Clinical significance of surfactant protein D as a serum marker for evaluating pulmonary fibrosis in patients with systemic sclerosis.

OBJECTIVE: To determine the clinical significance of surfactant protein D (SP-D), a useful marker for evaluating various lung diseases, in patients with systemic sclerosis (SSc) and to clarify any clinical significance between SP-D and KL-6, which is known to be correlated with pulmonary fibrosis (PF) in SSc patients. METHODS: We used a specific enzyme-linked immunosorbent assay to measure serum SP-D levels in 83 patients with SSc and 31 healthy control subjects. RESULTS: The serum levels of SP-D were significantly higher in patients with SSc than in healthy controls (mean +/- SD 81.9+/-59.2 versus 34.8+/-13.7 ng/ml). Serum SP-D levels in patients with diffuse cutaneous SSc were significantly higher than those in patients with limited cutaneous SSc (98.8+/-72.1 versus 66.8+/-40.0 ng/ml). Serum SP-D levels in patients with PF were significantly elevated compared with those in patients without PF (99.7+/-64.1 versus 65.3+/-49.4 ng/ml). Moreover, the incidences of decreased percentage diffusing capacity for carbon monoxide and decreased percentage vital capacity were also significantly greater in patients with elevated SP-D levels than in those with normal levels (67% versus 43% and 36% versus 17%, respectively). There was a significant positive correlation between serum levels of SP-D and KL-6. Serum SP-D and KL-6 levels showed almost the same sensitivities and specificities in the diagnosis of PF (68% versus 73% and 70% versus 74%, respectively). These two markers also predicted PF to almost the same degree (31% versus 33%, respectively). CONCLUSION: These results suggest that SP-D, as well as KL-6, may be a useful serum marker for evaluating PF in patients with SSc.     

Clinical significance of KL-6, a marker of interstitial pneumonia,in cases of HCV-associated chronic liver disease

OBJECTIVE: Various antiviral therapies, including interferon therapy, are being conducted to treat chronic hepatitis C and suppress the onset of hepatocellular carcinoma. However, interstitial pneumonia is beginning to be recognized as one of the adverse reactions of this therapy, and is one of the complications associated with chronic hepatitis. Therefore, we measured the level of KL-6, an interstitial pneumonia marker, in patients with HCV-associated chronic disease, and then determined the possibility of utilizing serum KL-6 as a predictive factor for interstitial pneumonia and the clinical significance of KL-6 in HCV-associated chronic disease. SUBJECTS AND METHODS: The subjects were 308 patients who were diagnosed with chronic liver disease through biochemical blood tests and abdominal diagnostic imaging. All patients tested positive for either the HCV antibody or HCV-RNA, and those who were suspected of having autoimmune hepatitis were excluded. One hundred eighty-five patients had chronic hepatitis (average age: 56 +/- 14 years), while 123 patients had liver cirrhosis (average age: 64 +/- 9 years). The purpose of the present study was explained to every subject, and informed consent was obtained. RESULTS: The mean KL-6 level for chronic hepatitis patients without interstitial pneumonia was 283.5 +/- 131.4 U/ml, while that for cirrhotic patients without interstitial pneumonia was significantly higher, at 377.6 +/- 212.1 U/ml (p<0.0001). In addition, with a cut-off value of 500 U/ml, the ratio of high KL-6 for the chronic hepatitis patients was 5.41% (10/185), while that for the cirrhotic patients was significantly higher, at 20.33% (25/123) (p<0.0001). Furthermore, the mean KL-6 level for patients with a serum hyaluronic acid level of less than 100 ng/ml was 258.4 +/- 124.6 U/ml, while that for patients with a serum hyaluronic acid level of 100 ng/ml or above was significantly higher, at 381.0 +/- 197.3 U/ml (p<0.0001). CONCLUSION: Although KL-6 is a marker of interstitial pneumonia, the results of the present study suggest that, in HCV-associated chronic disease, this marker reflects hepatic fibrosis better than pulmonary fibrosis.     

