A Clue for Telangiectasis in Systemic Sclerosis: Elevated Serum Soluble Endoglin Levels in Patients with the Limited Cutaneous Form of the Disease

Abstract

Background: The transforming growth factor-β (TGF-β) system plays a critical role both in systemic sclerosis (SSc) and hereditary hemorrhagic telangiectasia (HHT). Endoglin, known as a gene responsible for HHT, is a TGF-β receptor preferentially expressed on endothelial cells. The role of endoglin in SSc is potentially intriguing since limited cutaneous SSc (lcSSc) and HHT share several symptoms, including telangiectasia. Objective: To determine serum levels of soluble endoglin (sEndoglin) and clinical associations in patients with SSc. Methods: Serum sEndoglin levels were examined by ELISA in 70 patients with SSc, 20 patients with systemic lupus erythematosus and 20 healthy individuals. Results: Serum sEndoglin levels were significantly elevated in patients with lcSSc compared with diffuse cutaneous SSc and systemic lupus erythematosus patients as well as normal controls. Patients with elevated sEndoglin levels had telangiectasia more frequently than those with normal sEndoglin levels. Furthermore, pulmonary artery pressure was positively correlated with sEndoglin levels in patients with lcSSc. Conclusion: Abnormal expression/function of endoglin may be linked to lcSSc-specific manifestations.

The physiological role of endoglin in the cardiovascular system

“…In addition to preeclampsia and brain AVMs, altered sEng levels have been reported in several pathologies such as cancer (13,26,99), atherosclerosis and coronary artery disease (16,102), hepatitis (34), diabetes (5), systemic sclerosis (44,58), malaria (45), biliary atresia (133), or sickle cell disease (86). Interestingly, a number of laboratories have reported increased levels of sEng in serum, plasma, or other fluids from cancer patients as a marker of poor prognosis [reviewed by Fonsatti et al (56) and Bernabeu et al (13)].…”

Pulmonary hypertension in systemic sclerosis and systemic lupus erythematosus

“…Patients with HHT demonstrate genetic mutations in the TGF-b receptor complex, most notably endoglin (a TGF-b binding protein) and activin receptor-like kinase 1. Telangiectasias are more frequently found in SSc patients with elevated soluble endoglin, and pulmonary artery pressure (Ppa) is positively correlated with elevated endoglin levels [25]. It is hypothesised that the presence of telangiectasia is an expression of an aberrant vascular process.…”

Generalized Telangiectasia: A Manifestation of Intravascular B-Cell Lymphoma

“…These are due to a reactive vascular proliferation to the thrombo-occlusive insult caused by the intravascular proliferation. To the best of our knowledge, generalized telangiectasia as a manifestation of IVL, as in our case, has been only described in 4 patients [3][4][5][6] .…”

“…The telangiectasias in systemic sclerosis, mainly the limited cutaneous systemic sclerosis, have recently been attributed to abnormally elevated levels of serum endoglin. This protein that functions as a TGF-␤ receptor is known to be mutated in hereditary hemorrhagic telangiectasia, an inherited disorder characterized by skin and visceral telangiectasias [6,7] .…”