POS0122 INVESTIGATION OF SERUM MARKER LEVELS IN CONNECTIVE TISSUE DISEASES DEVELOPING ILD

Background

Connective tissue disease (CTD) is an umbrella term for a heterogeneous group of autoimmune diseases affecting the connective tissue in various organs. One of the most serious complications associated with CTDs is interstitial lung disease (ILD), which results in significant morbidity and mortality. A subset of CTD-ILD patients shows progressive disease, which is associated with an even worse prognosis. Previous studies have identified dysregulations of biomarkers including CX3CL1, CCL2, CCL17 and CCL18 in systemic sclerosis (SSc) showing an association with ILD [1-4]. For other CTD-ILD it is less clear, which biomarkers are associated with ILD and ILD progression and few studies have assessed circulating biomarkers across CTD-ILDs.

Objectives

To investigate circulating biomarkers in CTD-ILD and in progressive CTD-ILD patients.

Methods

Serum samples from SSc (n=292), primary sjogrens syndrome (pSS) (n=132), mixed connective tissue disease (MCTD) (n=162), anti-syntetase syndrome (ASS) (n=72) patients and healthy controls (HC) (n=100) collected at Oslo University Hospital (OUH) were analyzed by ELISA for selected biomarkers (CX3CL1, CCL2, CCL17, CCL18). SSc samples were used as the reference disease to compare with mean levels of serum markers in pSS, ASS and MCTD. ILD was diagnosed on high resolution computed tomography (HRCT). Forced vital capacity (FVC) was available at baseline and 12 +/- 3 months. ILD progression defined as an absolute FVC% predicted decline of ≥10% was assessed. Descriptive statistics and logistic regression with odds ratio (OR) and 95%CI were performed.

Results

Serum levels of CX3CL1 and CCL18 were significantly higher in all the CTDs (p<0.001) compared to HC. CCL2 and CCL17 levels were significantly higher in SSc (p=0.001 and p<0.001), ASS (p<0.001 and p=0.004) and MCTD (p<0.001 and p<0.001) compared to HC, but not in pSS (p=0.230 and p=0.087). Of all CTD patients, 267/658 (41%) were diagnosed with ILD (table 1). Of these patients 80 (30%) showed ILD progression, where data were obtained for SSc, pSS and ASS (Tabel 1). All the markers were significantly higher in patients with ILD compared to no ILD in SSc and pSS, while only CCL17 was significantly higher inn ASS-ILD and none in MCTD-ILD. When using SSc-ILD as reference disease, serum levels of CX3CL1 were significantly higher in pSS-ILD (p<0.001) and MCTD-ILD (p<0.001), and CCL18 was significantly lower in MCTD-ILD (p<0.001). Serum levels of CCL2 and CCL17 did not significantly differ between SSc-ILD and the other CTD-ILDs (Figure 1A). From logistic regression analysis of the patient with ILD progression, CCL18 (OR: 1.19, 95%CI, p=0.001) were the only marker significantly associated with ILD progression. When adjusting for CTD with SSc as reference disease, the only marker significantly associated with ILD progression was also here CCL18 (OR: 1.06, 95%CI: 1.03-1.09, p<0.001) (Figure 1B).

Conclusion

In this large CTD cohort, we show that CCL2 and CCL17 are increased across all CTD patients with ILD compared to no ILD, which could help us to identify patients with ILD. ILD progression was only associated with CCL18, which was driven by the SSc-ILD subpopulation.

REFERENCES:

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Acknowledgements:

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Disclosure of Interests

Henriette Didriksen: None declared, Håvard Fretheim Speakers bureau: Boehringer Ingelheim, Consultant of: Bayer, Grant/research support from: GSK/Actelion, Helena Andersson: None declared, Silje Reiseter: None declared, Ragnar Gunnarsson: None declared, Emily Langballe: None declared, Torhild Garen: None declared, Øyvind Midtvedt: None declared, Thor Ueland: None declared, Øyvind Molberg: None declared, Anna-Maria Hoffmann-Vold Speakers bureau: Boehringer Ingelheim, Janssen, Medscape, Merck, Sharp & Dohme and Roche, Consultant of: ARXX, Boehringer Ingelheim, Genentech, Janssen, Medscape, Merck, Sharp & Dohme and Roche, Grant/research support from: Boehringer Ingelheim, Genentech and Janssen.