Session Information
Date: Sunday, November 8, 2015
Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment Poster Session I
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: The aim of this study was to examine
whether circulating levels of the pro-inflammatory glycoprotein tenascin-C (TSC) are useful as an
activity-specific or predictive biomarker in SLE.
Methods: Serum TSC levels were determined by ELISA at inception visit in a prospective cohort
of 59 SLE
patients, and in 65 healthy controls (HC). SLE patients were followed for a
median of one year, and disease activity (assessed by SLEDAI-2K), and changes
in glucocorticoids (GC) and immunosuppressants (IS) were serially recorded
every 3-6 months. We examined cross-sectional relationship between serum
concentrations of TSC and SLE status, SLEDAI-2K scores, strata of disease activity, and levels of anti-dsDNA,
anti-nucleosomal antibodies and C3, C4. We also explored the utility of TSC
levels to predict disease flare defined as (i) increase in SLEDAI ≥3, (ii) new/increased GC, and (iii)
new/increased GC or IS.
Results: Baseline characteristics are shown in
table 1. There was no statistical difference in the mean levels of TSC between
all SLE patients and HC. However, in SLE patients with active disease
(SLEDAI≥ 6) the levels of TSC were significantly higher than in HC
(p=0.004) or patients with no/low disease activity (p=0.004). In SLE patients,
TSC levels were significantly associated with the positivity of anti-dsDNA
(p=0.03) and anti-nucleosomal antibodies (p=0.008), and there was a trend to a
positive correlation with SLEDAI (R=0.25, p=0.06) and clinical SLEDAI scores
(R=0.25, p=0.06) – see table 2. Higher baseline levels of serum TSC showed significantly
greater risk of disease flare defined as the need to escalate glucocorticoids
(HR 1.39; 95% CI: 1.11- 1.73, p = 0.004) or any immunosuppressive therapy (HR
1.25, 95% CI: 1.02-1.52, p=0.028). We also conducted a separate analysis in
which serum TSC level was treated as a categorical variable. In accordance
with the result above, the risk of reaching the flare (ii) or (iii) was
significantly higher in the group of patients wither higher TSC levels (see
table 3).
Conclusion: TSC is not
disease-specific, but it seems to indicate the activity of SLE and may predict
the need to escalate immunosuppressive therapy. TSC levels may thus serve as a useful
activity-specific
and predictive biomarker in SLE. Acknowledgements: This study was supported by grant
IgA NT 13707.
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Table 1 Baseline characteristics |
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SLE (n=59) |
Healthy controls (n=65) |
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Female |
n (%) |
55 (93 %) |
45 (69%) |
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Age (years) |
mean (SD) |
44 (16) |
48 (14) |
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Caucasian |
n (%) |
59 (100%) |
65 (100%) |
|
TSC (ng/ml) |
mean (SD) |
533 (193) |
487 (164) |
|
Disease duration (years) |
mean (SD) |
7 (7) |
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|
SLEDAI 2K |
mean (SD) |
3.7 (3.5) |
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|
cSLEDAI-2K (only clinical SLEDAI items) |
mean (SD) |
2.2 (3.0) |
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SLEDAI 2K ≥ 4 |
n(%) |
30 (53 %) |
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TSC (ng/ml) in pts. with SLEDAI 2K ≥ 4 |
mean (SD) |
578 (229) |
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|
SLEDAI 2K ≥ 6 |
n(%) |
19 (33 %) |
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TSC (ng/ml) in pts. with SLEDAI 2K ≥ 6 |
mean (SD) |
634 (255) |
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ANA+ |
n(%) |
54 (95 %) |
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Anti dsDNA + |
n(%) |
22 (38 %) |
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Low complement |
n(%) |
28 (48 %) |
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Anti-nucleosomal + |
n(%) |
25 (46 %) |
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Oral glucocorticoids |
n(%) |
35 (59 %) |
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Immunosuppressants |
n(%) |
15 (25%) |
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Table 2 Cross-sectional associations between serum TSC levels and clinical and laboratory parameters of SLE patients at inception visit (univariate regression analysis)
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Univariate analyses |
Univariate analyses (age and sex adjusted) |
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Variable |
β* (95% CI) |
p value |
β* (95% CI) |
p value |
