Limits...
Serum amyloid A is a marker for pulmonary involvement in systemic sclerosis.

Lakota K, Carns M, Podlusky S, Mrak-Poljsak K, Hinchcliff M, Lee J, Tomsic M, Sodin-Semrl S, Varga J - PLoS ONE (2015)

Bottom Line: Elevated levels of SAA were found in 25% of SSc patients, with the highest levels in those with early-stage disease and diffuse cutaneous involvement.Significant negative correlations of SAA were found with forced vital capacity and diffusion capacity for carbon monoxide.Patients with elevated SAA had greater dyspnea and more frequent interstitial lung disease, and had worse scores on patient-reported outcome measures.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia; Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, United States of America.

ABSTRACT
Inflammation in systemic sclerosis (SSc) is a prominent, but incompletely characterized feature in early stages of the disease. The goal of these studies was to determine the circulating levels, clinical correlates and biological effects of the acute phase protein serum amyloid A (SAA), a marker of inflammation, in patients with SSc. Circulating levels of SAA were determined by multiplex assays in serum from 129 SSc patients and 98 healthy controls. Correlations between SAA levels and clinical and laboratory features of disease were analyzed. The effects of SAA on human pulmonary fibroblasts were studied ex vivo. Elevated levels of SAA were found in 25% of SSc patients, with the highest levels in those with early-stage disease and diffuse cutaneous involvement. Significant negative correlations of SAA were found with forced vital capacity and diffusion capacity for carbon monoxide. Patients with elevated SAA had greater dyspnea and more frequent interstitial lung disease, and had worse scores on patient-reported outcome measures. Incubation with recombinant SAA induced dose-dependent stimulation of IL-6 and IL-8 in normal lung fibroblasts in culture. Serum levels of the inflammatory marker SAA are elevated in patients with early diffuse cutaneous SSc, and correlate with pulmonary involvement. In lung fibroblasts, SAA acts as a direct stimulus for increased cytokine production. These findings suggest that systemic inflammation in SSc may be linked to lung involvement and SAA could serve as a potential biomarker for this complication.

Show MeSH

Related in: MedlinePlus

SAA levels are correlated with pulmonary function.Correlation between serum levels of SAA and pulmonary function tests (A, B);pulmonary artery pressure (C); serum BNP levels (D). The horizontal linerepresents the SAA cut-off (19.5μg/ml) and vertical line cut-off forpulmonary arterial hypertension (right heart catheterization mPAO≥25mmHg). Spearman correlation coefficient (r), p value, and number of patients(n) are shown.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4321755&req=5

pone.0110820.g002: SAA levels are correlated with pulmonary function.Correlation between serum levels of SAA and pulmonary function tests (A, B);pulmonary artery pressure (C); serum BNP levels (D). The horizontal linerepresents the SAA cut-off (19.5μg/ml) and vertical line cut-off forpulmonary arterial hypertension (right heart catheterization mPAO≥25mmHg). Spearman correlation coefficient (r), p value, and number of patients(n) are shown.

Mentions: Patients with elevated SAA had significantly impaired pulmonary function (Table 2). In particular, SAAlevels were inversely correlated with FVC (r = −0.253, p = 0.01) and DLCO (r =−0.320, p = 0.002) (Fig. 2A and 2B). Moreover,different radiologic patterns of lung involvement were associated with significantdifferences (Kruskal-Wallis χ2df = 3 = 9.23, p = 0.03)in SAA levels (S2Table). Of note, patients with elevated SAA were 6.3 times more likely tohave reduced DLCO (< 70% of predicted; 95% CI 1.36–28.91), and 3.7times more likely to show a honeycomb or reticulation pattern on chest HRCT (95% CI1.34–10.17) (S3 Table). In addition to interstitial lung disease, a correlation betweenSAA levels and mean pulmonary artery pressure was also noted (r = 0.275, n = 33, p =0.12) (Fig. 2C). This correlationbecame even stronger (r = 0.702, n = 11, p = 0.02) in Scl-70 positive patients (r =0.721, n = 11, p = 0.01). Moreover, serum SAA levels positively correlated with serumBNP levels (r = 0.202, n = 122, p = 0.03) (Fig. 2D).


