Serum levels of soluble programmed death‐1 and programmed death ligand‐1 in systemic sclerosis: Association with extent of skin sclerosis

The interaction of programmed death‐1 (PD‐1) with its ligand, programmed death ligand‐1 (PD‐L1), has been considered to play a key role in the negative regulation of immune responses. Patients with diffuse cutaneous systemic sclerosis (SSc) had higher levels of soluble PD‐1 (sPD‐1) than those with limited cutaneous SSc and healthy individuals. Serum sPD‐1 levels positively correlated with the severity of skin sclerosis. In contrast, serum sPD‐L1 levels were significantly increased in patients with SSc compared with healthy individuals. Moreover, serum sPD‐L1 levels were not associated with the extent of skin sclerosis and were elevated not only in patients with diffuse cutaneous SSc, but also in those with limited cutaneous SSc. These results suggested that serum sPD‐1 levels may increase in patients with SSc and correlate with the severity of skin sclerosis. PD‐1/PD‐L1 interaction may contribute to the development of skin sclerosis in SSc.     

Possible association of elevated serum collagen type IV level with skin sclerosis in systemic sclerosis

Collagen type IV is the primary collagen in the basement membranes around blood vessels and in the dermoepidermal junction in the skin. Perivascular collagen type IV is synthesized by endothelial cells and pericytes, and contributes to the homeostasis and remodeling of blood vessels. It has been well recognized that elevated serum collagen type IV levels are associated with the liver fibrosis. The objective was to examine serum collagen type IV levels and their clinical associations in patients with systemic sclerosis (SSc), and to examine the expression of collagen type IV in the fibrotic skin in SSc. Serum collagen type IV levels in SSc patients and diffuse cutaneous type SSc patients were significantly higher than those in healthy individuals. Serum collagen type IV levels were positively correlated with modified Rodnan total skin score. Serum collagen type IV levels in early stage (disease duration ≤3 years) diffuse cutaneous SSc patients were significantly elevated. Serum collagen type IV levels in SSc patients with digital ulcers (DU) were significantly elevated. In immunohistochemical staining, the expression of collagen type IV around dermal small vessels in the affected skin was reduced compared with those of normal individuals. These results suggest that elevated serum collagen type IV levels may be associated with the skin sclerosis in the early stage of SSc. The measurement of serum collagen type IV levels in SSc patients may be useful as a disease activity marker in skin sclerosis and DU.     

Interleukin (IL)-17F and IL-17E are related to fibrosis and vasculopathy in systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disease that causes fibrosis and vasculopathy of the skin and internal organs against a background of autoimmune abnormalities. In recent years, the importance of the interleukin (IL)-17 family for inflammatory diseases has received much attention, but autoimmune diseases have not yet been fully explored. As for SSc, there is also no unified perspective on the involvement of the IL-17 family in its development, and few studies have been conducted linking IL-17F and IL-17E particularly to the disease severity. In the present study, we examined the correlation between serum IL-17F and IL-17E levels and disease severity in SSc patients. Moreover, the expression of the receptors for these cytokines, IL-17RB and IL-17RC, in skin tissues obtained by skin biopsy was examined by immunohistochemistry. Both cytokines were significantly elevated in the sera of patients with diffuse cutaneous SSc patients compared with healthy controls. Serum IL-17F levels correlated with modified Rodnan total skin thickness score, a semiquantitative measure of skin sclerosis, percent predicted forced vital capacity, percent predicted carbon monoxide lung diffusion capacity and serum levels of Krebs von den Lungen-6 and surfactant protein-D, serological markers of interstitial lung disease. Serum IL-17E levels were significantly correlated with percent predicted forced vital capacity and serum Krebs von den Lungen-6 levels. Serum levels of IL-17F and IL-17E also correlated with the prevalence of digital ulcers, and serum IL-17F levels were associated with elevated right ventricle systolic pressure values. In addition, IL-17RC and IL-17RB expression was increased in the skin tissues of diffuse cutaneous SSc patients. These results suggested that IL-17F and IL-17E could be involved in fibrosis and vasculopathy in SSc through their respective receptors in the affected organ tissues.     

