Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Is Surfactant D or CC-Chemokine Ligand 18 Biomarkers for Interstitial Lung Disease in Systemic Sclerosis?

Assassi2,  Shervin, Charles3,  Julio, Arnett7,  Frank C., Sharif2,  Roozbeh, Lasky3,  Robert E., Gonzalez5,  Emilio B., Draeger4,  Hilda T.

Eli Lilly and Co, Indianapolis, IN
Univ of Texas Health Science Center at Houston, TX
Univ of Texas Health Science Center at Houston
Univ of Texas Health Science Center at San Antonio, San Antonio, TX
Univ of Texas Medical Branch Galveston, TX
University of Texas-Houston, TX
UT Medical School, Houston, TX

Objective:

Previous studies have indicated that surfactant D (SP-D) levels correlate with the presence of interstitial lung disease (ILD) in patients with systemic sclerosis (SSc).

CC-chemokine ligand 18 (CCL18) is a chemokine produced by activated macrophages that upregulates collagen production in lung fibroblasts. Previous studies have suggested that CCL18 predicts the change in forced vital capacity (FVC) in patients with idiopathic pulmonary fibrosis.

Our goal was to investigate the predictive significance of SP-D and CCL18 for the decline rate in FVC over time in a large prospective cohort of SSc patients.

Methods:

SP-D and CCL18 levels were determined in 266 SSc patients and 100 age, ethnicity and gender matched unaffected controls using commercially available ELISA kits. The SSc plasma samples were collected at the initial visit of the Genetics versus Environment in Scleroderma Outcome Study (GENISOS), an observational cohort of patients with early SSc. Pulmonary function tests (PFT) were obtained at the initial visit and annually thereafter. The primary outcome was FVC expressed as a percentage of predicted value. First, the protein levels between patients and controls were compared by t-test. Subsequently, the correlation of protein levels with the FVC at the enrollment visit was investigated by linear regression. Finally, a generalized linear mixed model with the sequentially obtained FVCs as the outcome variable was utilized for the longitudinal analysis. The predictive value of SP-D and CCL-18 for the decline rate in FVC was investigated by the interaction term between the protein levels and follow up time. The protein levels were examined as continuous variable as well as a dichotomized variable according to the 95th percentile level in controls.

Results:

The average disease duration at enrollment was 2.5 years. 156 patients (59%) had diffuse cutaneous involvement. The mean follow up time in the study was 3.8 years. 926 FVC measurements belonging to 244 patients fulfilled the American Thoracic Society criteria and were included in the analysis.

SP-D levels were significantly higher in SSc patients than controls (p=0.001, mean difference= 643.9, CI= 256–1031.8). Furthermore, the SP-D level correlated with the FVC levels at enrollment (p=0.008, R2=0.033). However, the SP-D did not predict the decline rate in FVC over time (p=0.649). Similarly, the dichotomized value of SP-D (based on 95th percentile in controls) did not predict the rate of decline in FVC (p=0.195).

CCL18 levels did not differ significantly between patients and controls (p=0.212, mean difference=7.4, CI=- 4.3– 19.1). The CCL18 did not correlate with the FVC at enrollment (p=0.21). Furthermore, CCL18 did not predict the decline rate in FVC over time as a continuous or dichotomized variable (p=0.439 and p=0.212, respectively).

A repeat analysis after adjustment for smoking status showed similar results for both proteins.

Conclusion:

Although SP-D correlates with the concomitantly obtained FVC levels, it is not useful as a predictive biomarker for the decline rate in FVC. On the other hand, CCL18 correlates neither with the concomitantly obtained FVC nor with its progression over time in SSc.

To cite this abstract, please use the following information:
Assassi, Shervin, Charles, Julio, Arnett, Frank C., Sharif, Roozbeh, Lasky, Robert E., Gonzalez, Emilio B., et al; Is Surfactant D or CC-Chemokine Ligand 18 Biomarkers for Interstitial Lung Disease in Systemic Sclerosis? [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1218
DOI: 10.1002/art.28984

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