Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose:
The role of antinucleosome antibodies (ANuA) in the immunopathogenesis of SLE is evident. ANuA was shown to be a good, if not better than anti-dsDNA antibody, diagnostic and prognostic biomarkers in adult SLE pts of different ethnicities. Such evidence is scarce in childhood onset SLE (cSLE). We aim to explore the role of ANuA as potential diagnostic and prognostic biomarker in our ASEAN cohort.
Methods:
68 cSLE pts (onset < 18) were recruited and 55 pts with 180 pt-visits with complete clinical data/blood samples were studied. Disease activity (DA) indices: SLEDAI-2K, SLAM and BILAG were recorded. Anti-dsDNA, ANuA (H1-stripped) and anti-C1q were measured by ELISA. Pts were evaluated at 1-3 mo intervals depending on DA. Pts were grouped into 3 DA groups: no activity (ID), minimal DA (MD) = mild DA with no treatment change or DA with improvement from previous visit and active DA (AD) = new case or flare or persistent DA/refractory to treatment. 72 JIA, 6 JDM, 5 MCTD/UCTD, 11 vasculitides, 5 ANA-positive and 17 other inflammatory conditions composed 116 controls (female 45%, median age (IQR) 13.6 (10.3-16.6)). Descriptive statistics were used to describe data. Mann-Whitney/Kruskal-Wallis tests were used to compare data and Spearman's rho for correlation studies.
Results:
55 cSLE (84% female) with median age of 15.9 (14.4-18.2) and median disease duration of 54.7 (29.4-76.2) mo were included. Majority were Chinese and Malay (38%, 33%). Hematologic disorder (98%), arthritis (58%), malar rash (47%) and renal disease (44%) were among most common manifestations. All cSLE had positive ANA at onset. The median (IQR) of SLEDAI-2K, SLAM and BILAG for each disease activity groups were as follows: ID-2.0 (0.0-2.0), 1.0 (0.0-3.0), 1.0 (0.0-1.0); MD-4.0 (3.0-8.0), 3.0 (2.0-4.0), 2.0 (2.0-4.0) and AD-8.0 (4.0-12.0), 6.0 (3.0-9.0), 5.0 (3.0-12.0). ANuA titers among cSLE disease groups and controls were shown in Figure 1. Diagnostic property and correlation studies were shown in Table 1. ANuA level did not fluctuate with renal DA (p=0.601) or associated with the presence of nephritis (p=0.58), so did anti-dsDNA Ab (p=0.587). ANuA showed good and reasonable diagnostic properties, moderate – strong correlations with laboratory parameters but rather weak correlation with DA indices.
Table 1 Antinucleosome antibodies (ANuA) as diagnostic biomarkers* |
||
Properties |
% |
95% confidence interval |
Sensitivity |
66.67 |
46.04-83.48 |
Specificity |
100.00 |
96.87-100.00 |
+ Likelihood ratio (+LR) |
NA as specificity 100.00%, very large |
|
– Likelihood ratio (-LR) |
0.33 |
0.20-0.57 |
+ Predictive value (+PPV) |
100.00 |
81.47-100.00 |
– Predictive value (-PPV) |
92.80 |
86.77-96.65 |
Diagnostic odd ratio (DOR) |
NA as specificity 100.00%, very large |
|
Antinucleosome antibodies (ANuA) in cSLE and controls |
||
Parameters |
cSLE (n=180)ᵟ |
Controls (n=116) |
ANuA titers (nil < 20 U/ml) |
||
No activity (n=106) ‡ |
3.57 (2.01-30.63) |
1.79 (1.59-1.99) |
Minimal activity (n=23) ‡ |
5.47 (1.83-53.48) |
|
Active disease activity (n=51) ‡ |
24.14 (2.57-129.64) |
|
ANuA and |
Correlation coefficients (rho) |
p value |
ESR |
0.461 |
<0.001 |
CRP |
0.140 |
0.065 |
C3 |
-0.581 |
<0.001 |
C4 |
-0.479 |
<0.001 |
Anti-dsDNA |
0.865 |
<0.001 |
Anti C1q Ab |
0.558 |
<0.001 |
SLEDAI |
0.338 |
<0.001 |
SLAM |
0.188 |
0.012 |
BILAG |
0.074 |
0.324 |
*Controls n=116, cSLE n=27 (20 active disease + 7 newly diagnosed) ‡Minimal activity = mild activity with no therapeutic intervention or activity with improvement from previous visit Active disease activity = New case or flare or persistent activity/ refractory to treatment ᵟpatient-visits |
Conclusion:
ANuA has a good diagnostic property with high specificity and high PPV suggesting that it could be a compliment biomarker in cSLE diagnosis. The levels fluctuated with DA with moderate – strong correlation with lab parameters despite weak correlation with clinical index, for which a larger validation study is needed.
Disclosure:
T. Arkachaisri,
None;
J. G. Yeo,
None;
J. H. T. Tan,
None;
S. F. Hoh,
None;
L. Das,
None;
J. Y. Leong,
None.
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