Augmented production of soluble CD93 in patients with systemic sclerosis and clinical association with severity of skin sclerosis

Background The cell surface protein CD93, expressed on endothelial and myeloid cells, mediates phagocytosis, inflammation and cell adhesion. A soluble form of CD93 (sCD93) is released during inflammation. Objectives To determine the serum sCD93 level and its association with clinical parameters in patients with systemic sclerosis (SSc). Methods Serum sCD93 levels were examined by enzyme‐linked immunosorbent assay in 59 patients with SSc, 24 patients with systemic lupus erythematosus and 47 healthy individuals. The expression of CD93 in skin tissues was examined immunohistochemically. In a retrospective longitudinal study, sera from 11 patients with SSc were analysed. Results Serum sCD93 levels were increased in patients with SSc compared with healthy individuals (P < 0·001). Patients with diffuse cutaneous SSc showed greater levels of sCD93 than those with limited cutaneous SSc (P < 0·01) or systemic lupus erythematosus (P < 0·01). Serum sCD93 levels correlated positively with the severity of skin sclerosis. Strong CD93 immunostaining was observed on endothelial cells in lesional skin tissues. In the longitudinal study, sCD93 levels decreased in parallel with improvement in skin sclerosis. Conclusions Serum sCD93 levels are increased in patients with SSc and correlate with the severity and activity of skin sclerosis. CD93 may contribute to the development of skin fibrosis in SSc.     

Serum periostin levels are correlated with progressive skin sclerosis in patients with systemic sclerosis

Background Periostin, a matricellular protein, serves as a regulator of wound healing and fibrosis. The role of periostin in the pathogenesis of systemic sclerosis (SSc) is unknown. Objective To determine periostin levels in association with severity of skin fibrosis in patients with SSc. Methods Expression of periostin was immunohistochemically examined in skin obtained from patients with SSc and healthy controls. Enzyme‐linked immunosorbent assay was performed to evaluate serum periostin levels in association with clinical characteristics in 56 patients with SSc [diffuse cutaneous SSc (dSSc), n = 16; and limited cutaneous SSc (lSSc), n = 40] and 66 healthy controls. Results Periostin was strongly expressed in the affected dermis from patients with SSc. Periostin was colocalized in α‐smooth muscle actin‐positive myofibroblasts and platelet endothelial cell adhesion molecule‐1‐positive endothelial cells in SSc dermis. Serum levels of periostin in patients with dSSc were markedly elevated compared with those in patients with lSSc and control subjects. Patients with lSSc had increased periostin levels compared with healthy controls. In addition, significantly higher levels of periostin were observed in patients with dSSc with disease duration ≤ 5 years compared with those with disease duration > 5 years. Furthermore, the modified Rodnan total skin thickness score (MRSS) was positively correlated with periostin levels in patients with SSc. Serial analysis revealed a correlation between periostin and MRSS; namely, MRSS decreased in line with decreased periostin levels in some patients with dSSc as the disease progressed. Conclusion An elevated periostin level in patients with SSc is associated with severity of skin sclerosis. Periostin may be a potential biomarker for progressive skin fibrosis in SSc.     

Elevated serum KL-6 levels in patients with systemic sclerosis: association with the severity of pulmonary fibrosis

BACKGROUND: Serum KL-6 has been suggested to be a useful marker for the evaluation of interstitial lung disease activity. OBJECTIVE: To determine the correlation between serum KL-6 levels and pulmonary fibrosis in patients with systemic sclerosis (SSc). METHODS: Serum samples from patients with limited cutaneous SSc (lSSc; n = 19), diffuse cutaneous SSc (dSSc; n = 26) and normal individuals (n = 15) were examined by ELISA. RESULTS: Serum KL-6 levels in SSc patients were significantly higher than those in normal controls. KL-6 levels in dSSc patients were significantly elevated compared with those in lSSc patients. Elevated KL-6 levels were associated with the presence of pulmonary fibrosis in SSc patients or dSSc patients. Furthermore, KL-6 levels inversely correlated with percentages of diffusion capacity of carbon monoxide and vital capacity in SSc patients or dSSc patients. CONCLUSION: KL-6 may be a simple, serologic indicator for the severity of pulmonary fibrosis in SSc.     