Comparative study of serum surfactant protein-D and KL-6 concentrations in patients with systemic sclerosis as markers for monitoring the activity of pulmonary fibrosis

OBJECTIVE: To clarify the clinical significance of surfactant protein-D (SP-D) and KL-6 in the diagnosis and monitoring of pulmonary fibrosis (PF) in patients with systemic sclerosis (SSc), and to evaluate the differences between SP-D and KL-6. METHODS: Serum SP-D and KL-6 concentrations were determined by ELISA in 42 SSc patients. In a retrospective longitudinal study, 83 serum samples from 6 SSc patients were analyzed during a followup period of 0.6-6.3 years. RESULTS: SP-D and KL-6 concentrations at the first visit were higher in patients with SSc, especially those with PF, compared with healthy controls. Increased concentrations of SP-D were associated with decreased DLCO and decreased vital capacity in SSc patients more strongly than those of KL-6. The sensitivity and specificity for PF were 91% and 88% for SP-D and 39% and 100% for KL-6, respectively. In the longitudinal study, both SP-D and KL-6 concentrations were associated with activity of PF in patients with SSc. SP-D concentrations changed more rapidly than KL-6 concentrations, in parallel with the PF activity. CONCLUSION: SP-D was a more sensitive marker for PF than KL-6. By contrast, KL-6 showed higher specificity than SP-D. Combined use of these 2 serum markers would be more helpful to diagnose and monitor the PF activity in patients with SSc than single use of each marker.     

Clinical significance of serum levels of matrix metalloproteinase-13 in patients with systemic sclerosis

OBJECTIVES: To investigate the clinical significance of serum matrix metalloproteinase-13 (MMP-13) levels in patients with systemic sclerosis (SSc). METHODS: Serum MMP-13 levels were determined by using a peptide substrate cleavage assay in 20 patients with diffuse cutaneous SSc (dcSSc), 20 with limited cutaneous SSc (lcSSc) and 10 normal controls. RESULTS: The serum MMP-13 levels in patients with dcSSc or lcSSc were significantly lower than those in normal controls (53.4 +/- 14.1 vs 73.2 +/- 11.5 ng/ml, P < 0.0005; 59.4 +/- 14.8 vs 73.2 +/- 11.5 ng/ml, P < 0.005, respectively), but there was no significant difference in the serum MMP-13 levels between patients with dcSSc and those with lcSSc. Disease duration prior to the diagnosis was significantly shorter in SSc patients with decreased serum MMP-13 levels than in those with normal levels (3.0 +/- 2.2 vs 8.6 +/- 7.6 yr, P < 0.0005). In addition, serum MMP-13 levels were moderately correlated with the duration of the disease (r = 0.451, P < 0.05). Though there was no significant difference in the frequencies of pulmonary fibrosis or reduced %DLco (diffusing capacity of lung for carbon monoxide), the frequency of reduced %VC (vital capacity) was significantly greater in patients with decreased serum MMP-13 levels than in those with normal levels (73 vs 24%, P < 0.05). CONCLUSIONS: Matrix metalloproteinase-13 may be involved in the fibrotic process of SSc, especially in the initiation of fibrosis. The serum MMP-13 levels may serve as a useful marker for the severity of pulmonary fibrosis in patients with SSc.     

