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Abstract Number: 405

Anti-C1q Antibodies As Potential Diagnostic and Prognostic Biomarkers in Juvenile Systemic Lupus Erythematosus

Thaschawee Arkachaisri1,2, Justin Hung Tiong Tan1, Manasita Tanya1, Sook Fun Hoh3, Lena Das4 and Jing Yao Leong5,6, 1Rheumatology and Immunology, KK Women's and Children's Hospital, Singapore, Singapore, 2Paediatrics, Duke-NUS Graduate Medical School, Singapore, Singapore, 3Nursing, KK Women's and Children's Hospital, Singapore, Singapore, 4Dept of Rheumatology, Cincinnati Children`s Hospital Medical Center, Cincinnati, OH, 5Duke-National University of Singapore Graduate Medical School, Singapore, Singapore, 6SingHealth Translational Immunology and Inflammation Centre, Singapore Health Services Pte Ltd, Singapore, Singapore

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Antibodies, biomarkers and juvenile SLE, Diagnostic Tests, Disease Activity

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Session Information

Date: Sunday, November 8, 2015

Title: Pediatric Rheumatology – Clinical and Therapeutic Aspects Poster I: Lupus, Scleroderma, JDMS

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

Anti-C1q antibodies (AC1q) were
shown to strongly correlate with the occurrence and activity of lupus nephritis
in adult SLE. Data of the antibodies in jSLE are rare. We aim to explore AC1q
role as a diagnostic biomarker and to assess their validity in monitoring jSLE
global disease activity in our Southeast Asian jSLE cohort.

Methods:

Eighty two jSLE patients were
recruited and 72 patients with 517 patient-visits with complete clinical
data/blood samples were studied. Disease activity indices including mS-2K
(SLEDAI without lab), SLAM and BILAG were recorded. Anti-dsDNA, antinucleosome
Abs (ANu, H1-stripped) and aC1q were measured by ELISA. Patients were evaluated
at 1-3 mo intervals depending on their disease severity. Patients were grouped
into 3 disease activity groups: no activity (ID), minimal activity (MD) = mild
activity with no therapeutic intervention or activity with improvement from
previous visit and active disease activity (AD) = new case or flare or
persistent activity/refractory to treatment. 94 JIA, 10 JDM, 12 MCTD/UCTD, 13
vasculitides, 13 ANA-positive and 30 other inflammatory conditions made up 172 controls
(median age (IQR) 14.6 (11.4-17.6) years). Descriptive statistics were used to
describe data. Mann-Whitney/Kruskal-Wallis tests were used to compare data, Spearman’s
rho for correlation and Kaplan-Meier test for time-to-flare studies.

Results:

72 cSLE (81% female) with median
age of 16.5 (14.6-19.0) yrs and median disease duration of 53.1 (26.2-82.4) mo
were included. Chinese (48%) and Malay (28%) were majority. Hematologic disease
(96%), arthritis (56%), malar rash (45%) and renal disease (39%) were among
most common manifestations. All patients had ANA positivity at onset. Fig 1
shows significant differences in AC1q levels between controls vs. jSLE and
among disease activity groups (p < 0.001). Table 1 reveals strong diagnostic
properties of AC1q. The presence of nephritis associated with AC1q (p=0.036).
Correlation analysis showed fair to moderate correlations with ESR, C3, C4,
anti-dsDNA and ANu but weak against clinical indices. AC1q levels increase at
median of 4.8 mo (0-12.83) prior to global disease flare in 64% of visits.

Description: N:Publications2015AbstractsAC1q ACR 2015.jpg

Table 1      Diagnostic properties of Anti-C1q vs. anti-dsDNA antibodies*

 

Anti-C1q antibody

anti-dsDNA antibody

Sensitivity:

0.52 (0.38-0.66)

0.88 (0.98-0.93)

Specificity:

0.98 (0.95-0.99)

0.99 (0.96-0.99)

Positive likelihood ratio:

29.86 (9.42-94.69)

114.63 (16.24-809.23)

Negative likelihood ratio:

0.49 (0.36-0.66)

0.13 (0.07-0.23)

Positive predictive value

0.89 (0.72-0.98)

0.98 (0.93-0.99)

Negative predictive value

0.88 ( 0.83-0.92)

0.94 (0.88-0.97)

Diagnostic odds ratio:

61.23 (17.12-218.98)

910.00 (112.81-7340.94)

*value (95% Confidence Interval)

 

 

Correlation studies comparing anti-C1q and anti-dsDNA antibodies

Correlation coefficients (rho)

Anti-C1q antibodies

n = 237ᵟ

Anti-dsDNA antibody

n = 457ᵟ

rho

p-value

rho

p-value

ESR

0.36

<0.001

0.33

<0.001

C3

-0.34

<0.001

-0.57

<0.001

C4

-0.46

<0.001

-0.51

<0.001

Anti-dsDNA

0.33

<0.001

 

Anti-nucleosome Ab

0.42

<0.001

0.84

<0.001

Anti C1q Ab

 

0.59

<0.001

mS-2K

0.18

0.005

0.19

<0.001

SLAM

0.28

<0.001

0.29

<0.001

BILAG

0.20

0.002

0.20

<0.001

*Controls n=172, cSLE n=72 (35 active disease + 13 newly diagnosed)

ᵟpatient-visits

Conclusion:

Our initial findings showed strong
diagnostic properties of AC1q in our cSLE cohort. The presence of AC1q was
associated with lupus nephritis and its levels seem to fluctuate with global,
if not only renal disease activity. The rise in the levels may signal a flare
in two-third of the jSLE pts. A longer, prospective study is needed to validate
these initial findings in our region.


Disclosure: T. Arkachaisri, None; J. H. T. Tan, None; M. Tanya, None; S. F. Hoh, None; L. Das, None; J. Y. Leong, None.

To cite this abstract in AMA style:

Arkachaisri T, Tan JHT, Tanya M, Hoh SF, Das L, Leong JY. Anti-C1q Antibodies As Potential Diagnostic and Prognostic Biomarkers in Juvenile Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/anti-c1q-antibodies-as-potential-diagnostic-and-prognostic-biomarkers-in-juvenile-systemic-lupus-erythematosus/. Accessed .
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