Increased production of soluble inducible costimulator in patients with diffuse cutaneous systemic sclerosis

Inducible costimulator (ICOS) is crucial for T cell proliferation, production of various cytokines, and T cell-dependent B-cell responses. To determine the serum soluble ICOS (sICOS) level and its association with clinical parameters in patients with systemic sclerosis (SSc), serum sICOS level was examined by enzyme-linked immunosorbent assay in 38 patients with SSc and 24 healthy individuals. The expression of ICOS and ICOS ligand in skin was examined immunohistochemically. There was no significant difference in serum sICOS level between patients with SSc and healthy individuals. Patients with diffuse cutaneous SSc had higher levels of sICOS than those with limited cutaneous SSc (P < 0.05) or healthy individuals (P < 0.05). Serum sICOS level correlated positively with the severity of skin sclerosis. Patients with SSc and elevated sICOS level more often had interstitial lung disease and decreased vital capacity than those with normal sICOS level. The serum sICOS level was significantly greater in patients with early phase SSc than those with late phase SSc. ICOS and ICOS ligand immunostaining were observed on infiltrating dermal mononuclear cells in lesional skin tissue. These results suggest that the serum level of sICOS is increased in patients with diffuse cutaneous SSc and correlates with the severity and activity of skin sclerosis and interstitial lung disease. ICOS may contribute to the development of SSc. In addition, measurement of serum sICOS level in patients with early SSc may offer an important means for further evaluation of SSc disease severity.     

Clinical significance of serum decoy receptor 3 levels in patients with systemic sclerosis

Decoy receptor 3 (DcR3) is associated with autoimmunity and altered angiogenesis in certain pathological conditions. We herein measured serum DcR3 levels in 51 patients with systemic sclerosis (SSc) and 19 healthy controls and evaluated their clinical significance in this disorder. Serum DcR3 levels were significantly higher in diffuse cutaneous SSc (dcSSc) patients than in limited cutaneous SSc patients and in healthy controls. In dcSSc, serum DcR3 levels were significantly elevated in patients with disease duration of ≤6?years compared with healthy controls, but not in those with disease duration of >6?years. Serum DcR3 levels correlated negatively with the percentage of predicted diffusion lung capacity for carbon monoxide and positively with right ventricular systolic pressure. Furthermore, serum DcR3 levels positively correlated with C-reactive protein, erythrocyte sedimentation rate and immunoglobulin G. Collectively, the elevation of serum DcR3 levels is associated with the development of pulmonary arterial hypertension and systemic inflammation in SSc.     

Serum levels of soluble vascular endothelial growth factor receptor‐2 in patients with systemic sclerosis

Background Although vascular endothelial growth factor (VEGF)‐A/VEGF receptor 2 (KDR) signalling may play a major role in the microangiopathy of systemic sclerosis (SSc), serum levels of soluble KDR (sKDR) in this disease have not yet been determined. Objectives To evaluate the possibility that serum sKDR levels can be a specific disease marker of SSc. Methods Serum sKDR levels of 42 patients with SSc, 10 patients with Raynaud’s phenomenon (RP) and 22 healthy controls were measured with specific enzyme‐linked immunosorbent assays. Quantitative real‐time polymerase chain reaction (PCR) was performed to determine KDR mRNA levels. Results In females, the serum sKDR levels were significantly higher in patients with SSc, especially limited cutaneous SSc, than in patients with RP or healthy controls. Quantitative real‐time PCR with RNA from skin sections revealed that KDR mRNA levels were also increased in the skin of patients with SSc with elevated serum sKDR levels. A significantly lower prevalence of pulmonary fibrosis, higher percentage vital capacity, and a higher incidence of telangiectasia were seen in female patients with SSc with elevated serum sKDR levels than those with normal levels. Conclusions These results suggest that the skin can be one of the sources of elevated serum sKDR levels, and that serum sKDR levels are useful for diagnosis and may be a marker of microangiopathy in patients with SSc, especially females. The VEGF‐A/KDR signalling system may be involved in the pathogenesis of the disease.     