Serum pulmonary and activation-regulated chemokine/CCL18 levels in patients with systemic sclerosis: a sensitive indicator of active pulmonary fibrosis

OBJECTIVE: To clarify the clinical significance of serum levels of pulmonary and activation-regulated chemokine (PARC) in the diagnosis and monitoring of pulmonary fibrosis (PF) in patients with systemic sclerosis (SSc) and to compare PARC levels with KL-6 antigen or surfactant protein D (SP-D) levels. METHODS: Serum PARC levels were determined by enzyme-linked immunosorbent assay in 123 SSc patients. In a retrospective longitudinal study, correlation of serum PARC levels with the activity of PF was assessed in 21 SSc patients with active PF. RESULTS: PARC levels at the first visit were higher in patients with SSc than in patients with systemic lupus erythematosus (SLE) or healthy controls. Increased serum PARC levels were associated with involvement of PF, decreased diffusing capacity for carbon monoxide, and decreased vital capacity in SSc patients. In the longitudinal study, serum PARC levels were significantly decreased in SSc patients with inactive PF compared with those with active PF. CONCLUSION: Elevated serum PARC levels correlated with PF and more sensitively reflected the PF activity than did serum KL-6 or SP-D levels in SSc. Serum PARC levels may be a useful new serum marker for active PF in SSc.     

Longitudinal analysis of serum KL-6 levels in patients with systemic sclerosis: association with the activity of pulmonary fibrosis

OBJECTIVE: To determine whether changes in serum KL-6 levels reflect the activity of pulmonary fibrosis (PF) in patients with systemic sclerosis (SSc). METHODS: KL-6 levels were determined by ELISA in 39 SSc patients. In a retrospective longitudinal study, 250 serum samples were analyzed during a follow-up period of 0.3-6.1 years. RESULTS: KL-6 levels at the first visit were higher in patients with SSc, especially with PF, compared with healthy controls. In the longitudinal study, KL-6 levels in 4 patients with anti-topo I Abs increased rapidly, parallel to the progression of PF. Four patients with inactive PF exhibited elevated, but stable levels of KL-6 during the follow-up. The 31 patients with almost normal KL-6 levels during the follow-up exhibited no deterioration or new onset of PF. CONCLUSION: Rapidly increased serum KL-6 levels during disease course were associated with new onset or deterioration of PF.     

Prognostic value of serial serum KL-6 measurements in patients with idiopathic pulmonary fibrosis

Background

The prognostic significance of serial measurements of serum KL-6 levels in patients with idiopathic pulmonary fibrosis (IPF) is unclear; hence, it was assessed in this study.

Clinical significance of surfactant protein D as a serum marker for evaluating pulmonary fibrosis in patients with systemic sclerosis

Objective

To determine the clinical significance of surfactant protein D (SP‐D), a useful marker for evaluating various lung diseases, in patients with systemic sclerosis (SSc) and to clarify any clinical significance between SP‐D and KL‐6, which is known to be correlated with pulmonary fibrosis (PF) in SSc patients.

Methods

We used a specific enzyme‐linked immunosorbent assay to measure serum SP‐D levels in 83 patients with SSc and 31 healthy control subjects.

Results

The serum levels of SP‐D were significantly higher in patients with SSc than in healthy controls (mean ± SD 81.9 ± 59.2 versus 34.8 ± 13.7 ng/ml). Serum SP‐D levels in patients with diffuse cutaneous SSc were significantly higher than those in patients with limited cutaneous SSc (98.8 ± 72.1 versus 66.8 ± 40.0 ng/ml). Serum SP‐D levels in patients with PF were significantly elevated compared with those in patients without PF (99.7 ± 64.1 versus 65.3 ± 49.4 ng/ml). Moreover, the incidences of decreased percentage diffusing capacity for carbon monoxide and decreased percentage vital capacity were also significantly greater in patients with elevated SP‐D levels than in those with normal levels (67% versus 43% and 36% versus 17%, respectively). There was a significant positive correlation between serum levels of SP‐D and KL‐6. Serum SP‐D and KL‐6 levels showed almost the same sensitivities and specificities in the diagnosis of PF (68% versus 73% and 70% versus 74%, respectively). These two markers also predicted PF to almost the same degree (31% versus 33%, respectively).

Conclusion

These results suggest that SP‐D, as well as KL‐6, may be a useful serum marker for evaluating PF in patients with SSc.

