Session Information
Date: Sunday, November 8, 2015
Title: Systemic Sclerosis, Fibrosing Syndromes, and Raynaud's - Clinical Aspects and Therapeutics I
Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: Systemic sclerosis (SSc)
carries high risk for progressive interstitial lung disease (ILD), but
biomarkers for individual risk stratification are largely missing. There is an
ongoing discussion about the potential of chemokine CCL18 or pulmonary and
activation regulated chemokine (PARC) as a marker for (progressive) ILD in SSc.
The
aim of this study was to examine associations between ILD parameters and serum
levels of CCL18 in a large and unselected SSc cohort with complete and data
sets on pulmonary function and lung fibrosis extent by HRCT.
Methods: Sera from the prospective Oslo University Hospital
SSc cohort (n=298) and healthy blood donor controls (HC; n=100) were analysed
for CCL18 by enzyme immunoassay. CCL18
levels were defined as high or low using [mean 2SD] in HC sera as cut-off
value. Paired
pulmonary function tests and HRCT images were obtained at baseline and
follow-up. All patients in the SSc cohort met the 2013 ACR/EULAR classification
criteria.
Results: CCL18
was increased in SSc compared to HC, and high levels of CCL18 (>53 ng/ml)
were identified in 105/298 (35%) of the SSc patients. Patients with high and
low CCL18 did not differ regarding demographics, SSc subtype or auto-antibody
profile (Table 1). Analysis of ILD
parameters showed that high CCL18 was associated with low Forced Vital Capacity
(FVC) at baseline, decline in FVC across the observation period and lung
fibrosis progression; expressed as annual fibrosis progression rate (Table 2).
Multivariate analyses showed associations between CCL18, FVC decline and FVC
<70% at follow up (Table 3). Finally, Kaplan-Meyer analyses showed that
patients with high CCL18 levels had reduced 5-and 10 year survival compared to
the CCL18 low subset; (85% and 74% compared to 97% and 89%, log rank: 0.004).
Conclusion: In this
prospective SSc cohort, high levels of CCL18 were associated with deterioration
of lung function, higher annual fibrosis progression rate and decreased
survival. Our results support the notion that circulating CCL18 has potential
as marker for progressive ILD in SSc.
Table1: Demographics and clinical findings in the SSc cohort stratified
by level of CCL18
|
|
Total SSc cohort (n=298)
|
Low CCL 18 (n=193)
|
High CCL18 (n=105)
|
p-value*
|
|
Age at disease onset, yrs (SD)
|
48 (15.4)
|
47 (15.1)
|
51 (16.6)
|
0.064
|
|
Time disease onset to sampling, yrs (SD)
|
5.9 (6.1)
|
6.4 (6.1)
|
5.2 (6.1)
|
0.111
|
|
Total observation period, yrs (SD)
|
11.5 (8.0)
|
11.7 (7.2)
|
11.2 (9.3)
|
0.635
|
|
Males, no (%)
|
55 (13.8)
|
29 (15.0)
|
26 (24.8)
|
0.038
|
|
Ever smoker, no (%)
|
107 (26.9)
|
71 (39.4)
|
36 (37.5)
|
0.752
|
|
Deceased, no (%)
|
67 (16.8)
|
33 (17.1)
|
34 (32.4)
|
0.003
|
|
Diffuse cutaneous SSc, no (%)
|
78 (19.6)
|
48 (24.9)
|
30 (28.6)
|
0.488
|
|
Pulmonary hypertension, no (%)
|
52 (13.1)
|
25 (13.0)
|
27 (25.7)
|
0.006
|
|
Anti-topoisomerase antibodies, no (%)
|
47 (11.8)
|
27 (15.3)
|
20 (21.1)
|
0.427
|
|
Anti-centromere antibodies, no (%)
|
127 (31.8)
|
83 (46.6)
|
44 (46.3)
|
0.902
|
Tabl2: Lung fibrosis and lung function in the SSc cohort stratified by
level of CCL18
|
|
Total SSc cohort (n=298)
|
Low CCL 18 (n=193)
|
High CCL18 (n=105)
|
p-value*
|
|
Baseline lung fibrosis, % mean SD
|
6.6 (12.7)
|
5.5 (10.5)
|
8.6 (15.8)
|
0.105
|
|
Annual fibrosis progression rate % mean
|
0.5 (2.3)
|
0.2 (1.9)
|
0.9 (2.9)
|
0.028
|
|
Baseline FVC, % mean SD
|
94.7 (20.5)
|
96.6 (19.6)
|
91.2 (21.8)
|
0.031
|
|
Total FVC decline, % mean SD
|
4.3 (13.7)
|
2.4 (10.9)
|
8.0 (17.4)
|
0.004
|
|
FVC >10%, no (%)
|
76 (26.6)
|
36 (19.0)
|
40 (41.2)
|
<0.000
|
|
FVC <70% at follow up, no (%)
|
53 (18.5)
|
25 (13.2)
|
28 (28.9)
|
0.001
|
|
Baseline DLCO, % mean SD
|
68.2 (21.7)
|
71.4 (20.9)
|
62.0 (22.0)
|
<0.000
|
|
DLCO decline, % mean SD
|
8.4 (14.8)
|
8.0 (14.1)
|
9.1 (16.0)
|
0.553
|
|
DLCO decline >15%, no (%)
|
85 (29.9)
|
54 (28.7)
|
31 (32.2)
|
0.535
|
Table 3: Multivariate analyses with FVC <70% at follow up, FVC
decline and annual fibrosis progression rate as primary outcomes
|
|
Primary outcomes
|
|
||||
|
|
FVC <70%
|
p- value
|
FVC decline >10%
|
p- value
|
Annual fibrosis progression
|
p- value
|
|
CCL 18 OR (95% CI)
|
3.8 (1.27-11.55)
|
0.017
|
3.1 (1.66-5.57)
|
<0.001
|
1.7 (0.80-3.71)
|
0.169
|
|
Anti-centromere OR (95% CI)
|
0.3 (0.08-1.09)
|
0.068
|
0.3 (0.19-0.66)
|
<0.001
|
0.49 (0.19-1.19)
|
0.116
|
|
Baseline FVC OR (95% CI)
|
0.9 (0.82-0.91)
|
<0.001
|
0.34 (0.99-1.03)
|
0.057
|
1.01 (0.99-1.04)
|
0.302
|
|
Baseline fibrosis OR (95% CI)
|
1.06 (1.01-1.09)
|
0.050
|
|
|
1.2 (1.08-1.25)
|
<0.001
|
To cite this abstract in AMA style:
Hoffmann-Vold AM, Heiervang Tennøe A, Midtvedt O, Garen T, Lund MB, Aalokken TM, Brunborg C, Ueland T, Molberg . High Levels of CCL-18 Are Associated with Deterioration of Lung Function, Increased Annual Fibrosis Progression Rate and Decreased Survival in Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/high-levels-of-ccl-18-are-associated-with-deterioration-of-lung-function-increased-annual-fibrosis-progression-rate-and-decreased-survival-in-systemic-sclerosis/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/high-levels-of-ccl-18-are-associated-with-deterioration-of-lung-function-increased-annual-fibrosis-progression-rate-and-decreased-survival-in-systemic-sclerosis/