Serum amyloid A is a marker for pulmonary involvement in systemic sclerosis.

Lakota K, Carns M, Podlusky S, Mrak-Poljsak K, Hinchcliff M, Lee J, Tomsic M, Sodin-Semrl S, Varga J - PLoS ONE (2015)

SAA levels are correlated with pulmonary function.Correlation between serum levels of SAA and pulmonary function tests (A, B);pulmonary artery pressure (C); serum BNP levels (D). The horizontal linerepresents the SAA cut-off (19.5μg/ml) and vertical line cut-off forpulmonary arterial hypertension (right heart catheterization mPAO≥25mmHg). Spearman correlation coefficient (r), p value, and number of patients(n) are shown.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4321755&req=5

pone.0110820.g002: SAA levels are correlated with pulmonary function.Correlation between serum levels of SAA and pulmonary function tests (A, B);pulmonary artery pressure (C); serum BNP levels (D). The horizontal linerepresents the SAA cut-off (19.5μg/ml) and vertical line cut-off forpulmonary arterial hypertension (right heart catheterization mPAO≥25mmHg). Spearman correlation coefficient (r), p value, and number of patients(n) are shown.
Mentions: Patients with elevated SAA had significantly impaired pulmonary function (Table 2). In particular, SAAlevels were inversely correlated with FVC (r = −0.253, p = 0.01) and DLCO (r =−0.320, p = 0.002) (Fig. 2A and 2B). Moreover,different radiologic patterns of lung involvement were associated with significantdifferences (Kruskal-Wallis χ2df = 3 = 9.23, p = 0.03)in SAA levels (S2Table). Of note, patients with elevated SAA were 6.3 times more likely tohave reduced DLCO (< 70% of predicted; 95% CI 1.36–28.91), and 3.7times more likely to show a honeycomb or reticulation pattern on chest HRCT (95% CI1.34–10.17) (S3 Table). In addition to interstitial lung disease, a correlation betweenSAA levels and mean pulmonary artery pressure was also noted (r = 0.275, n = 33, p =0.12) (Fig. 2C). This correlationbecame even stronger (r = 0.702, n = 11, p = 0.02) in Scl-70 positive patients (r =0.721, n = 11, p = 0.01). Moreover, serum SAA levels positively correlated with serumBNP levels (r = 0.202, n = 122, p = 0.03) (Fig. 2D).

Bottom Line: Elevated levels of SAA were found in 25% of SSc patients, with the highest levels in those with early-stage disease and diffuse cutaneous involvement.Significant negative correlations of SAA were found with forced vital capacity and diffusion capacity for carbon monoxide.Patients with elevated SAA had greater dyspnea and more frequent interstitial lung disease, and had worse scores on patient-reported outcome measures.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia; Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, United States of America.

ABSTRACT
Inflammation in systemic sclerosis (SSc) is a prominent, but incompletely characterized feature in early stages of the disease. The goal of these studies was to determine the circulating levels, clinical correlates and biological effects of the acute phase protein serum amyloid A (SAA), a marker of inflammation, in patients with SSc. Circulating levels of SAA were determined by multiplex assays in serum from 129 SSc patients and 98 healthy controls. Correlations between SAA levels and clinical and laboratory features of disease were analyzed. The effects of SAA on human pulmonary fibroblasts were studied ex vivo. Elevated levels of SAA were found in 25% of SSc patients, with the highest levels in those with early-stage disease and diffuse cutaneous involvement. Significant negative correlations of SAA were found with forced vital capacity and diffusion capacity for carbon monoxide. Patients with elevated SAA had greater dyspnea and more frequent interstitial lung disease, and had worse scores on patient-reported outcome measures. Incubation with recombinant SAA induced dose-dependent stimulation of IL-6 and IL-8 in normal lung fibroblasts in culture. Serum levels of the inflammatory marker SAA are elevated in patients with early diffuse cutaneous SSc, and correlate with pulmonary involvement. In lung fibroblasts, SAA acts as a direct stimulus for increased cytokine production. These findings suggest that systemic inflammation in SSc may be linked to lung involvement and SAA could serve as a potential biomarker for this complication.

Show MeSH
Related in: MedlinePlus