     

Serum level of KL-6 as a marker of interstitial lung disease in patients with juvenile systemic sclerosis

OBJECTIVE: Serum KL-6 has been found to be elevated in diseases characterized by diffuse interstitial lung involvement. The purpose of this study was to evaluate serum KL-6 as a marker of interstitial lung disease (ILD) in patients with juvenile systemic sclerosis (JSS). METHODS: Serum concentrations of KL-6 were measured with an immunoassay in 39 serum samples from 12 children with diffuse cutaneous form of JSS (6 patients with and 6 patients without ILD) and from 20 healthy controls comparable for age. In patients sampled serially, the relationship of KL-6 concentrations with the severity of ILD and its response to treatment were evaluated. RESULTS: Serum concentrations of KL-6 were significantly higher in patients with ILD (1687 +/- 979 IU/ml) than in patients without (345 +/- 95 IU/ml, p < 0.01) and healthy controls (311 +/- 114 IU/ml, p < 0.001). Serum KL-6 concentrations of patients without ILD were not statistically different from those of healthy controls. We found a significant correlation of serum KL-6 concentrations with vital capacity and with diffusing capacity for carbon monoxide (DLCO). Analysis of individual patients showed that serum concentrations of KL-6 were correlated with ILD severity and its response to treatment. CONCLUSION: Measurement of serum KL-6 concentration is a useful noninvasive marker of pulmonary fibrosis in children with JSS. Its advantages over conventional methods of ILD assessment, such as pulmonary function test and high-resolution computerized tomography, are that it is easy to quantify and to measure repeatedly and it does not need children's cooperation.     

The usefulness of serum KL-6 levels for the diagnosis of disease activity in idiopathic interstitial pneumonia]

Serum KL-6 levels were measured in 29 patients with idiopathic interstitial pneumonia (IIP) as a means of evaluating disease activity. Levels of serum KL-6 were significantly higher in patients with active IIP (n = 11) than in those with inactive IIP (n = 18). The levels of serum KL-6 were 2,546 +/- 1,703 U/ml in patients with active IIP and 795 +/- 385 U/ml in patients with inactive IIP, respectively. The levels of serum LDH, CEA, P-III-P, and 7 S collagen in patients with active IIP did not differ significantly from those in patients with inactive IIP. For the diagnosis of active IIP, the sensitivity of serum KL-6 (cut off value of 1,500 U/ml) was 81.8% and the specificity, 94.4%. These results were almost identical to findings obtained with chest Ga-67 scintigraphy. Furthermore, they suggested that serum KL-6 levels may be a useful marker for the diagnosis of disease activity in IIP, as well as a useful indicator for the administration of steroid therapy to patients with IIP.     

Comprehensive investigation of novel serum markers of pulmonary fibrosis associated with systemic sclerosis and dermato/polymyositis

OBJECTIVE: To investigate the association between serum levels and clinical signs of lung fibrosis in patients with systemic sclerosis and inflammatory myopathies. METHODS: ELISA tests for a mucin-like glycoprotein KL-6, von Willebrandt factor (vWF), soluble E-selectin (sES) and surfactant protein D (SP-D) were performed in sera of 104 patients with systemic sclerosis, 31 patients with poly/dermatomyositis) and 24 patients with Raynaud's phenomenon as controls. The clinical and laboratory data were evaluated by a simple standard protocol including chest x-ray, lung function tests, echocardiography and, in selected cases, high resolution computer tomography (HRCT). Clinically significant pulmonary fibrosis (PF) defined as a simultaneous presence of radiological sign of pulmonary fibrosis and restrictive impairment. Severe PF was established if HRCT scans showed diffuse interstitial lung disease with low diffusing capacity. End stage PF was determined as severe PF with very low diffusing capacity. RESULTS: Patients with pulmonary fibrosis on chest x-ray showed significantly elevated serum levels of KL-6, SP-D and vWF. Inverse correlation was found between serum levels of KL-6/SP-D and lung function parameters, such as DLCO% and FVC. With regard to HRCT findings, patients with elevated serum level of KL-6 showed significantly more frequently ground glass opacity, diffuse and honeycombing fibrosis than patients with normal level of KL-6. The sensitivity of KL-6 for PF in SSc is increased with the severity of PF (PF on chest x-ray < severe PF < end stage of PF). Lung fibrosis occurred more frequently in patients with simultaneously elevated KL-6 and sES compared to cases with a single positivity of either KL-6 or sES. CONCLUSION: KL-6, SP-D, vWF and ES are good surrogate factors of pulmonary fibrosis but can not replace conventional diagnostic procedures. However, these markers are suitable for the assessment of progression and severity of pulmonary fibrosis in systemic autoimmune disorders once the diagnosis is established.     