Elevation of IgG levels is a serological indicator for pulmonary fibrosis in systemic sclerosis with anti-topoisomerase I antibodies and those with anticentromere antibody

It is unclear whether any clinical and laboratory features are associated with pulmonary fibrosis (PF) in systemic sclerosis (SSc). We assessed these features using a database of 29 patients with SSc and anti-topoisomerase I antibodies and 68 patients with SSc and anticentromere antibody (ACA). Clinical features were not associated with the incidence of PF in patients with SSc and anti-topoisomerase I antibodies, although severe skin sclerosis was correlated with the presence of PF in patients with ACA. Serum IgG levels were often raised in patients with SSc and PF. Serum IgG levels in patients with PF were significantly higher than those in patients without PF, and were negatively correlated with percentage vital capacity and percentage diffusing capacity of the lung for carbon monoxide. In addition, serum IgG levels were correlated with serum interleukin-6. Thus, serum IgG levels are associated with PF in patients with SSc and anti-topoisomerase I antibodies and in patients with SSc and ACA.     

Serum levels of interleukin‐18‐binding protein isoform a: Clinical association with inflammation and pulmonary hypertension in systemic sclerosis

Systemic sclerosis (SSc) is a chronic autoimmune inflammatory disease characterized by extensive tissue fibrosis and various vascular complications. A wealth of evidence suggests the substantial contribution of pro‐inflammatory cytokines to the development of SSc, but the role of interleukin (IL)‐18 signaling in this disease still remains elusive. To address this issue, we herein determined serum levels of IL‐18‐binding protein isoform a (IL‐18BPa), a soluble decoy receptor for IL‐18, by enzyme‐linked immunosorbent assay in 57 SSc patients and 20 healthy controls and evaluated their clinical correlation. Serum IL‐18BPa levels were higher in SSc patients than in healthy controls, while comparable between diffuse cutaneous SSc and limited cutaneous SSc patients. Although serum IL‐18BPa levels were not associated with dermal and pulmonary fibrotic parameters in SSc patients, there was a significant positive correlation between serum IL‐18BPa levels and right ventricular systolic pressure estimated by echocardiography. Furthermore, in 24 SSc patients who underwent right heart catheterization, serum IL‐18BPa levels positively correlated with mean pulmonary arterial pressure. As for systemic inflammatory markers, significant positive correlations of circulating IL‐18BPa levels with erythrocyte sedimentation rate and C‐reactive protein were noted. These results suggest that the inhibition of IL‐18 signaling by IL‐18BPa may be involved in the development of pulmonary vascular involvement leading to pulmonary hypertension and modulate the systemic inflammation in SSc.     

Clinical significance of serum soluble T‐cell immunoglobulin and mucin domain 3 levels in systemic sclerosis: Association with disease severity

T‐cell immunoglobulin and mucin domain 3 (TIM‐3) has been thought to play a crucial role in the negative regulation of immune responses. Here, we examined the levels of serum soluble TIM‐3 (sTIM‐3) in patients with systemic sclerosis (SSc) and evaluated the results with respect to the clinical features of the disease. Patients with diffuse cutaneous SSc (dcSSc) had higher levels of sTIM‐3 than those with limited cutaneous SSc and healthy individuals. Serum sTIM‐3 levels were positively correlated with the severity of skin sclerosis in early phase dcSSc. Moreover, serum sTIM‐3 levels were increased more often in patients with renal crisis and cardiac involvement than in those with normal sTIM‐3 levels. These results suggest that serum sTIM‐3 levels may be increased in patients with early phase dcSSc and associated with cardiac involvement and renal crisis. Measurement of serum sTIM‐3 may be useful for risk stratification in the early stage of the disease.     

Decreased MMP-9 activity in the serum of patients with diffuse cutaneous systemic sclerosis

Matrix metalloproteinase-9 (MMP-9) and its inhibitor, tissue inhibitors of metalloproteinases-1 (TIMP-1) are involved in tissue inflammation and fibrotic processes. We previously reported an elevated serum TIMP-1 level in patients with systemic sclerosis (SSc). We measured serum TIMP-1 and active MMP-9 levels in 62 patients with SSc, 10 patients with rheumatoid arthritis (RA) and 15 normal controls using a modified enzyme-linked immunosorbent assay. The active MMP-9 level in the serum of the patients with RA or SSc was not significantly different from that of controls. Serum MMP-9 activity in patients with diffuse cutaneous SSc was significantly decreased compared with that of limited cutaneous SSc or normal controls. The MMP-9 activity and modified-Rodnan total skin thickness score in patients with SSc were negatively correlated. Serum MMP-9 activity and TIMP-1 level in patients with SSc were not correlated. Serum MMP-9 activity might be a useful indicator of disease activity, especially skin severity, in SSc patients.     

