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Abstract Number: 2065

Verification of Novel Soluble Biomarkers That Differentiate Patients with Psoriatic Arthritis from Those with Psoriasis without Psoriatic Arthritis

Vinod Chandran1, Daniela Cretu2,3, Lisa Gao4, Kun Liang4, Antoninus Soosaipillai3 and Eleftherios Diamandis2,3,5, 1Rheumatology, University of Toronto, Toronto Western Hospital, Toronto, ON, Canada, 2Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada, 3Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada, 4Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, ON, Canada, 5Department of Clinical Biochemistry, University Health Network, Toronto, ON, Canada

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Biomarkers, Diagnostic Tests, psoriasis, Psoriatic arthritis and spondylarthritis

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Session Information

Date: Monday, November 9, 2015

Title: Spondylarthropathies and Psoriatic Arthritis - Clinical Aspects and Treatment: Clinical Aspects

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose:
There is a high prevalence of undiagnosed psoriatic arthritis (PsA) in
psoriasis patients. Therefore identifying soluble biomarkers for PsA will help
in screening psoriasis patients for appropriate referral to a rheumatologist.
Our purpose was to investigate whether serum levels of novel markers discovered
by quantitative mass spectrometry (MS) of synovial fluid and skin biopsies,
differentiate PsA patients from those with psoriasis without PsA (PsC).

Methods: Serum
samples were obtained from 100 patients with PsA, 100 with PsC, and 100 healthy
controls. Subjects were group matched for age and sex. No patient was
undergoing treatment with biologics at the time of serum collection. Using
enzyme-linked immunosorbent assays, four high-priority markers, previously
discovered by quantitative MS of synovial fluid and skin biopsies, were
analyzed in the serum: Mac-2-binding protein (M2BP), CD5-like protein (CD5L),
Myeloperoxidase (MPO), and Integrin-β 5 (ITGB5), as well as previously
established markers Matrix metalloproteinase-3 (MMP3) and C-reactive protein
(CRP). Data were analyzed using logistic regression (LR), and receiver
operating characteristic (ROC) curves were plotted.

Results: The 100
PsA patients (41 females, mean age 51 years) had mean psoriasis duration of
22.9 years, PsA duration of 14.6 years, swollen joint count 3.2, tender joint count 6, and PASI score of 4.7. The 100 PsC
patients (45 females, mean age 50 years) had mean psoriasis duration of 20.3
years and PASI score of 4. The 100 controls (52 females) had a mean age of 35 years. Polychotomous LR (Table 1) showed
that ITGB5, CRP and M2BP are markers that are significantly different between
the three groups. The analyses also showed that CD5L, ITGB5, M2BP, MPO, MMP3
and CRP are independently associated with PsA, while CD5L, M2BP and MPO are
independently associated with PsC.  When comparing PsA to PsC, ITGB5, M2BP, and
CRP were found to be independently associated with PsA (Table 2). ROC analysis (Figure
1) of this model showed an area under the ROC curve of 0.85 (95% CI [0.80, 0.90]).

Conclusion: CD5L,
ITGB5, M2BP, MPO, MMP3 and CRP are soluble PsA markers. However, only ITGB5,
M2BP and CRP, differentiate PsA from PsC.

Table 1. Polychotomous logistic regression analysis to identify biomarkers associated with PsA and PsC

PsA

PsC

Biomarkers

Homogeneity P-valuea

ORb (95% CI)

P-valuec

ORb (95% CI)

P-valuec

CD5L, ng/mL

5.48E-01

1.67 (1.28, 2.17)

1.49E-04

1.57 (1.25, 1.97)

8.71E-05

ITGB5, ng/mL

1.18E-05

3.23 (1.98, 5.27)

2.88E-06

1.21 (0.89, 1.64)

2.14E-01

M2BP, ng/mL

1.97E-03

151.73 (19.64, 1172.19)

1.48E-06

9.19 (2.47, 34.25)

9.38E-04

MMP3, ng/mL

1.72E-01

1.79 (1.05, 3.06)

3.18E-02

1.39 (0.86, 2.26)

1.81E-01

MPO, ng/mL

5.33E-01

2.36 (1.50, 3.72)

1.97E-04

2.64 (1.75, 3.98)

3.27E-06

CRP, mg/L

1.40E-06

2.36 (1.67, 3.33)

9.93E-07

1.16 (0.91, 1.47)

2.28E-01

aIndicates whether the markers have significantly different effects when modeling PsA and PsC separately, and controlling for age, sex, and the other biomarkers listed.

bOdds ratio- indicates OR associated with a two-fold increase in the protein level

cIndicates the significance of difference between PsA or PsC, and controls.


Table 2. Logistic regression analysis comparing patients with PsA to PsC

Univariate

Multivariate

Biomarkers

ORa (95% CI)

P-value

ORa (95% CI)

P-value

CD5L, ng/mL

1.08 (0.92, 1.26)

3.63E-01

–

–

ITGB5, ng/mL

4.07 (2.44, 6.81)

8.36E-08

3.82 (2.18, 6.70)

3.05E-06

M2BP, ng/mL

29.72 (5.88, 150.09)

4.05E-05

32.32 (4.90, 213.32)

3.07E-04

MMP3, ng/mL

1.59 (1.21, 2.11)

1.00E-03

–

–

MPO, ng/mL

1.09 (0.83, 1.43)

5.40E-01

–

–

CRP, mg/mL

1.93 (1.50, 2.48)

2.55E-07

1.96 (1.46, 2.62)

5.84E-06

aOdds ratios associated with a two-fold increase in the protein level

Figure 1. ROC curve showing the AUC for the logistic regression model comparing
PsA, to PsC patients.


Disclosure: V. Chandran, AbbVie, 2; D. Cretu, None; L. Gao, None; K. Liang, None; A. Soosaipillai, None; E. Diamandis, None.

To cite this abstract in AMA style:

Chandran V, Cretu D, Gao L, Liang K, Soosaipillai A, Diamandis E. Verification of Novel Soluble Biomarkers That Differentiate Patients with Psoriatic Arthritis from Those with Psoriasis without Psoriatic Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/verification-of-novel-soluble-biomarkers-that-differentiate-patients-with-psoriatic-arthritis-from-those-with-psoriasis-without-psoriatic-arthritis/. Accessed .
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