Increased levels of KL-6 and subsequent mortality in patients with interstitial lung diseases

OBJECTIVES: KL-6 is a specific marker in patients with interstitial lung diseases (ILDs); however, the relationship between elevated levels of KL-6 and subsequent mortality is not well defined. To determine if elevated serum levels of KL-6 are associated with increased mortality, and to identify the most suitable cut-off level of KL-6 by which to distinguish between good prognosis and poor prognosis, we evaluated the prognostic significance of serum KL-6 levels in patients with stable-state ILDs. METHODS: Two hundred and nineteen patients diagnosed with ILDs (152 with idiopathic interstitial pneumonia and 67 with collagen disease-associated pulmonary fibrosis) at Tsukuba University Hospital from April 1999 to October 2005 were entered in this study. Serum KL-6 levels in patients with ILDs were measured with a commercially available enzyme immunoassay kit, and these patients were then followed up. RESULTS: During the follow-up period, 58 of the 219 patients died of respiratory failure. Patients who died during this period had higher levels of KL-6 than did those who did not (P = 0.0004). The receiver operating characteristic curve analysis showed 1000 U mL(-1) as the most suitable cut-off level by which to distinguish between the two groups of patients. The 95% specificity serum KL-6 level with poor outcome was 2750 U mL(-1). In univariate and multivariate analysis, elevated serum KL-6 (>1000 U mL(-1)) in the stable state indicated poor prognosis (P = 0.0005, log-rank test; P = 0.0001, Cox proportional hazard model). CONCLUSIONS: Elevated KL-6 level may provide simple, yet valuable information by which to identify patients with ILDs who are at increased risk for subsequent mortality.     

Elevation of serum KL-6 levels in patients with hematological malignancies associated with cytomegalovirus or Pneumocystis carinii pneumonia

The level of serum KL-6 antigen has been reported to be a sensitive indicator of various interstitial pneumonitis, but in patients with hematological malignancies who were accompanied by infective interstitial pneumonitis like Pneumocystis carinii or cytomegalovirus (CMV) pneumonia, it is still unknown whether serum KL-6 level is useful as a good marker for the diagnosis or disease activity. In this study, the serum levels of KL-6 and soluble intercellular adhesion molecule 1 (sICAM-1) were evaluated in five patients with malignant lymphoma or adult T-cell leukemia. Serum KL-6 and sICAM-1 levels at the time of diagnosis of P. carinii or CMV pneumonia were 1220+/-323 U/ml (mean+/-SD) and 1246+/-485 ng/ml, respectively. These levels were apparently high, when compared with standard value of serum KL-6 (<520 U/ml) and that of sICAM-1 (115-306 ng/ml). In patients without P. carinii or CMV pneumonia, who had hematological malignancies or AIDS, serum level of KL-6 was not high (299+/-122 U/ml), but sICAM-1 was high (651+/-495 ng/ml) because of the elevation of sICAM-1 in four of five cases. These findings suggest that, in patients with hematological malignancies, serum level of KL-6 antigen rather than sICAM-1 may be useful in the evaluation of CMV or P. carinii pneumonia.     