Serum levels of anti‐Fcγ receptor IIB/C antibodies are increased in patients with systemic sclerosis

Systemic sclerosis (SSc) is a systemic autoimmune disorder that results in fibrosis of the skin and multiple internal organs. Although the precise mechanism is unknown, it appears to result from the overproduction of extracellular matrix proteins and aberrant immune activations. Receptors for the Fc region of immunoglobulin (Ig)G (FcγR) are members of the Ig superfamily that modulate both activation and inhibition of immune responses. FcγRIIB is the sole inhibitory member, which has an intrinsic cytoplasmic immunoreceptor tyrosine‐based inhibitory motif. The present study was undertaken to investigate the circulating concentrations of anti‐FcγRIIB/C antibodies (Ab) in patients with SSc. Serum levels of anti‐FcγRIIB/C Ab were significantly increased in patients with SSc compared to those in controls and in patients with localized scleroderma. Serum levels of anti‐FcγRIIB/C Ab in patients with limited cutaneous SSc were similar to those in patients with diffuse cutaneous SSc. Among SSc patients, serum levels of anti‐FcγRIIB/C Ab were increased in those with nail‐fold bleeding and decreased in those with diffuse pigmentation and calcinosis. These findings support the notion that increased serum anti‐FcγRIIB/C Ab levels are involved in aberrant immune responses in SSc.     

Clinical significance of serum retinol binding protein‐4 levels in patients with systemic sclerosis

Background Retinol binding protein‐4 (RBP‐4) is a member of adipocytokines, which is potentially associated with fibrosis, vasodilation, and angiogenesis in addition to insulin resistance. Objective To investigate the clinical significance of serum RBP4 levels in patients with systemic sclerosis (SSc), which is a systemic autoimmune disease characterized by fibrosis and vasculopathy. Methods Serum RBP4 levels were determined by enzyme‐linked immunosorbent assay in 62 SSc patients and 19 healthy controls. Results Similar to patients with chronic kidney disease, serum RBP4 levels inversely correlated with estimated glomerular filtration rate in SSc patients with renal dysfunction. Therefore, analyses were carried out by excluding SSc patients with estimated glomerular filtration rate <60 mL/min/1.73 m². Serum RBP4 levels were significantly lower in diffuse cutaneous SSc (dcSSc) than in control subjects [median (25–75 percentile); 25.8 μg/mL (19.6–47.0) vs. 43.1 μg/mL (31.7–53.4), P < 0.05], while there was no significant difference between limited cutaneous SSc (lcSSc) [28.0 μg/mL (25.4–43.3)] and control subjects. In both of dcSSc and lcSSc, patients with Raynaud’s phenomenon had RBP4 levels significantly lower than those without. Furthermore, serum RBP4 levels inversely correlated with pulmonary function test results in dcSSc and with right ventricular systolic pressure in lcSSc. Conclusion Decreased RBP4 levels are associated with the prevalence of Raynaud’s phenomenon in dcSSc and lcSSc, with the severity of interstitial lung disease in dcSSc, and with the degree of pulmonary vascular involvement in lcSSc, suggesting the possible contribution of RBP4 to the pathological events in this disorder.     

Demonstration of interleukin-2, interleukin-4 and interleukin-6 in sera from patients with localized scleroderma

Localized scleroderma has been reported to be accompanied by immunological abnormalities related to B cells, but little is known about T-cell activation in this disease. In this study, serum levels of interleukin-2 (IL-2), interleukin-4 (IL-4) and interleukin-6 (IL-6), which are known to be released by activated T cells, were determined using a sensitive enzyme-linked immunosorbent assay in 48 patients with localized scleroderma and 20 with systemic sclerosis, and in 20 healthy control subjects. IL-2, IL-4 and IL-6 were detected in serum from patients with localized scleroderma but not in that from healthy controls. The presence of antihistone antibodies correlated significantly with elevated IL-4 and IL-6 levels. Decreased serum levels of IL-2, IL-4 and IL-6 paralleled improvement in cutaneous sclerosis. Frequent detection of these lymphokines in serum from patients with localized scleroderma reflects T-cell activation in this disorder.     

