fibrinogen, but this association was not observed among patients with ICTS. Interestingly, we detected fibrinogen deposits in the TCL while transcriptional activity of the fibrinogen genes was low. Amyloidogenic proteins, including transthyretin and [alpha]-synuclein, were also found in the TCL while their local transcriptional activity was rather high. Finally, we demonstrated that fibrinogen interacts with transthyretin and [alpha]-synuclein in TCL lysates.
Conclusion: Our data indicate that fibrinogen and other aggregation-prone proteins have potentially important roles in the pathogenesis of ICTS.
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