Elevated vascular endothelial growth factor in systemic sclerosis

OBJECTIVE: To determine the serum levels of vascular endothelial growth factor (VEGF) in patients with systemic sclerosis (SSc) and to search for relationships between its serum levels and the clinical manifestations. METHODS: Serum levels of VEGF in patients with SSc and healthy controls were determined by ELISA. At the time of blood sampling, individual organ involvement was assessed, and a video microscope and PC based image processing were used to visualize nailfold capillaries and to quantify capillary density. RESULTS: Serum levels of VEGF in 48 patients with SSc were significantly higher than in 30 controls (432 +/- 356 vs 91 +/- 64 pg/ml; p < 0.001). Patients with diffuse cutaneous SSc (n = 21) had higher levels of serum VEGF than those with limited cutaneous SSc (n = 27) (432 +/- 356 vs 135 +/- 127 pg/ml; p < 0.001). Serum VEGF levels correlated well with the extent of skin sclerosis, as determined by modified Rodnan skin score (r = 0.656, p < 0.001) and serum TGF-beta levels (r = 0.530, p < 0.001). In particular, serum VEGF levels were inversely correlated with the capillary density of nailfold (r = -0.649, p < 0.001). However, no significant differences were found in the serum levels of VEGF between patients with systemic organ involvement and those without. CONCLUSION: The extent of skin sclerosis may contribute to the elevation of serum VEGF and high VEGF levels may serve as a surrogate indicator of capillary damage in SSc.     

Clinical significance of serum levels of secretory leukocyte protease inhibitor in patients with systemic sclerosis

Abstract

We aimed to investigate the clinical significance of serum levels of secretory leukocyte protease inhibitor (SLPI), which is widely expressed in lung tissues and serves as a useful marker reflecting the activity of various lung diseases, in patients with systemic sclerosis (SSc). Serum SLPI levels were measured by a specific enzyme-linked immunosorbent assay (ELISA) in 58 SSc patients and 16 healthy controls. Serum SLPI levels in diffuse cutaneous SSc and in limited cutaneous SSc with interstitial lung disease (ILD) were significantly higher than those in healthy controls (43.1 ± 18.4 vs. 30.9 ± 3.76 ng/ml, p < 0.05 and 39.8 ± 10.3 vs. 30.9 ± 3.76 ng/ml, p < 0.01, respectively). The incidences of decreased percent diffusing capacity for carbon monoxide (%DLco) and decreased percent vital capacity (%VC) were significantly greater in SSc patients with elevated SLPI levels than in those with normal levels (73 vs. 31%, p < 0.01 and 24 vs. 4%, p < 0.05, respectively). Furthermore, serum SLPI levels were inversely correlated with %DLco (r = ?0.40, p < 0.01), while they were positively correlated with surfactant protein D (r = 0.28, p < 0.05). Longitudinal study revealed the association of serum SLPI levels with the disease activity of SSc-ILD. SLPI serves as a useful serum marker for evaluating SSc-ILD.     

Increased serum fractalkine in systemic sclerosis. Down-regulation by prostaglandin E1