Serum levels of soluble IL-2 receptor, soluble ICAM-1, TNF-alpha, interleukin-4 and interleukin-6 in scleroderma

Background A variety of immunological markers have been reported to be elevated in patients with systemic scleroderma (SSc). Objective The aim of this study was to determine which of the following parameters: soluble IL-2 receptor (sIL-2r). soluble ICAM-1 (sICAM-1), tumour necrosis factor (TNF-alpha), interleukin-6 (IL-6) and interleukin-4 (IL-4) reflect the clinical stage of the disease and how they correlate with each other. Methods In 31 scleroderma patients the serum levels of these markers were measured in the same blood sample using ELISA test kits. The results were correlated with clinical findings such as extent of skin disease, inflammatory disease activity and involvement of internal organs. Results SIL-2r, slCAM-1 and TNF-alpha showed significant differences in subgroups of SSc patients in contrast to IL-4and IL-6, The five parameters did not correlate with each other. Conclusion sIL-2r, sICAM-1 and TNF-alpha showed differences in subgroups of scleroderma and therefore they may be useful in further studies as markers of disease activity.     

Elevated MMP-7 levels in patients with systemic sclerosis: correlation with pulmonary involvement

Background: Fibrosis is characterized by an excessive accumulation of connective tissue because of an imbalance between synthesis and degradation of extracellular matrix proteins. Systemic sclerosis (SSc) is a prototypic chronic inflammatory disease leading to a severe fibrosis of the skin and many internal organs. Questions Addressed: We investigated whether serum MMP‐7 levels reflect the activity of the fibrotic reaction in systemic sclerosis. Experimental Design: Serum samples were obtained from 123 patients with systemic sclerosis. MMP‐serum levels of all patients with SSc were compared with age‐matched healthy controls. Results: Significantly increased median serum MMP‐7 levels were found in patients with SSc when compared with controls. The median MMP‐7 serum level of patients with lung fibrosis (LF) was significantly higher compared with those without LF. Accordingly, patients with dyspnea and DLCO (diffusion capacity of the lung for carbon monoxide) levels below 60% showed significantly higher median MMP‐7 levels. Conclusions: Elevated MMP‐7 levels are associated with an advanced stage of SSc and LF. These data suggest that in SSc MMP‐7 is involved in the process of fibrotic tissue remodelling.     

Serum levels of ADAM12‐S: possible association with the initiation and progression of dermal fibrosis and interstitial lung disease in patients with systemic sclerosis

Background A disintegrin and metalloprotease (ADAM) 12 is one of the metalloproteinase‐type ADAMs and possesses extracellular metalloprotease and cell‐binding functions. ADAM12 is expressed in two alternative forms, such as a membrane‐anchored form (ADAM12‐L) and a short secreted form (ADAM12‐S). Objective To investigate the clinical significance of serum ADAM12‐S levels in systemic sclerosis (SSc). Methods Serum ADAM12‐S levels were determined by a specific enzyme‐linked immunosorbent assay in 61 SSc patients and 18 healthy controls. Results Serum ADAM12‐S levels were significantly increased in diffuse cutaneous SSc (dcSSc) patients than in healthy controls (0.417 ± 0.389 vs. 0.226 ± 0.065 ng/mL; P < 0.05), while being comparable between limited cutaneous SSc (0.282 ± 0.258 ng/mL) and healthy controls. Serum ADAM12‐S levels significantly elevated in dcSSc patients with disease duration of ≤6 years (0.537 ± 0.449 ng/mL, P < 0.05), but not in dcSSc with disease duration of >6 years (0.225 ± 0.049 ng/mL), compared to healthy controls. Furthermore, in dcSSc patients with disease duration of ≤6 years, serum ADAM12‐S levels correlated positively with modified Rodnan total skin thickness score, ground glass score, and serum C‐reactive protein values, while showed inverse correlation with fibrosis score. Conclusion Elevated serum ADAM12‐S levels are associated with elevated serum inflammatory marker, severity of skin fibrosis, and activity of interstitial lung disease in dcSSc, suggesting the possible contribution of ADAM12‐S to the pathological events in this disorder.     

A clue for telangiectasis in systemic sclerosis: elevated serum soluble endoglin levels in patients with the limited cutaneous form of the disease

BACKGROUND: The transforming growth factor-beta (TGF-beta) 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-beta 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.