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SLE patients vs. HC |
46 (-17; 110) |
0.151 |
44 (-24; 112) |
0.205 |
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SLE pts. with SLEDAI ≥ 4 vs. HC |
91 (9; 173) |
0.029 |
87 (-5; 179) |
0.063 |
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SLE pts. with SLEDAI ≥ 6 vs. HC |
147 (50; 245) |
0.004 |
139 (34; 245) |
0.010 |
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SLE pts. with SLEDAI ≥ 4 vs. SLEDAI < 4 |
98 (-3; 199) |
0.058 |
104 (-9; 217) |
0.070 |
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SLE pts. with SLEDAI ≥ 6 vs. SLEDAI < 6 |
153 (50; 256) |
0.004 |
161 (54; 267) |
0.004 |
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SLE patients (categorical variables) |
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Anti-dsDNA IF (positive vs. negative) |
115 (12; 218) |
0.029 |
112 (3; 221) |
0.044 |
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Anti-nucleosomal (positive vs. negative) |
138 (38; 238) |
0.008 |
131 (30; 234) |
0.013 |
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Complement C3/C4 (low vs. normal) |
-4 (-107; 99) |
0.938 |
-14 (-123; 94) |
0.793 |
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SLE patients (continuous variables) |
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SLEDAI-2K |
14 (-1; 29) |
0.061 |
14 (-1.5; 30) |
0.074 |
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cSLEDAI-2K (only clinical SLEDAI items) |
16 (-1; 33) |
0.060 |
16 (-1.0; 34) |
0.065 |
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C3 (g/l) |
-9 (-209; 192) |
0.931 |
5 (-205; 216) |
0.958 |
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C4 (g/l) |
-232 (-695; 230) |
0.319 |
-210 (-694; 273) |
0.386 |
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Anti-nucleosomal (units) |
-0.2 (-0.7; 0.3) |
0.403 |
-0.2 (-0.7; 0.3) |
0.460 |
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Anti-dsDNA (titre) |
27 (-22; 75) |
0.266 |
30 (-21; 81) |
0.230 |
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The regression coefficient β corresponds to the difference in TSC levels between groups (when assessing categorical variables) or to the change in TSC associated with a 1 unit increase in the assessed variable (when assessing continuous variables). HC = Healthy control. |
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Table 3 Performance of baseline TSC levels to predict disease flares (cox proportional hazard analysis)
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Flare definition |
Univariate analyses |
Univariate analyses (age and sex adjusted) |
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Tenascin as continuous variable |
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HR* (95% CI) |
p value |
HR* (95% CI) |
p value |
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Increase in SLEDAI ≥3 |
1.19 (0.87; 1.63) |
0.277 |
1.21 (0.86; 1.68) |
0.270 |
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New/increased GC |
1.39 (1.11; 1.73) |
0.004 |
1.37 (1.11; 1.70) |
0.004 |
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New/increased GC or IS |
1.25 (1.02; 1.52) |
0.028 |
1.23 (1.01; 1.49) |
0.035 |
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Tenascin as categorical variable (> 659 ng/ml) * |
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Increase in SLEDAI ≥3 |
1.42 (0.28; 7.21) |
0.672 |
1.52 (0.27; 8.64) |
0.636 |
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New/increased GC |
3.77 (1.60; 8.88) |
0.002 |
3.57 (1.48; 8.59) |
0.005 |
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New/increased GC or IS |
2.45 (1.10; 5.46) |
0.028 |
2.23 (0.98; 5.08) |
0.056 |
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* The threshold value of 659 ng/ml for TSC was generated using ROC analysis of relationship between active SLE (SLEDAI≥ 6) and baseline TSC. GC = glucocorticoid. IS = immunosuppressant. |
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To cite this abstract in AMA style:
Zavada J, Uher M, Svobodova R, Olejarova M, Husakova M, Ciferska H, Hulejova H, Senolt L, Vencovsky J. Serum Levels of Tenascin-C Discriminate Patients with Active SLE from Inactive Patients and Healthy Controls, and Predict the Need to Escalate Immunosuppressive Therapy [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/serum-levels-of-tenascin-c-discriminate-patients-with-active-sle-from-inactive-patients-and-healthy-controls-and-predict-the-need-to-escalate-immunosuppressive-therapy/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-levels-of-tenascin-c-discriminate-patients-with-active-sle-from-inactive-patients-and-healthy-controls-and-predict-the-need-to-escalate-immunosuppressive-therapy/