OBJECTIVES:To evaluate serum levels of fractalkine (FKN), a mediator of leukocyte transmigration, C-reactive protein (CRP) and expression of integrins CD11a and CD49d on peripheral blood lymphocytes in systemic sclerosis (SSc) and to investigate whether they are modulated by intravenous prostaglandin E1 (PGE1). METHODS:Serum levels of fractalkine and C-reactive protein and expression of CD11a and CD49d on peripheral blood lymphocytes were assessed in 50 SSc patients and in 18 healthy controls. In 25 SSc patients studied parameters were evaluated also after 3 consecutive daily PGE1 infusions (20 microg-40 microg-60 microg) and after 4 weeks. RESULTS:In SSc fractalkine basal level was significantly higher than in controls (9.04+/-1.79 ng/ml vs. 1.17+/-0.1 ng/ml; p<0.0001) and decreased significantly after PGE1 (5.16+/-1.27 ng/ml, p<0.05). After four weeks fractalkine level was still significantly lower than baseline 7.70+/-2.19 ng/ml (p<0.05). Basal percentage of CD11a (+) nor CD49d (+) lymphocytes in SSc (82.38+/-1.60%, 70.74+/-1.68%, respectively) did not differ from controls (85.73+/-2.04%, 75.62+/-2.48%; respectively, p>0.05). PGE1 treatment resulted in decrease of both CD11a (+) (67.72+/-3.34%, p<0.0001) and CD49d (+) lymphocytes (65.32+/-1.62%, p<0.0001). After 4 weeks the percentage of CD11a (+) and CD49d (+) lymphocytes remained significantly lower than at baseline (77.80+/-2.47% and 65.32+/-1.62%, respectively, both p<0.001). In SSc CRP basal level was significantly higher than in controls (4.70+/-2.01 mg/dl vs. 1.40+/-1.79 mg/dl, p<0.005) and reduced significantly after PGE1 (3.39+/-2.06 mg/dl, p<0.05). After 4 weeks, CRP level (4.38+/-2.19 ng/ml) was significantly lower than baseline (p<0.05).CONCLUSION:Fractalkine may play an important role in the pathogenesis of vascular dysfunction in systemic sclerosis. Prostaglandin E1 down-regulates serum fractalkine level, as well as CD11a and CD49d expression on peripheral blood lymphocytes, which suggests additional mechanisms in which this vasodilatatory agent exerts its efficacy in systemic sclerosis.     

CXCL10 (alpha) and CCL2 (beta) chemokines in systemic sclerosis--a longitudinal study

OBJECTIVES: To measure serum levels of CXCL10 and CCL2 chemokines in patients with SSc, and relate the findings to clinical phenotype and disease progression. METHODS: Serum CXCL10 and CCL2 were assayed in 72 consecutive newly diagnosed SSc patients and in 72 sex- and age-matched controls. In 37 SSc and 37 controls, serum CXCL10 and CCL2 were re-evaluated 5 yrs later. RESULTS: SSc at onset showed significantly higher CXCL10 serum levels than controls (216 +/- 126 vs 92 +/- 53 pg/ml; P < 0.0001), as well as CCL2 (388 +/- 172 vs 318 +/- 120 pg/ml; P = 0.01). CXCL10 was significantly increased in SSc with interstitial lung involvement or with kidney involvement (P = 0.01 and P = 0.02, respectively). A significant decrease of CXCL10 was observed from the baseline after 5 yrs in SSc (137 +/- 112 vs 270 +/- 122 pg/ml, respectively; P < 0.0001), while no significant change was observed for CCL2 (418 +/- 176 vs 405 +/- 164 pg/ml; P = NS); the CCL2/CXCL10 ratio significantly increased at the fifth year (1.7 +/- 0.8 vs 3.5 +/- 2.5; P < 0.0001). No significant variations were observed in controls from the basal to the 5-yr evaluation with regards to CXCL10, CCL2 or CCL2/CXCL10 ratio. CONCLUSIONS: Our study demonstrates high serum levels of CXCL10 (Th1) and CCL2 (Th2) chemokines in newly diagnosed SSc. High values of CXCL10 are associated with a more severe clinical phenotype (lung and kidney involvement). CXCL10 declined during the follow-up, while CCL2 remained unmodified, suggesting that the disease progresses from the early Th1 inflammatory condition to the advanced Th2-like stage.     

血清KL-6水平在胰腺癌诊断与鉴别诊断中的价值

目的 检测胰腺癌患者血清KL-6水平,探讨其临床诊断价值.方法 收集随访资料完整的53例胰腺癌(PC)、68例慢性胰腺炎(CP)、51例高危人群(high risk person,HR)的血清样本,以50例健康体检者作为对照.用ELISA方法检测血清CA50、MUCA、KL-6水平,放免法测定血清CA19-9水平.分析它们诊断胰腺癌的敏感性、特异性及与临床病理参数、患者预后的关系.结果 PC组、CP组、HR组及对照组的血清KL-6水平分别为(753±548)、(135 ±93)、(105±55)及(99±50)U/ml,PC组显著高于其他3组(P<0.01).以>232 U/ml为界,KL-6诊断胰腺癌的敏感性为96%,特异性为94%;以>244 U/ml为界,鉴别诊断PC与CP的敏感性为97%,特异性为91%.KL-6诊断胰腺癌的临床价值高于CA19-9、CA50及MUC4.胰腺癌患者血清KL-6水平与肿瘤的临床病理参数均无相关性.血清KL-6≤300 U/ml患者的平均生存期为(9.3±1.2)个月,较KL-6>300 U/ml患者平均生存期(4.6±0.7)个月显著延长(P=0.006).结论 KL-6可作为诊断胰腺癌的血清学指标,且对胰腺癌和慢性胰腺炎的鉴别诊断有一定意义.     

血清KL-6检测在COPD合并肺间质纤维化诊断中的意义

目的研究慢性阻塞性肺疾病合并肺间质纤维化患者血清KL-6水平的变化。方法选取COPD合并PIF患者22例,单纯COPD患者23例,另选取20例健康志愿者为对照组。所有入选者均行胸部CT或HRCT及肺功能检查,ELISA检测血清KL-6水平,并分析其与肺功能相关指标的相关性。结果 COPD合并PIF组患者血清KL-6水平(1048±452 U/ml)较单纯COPD组患者(429±226 U/ml)及健康对照组(384±108 U/ml)显著升高(P0.05),而单纯COPD组患者血清KL-6水平与健康对照组相比无显著性差异(P0.05);血清KL-6水平与DL CO呈显著负相关(P0.05),但与用力肺活量(FVC)(P0.05)、1 s用力呼气容积(FEV1)(P0.05)及FEV1/FVC无明显相关性(P0.05)。结论 COPD合并PIF患者血清KL-6水平明显增高,血清KL-6也许可作为诊断COPD合并PIF的血清学指标。     

Serum levels of heat shock protein 70, a biomarker of cellular stress, are elevated in patients with systemic sclerosis: association with fibrosis and vascular damage

OBJECTIVE: To determine the clinical significance of heat shock protein (Hsp) 70, a sensitive biomarker for monitoring cellular stress, in systemic sclerosis (SSc), we investigated the prevalence and clinical correlation of serum Hsp70 levels in SSc patients. METHODS: Serum Hsp70 levels were examined in 48 patients with SSc by enzyme-linked immunosorbent assay. RESULT: Serum Hsp70 levels were significantly elevated in SSc patients compared to normal controls (n=30), and were similar between patients with diffuse cutaneous SSc (n=26) and those with limited cutaneous SSc (n=22). Serum Hsp70 levels were elevated in 27% of total SSc patients with 30% of diffuse cutaneous SSc patients and 23% of limited cutaneous SSc patients. Hsp70 levels were significantly increased in SSc patients with pulmonary fibrosis or contracture of phalanges compared with those without pulmonary fibrosis or contracture of phalanges. Serum Hsp70 levels correlated positively with modified Rodnan total skin thickness score, renal vascular resistance, serum levels of monocyte chemotactic protein-1, C-reacting protein, and serum levels of 8-isoprostane. CONCLUSION: Serum Hsp70 levels were increased in SSc patients and were associated with pulmonary fibrosis, skin sclerosis, renal vascular damage, oxidative stress, and inflammation. These results suggest that Hsp70 is a useful serological marker for evaluating cellular stresses and the disease severity in SSc.