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Abstract Number: 1023

Tumor Necrosis Factor-a (TNF-a) and Interferon Gamma Inducible Protein-10 (IP-10) As Predictors of Active Disease Status in Localized Scleroderma

Kathryn S. Torok1, Jonathan Yabes2, Qi Mi3, Christina Kelsey1 and Kelsey Magee4, 1Pediatric Rheumatology, Univ of Pittsburgh Med Ctr, Pittsburgh, PA, 2Department of Medicine, University of Pittsburgh, Pittsburgh, PA, 3Department of Sports Medicine and Nutrition, University of Pittsburgh, Pittsburgh, PA, 4Pediatrics, University of Pittsburgh, Pittsburgh, PA

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Biomarkers, cytokines, Morphea, pediatric rheumatology and scleroderma

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Session Information

Date: Sunday, November 8, 2015

Session Title: Pediatric Rheumatology - Pathogenesis and Genetic

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose:   Localized
scleroderma has both inflammatory and fibrotic components contributing to its
effect on the skin and underlying tissue.   The extent and duration of
inflammation during the active phase of the disease is thought to be the major
contributor to long-term disease damage and disability in LS.  Therefore, accurately
identifying the active disease state is imperative, which may not always be
apparent in subtypes with deeper tissue involvement or slowly progressive
changes, such as with the Parry Romberg subtype.  Current commercially
available serological markers of disease activity, such as ESR and CRP, are
rarely elevated in LS.  Therefore, identifying new circulating biologic markers
reflecting active disease status would be helpful for patient management;
especially when deciding when to initiate or discontinue therapy in unclear
cases. 

Methods:   Forty-five LS subjects
with ≥ 2 serial serum samples who had active disease (Physician Global
Assessment – Activity > 0) at the first sera collection and had subsequently
entered inactive disease state at follow-up (remission) were included in a 31
cytokine/chemokine Luminex panel (TH1 / 2 / 17 associated panels)
run on 72 total LS subjects.   The cytokine profile of active vs. inactive
disease state was analyzed utilizing both statistical modeling and data mining
techniques.  Unadjusted and adjusted mixed effects logit models were fitted
using activity status as the outcome and each of the cytokines as the primary
predictor. Covariates for adjustment were included one at a time. Cytokine
levels were categorized into quartiles and Association Rules Mining (web-based
analyses) and Bayesian Network assessment were used as alternative analytical
strategies. 

Results:   In unadjusted analyses,
the cytokines/chemokines that were significantly elevated at the baseline
active disease visit compared to the inactive disease state at follow-up were
IP-10 (Odds Ratio (OR) [95% confidence interval] = 2.1 [1.4, 3.2], p
<0.001), TNF-α (OR = 1.8 [1.1, 3.0], p = 0.016), and MCP-1 (OR =
2.0 [1.1, 3.9], p = 0.034).  After adjusting one at a time for several
clinical covariates, such as age at first sample, disease duration, gender, mLoSSI,
LoSDI, ANA, Anti-ssDNA and AHA antibodies, IP-10 remained significant for all
adjustments, TNF-α significant for all except mLoSSI, and MCP-1
significant for all except disease duration.  Data mining approaches
demonstrated similar results with elevation of IP-10 and TNF-α in the
peripheral blood (4th quartile) showing the strongest links in the
active disease node, followed by other TH1 associated cyto/chemokines
and TH17 associated cytokines.

Conclusion:   IP-10 and TNF-α
were identified as inflammatory mediators that predict disease activity when
comparing paired active and inactive LS serologic cytokine/chemokine profiles. 
These data support earlier findings of correlations of IP-10 and TNF-α
with disease activity parameters in a cross-sectional Luminex plasma study. 
These may serve to augment clinical decision making when disease activity
status is not straightforward by clinical examination.  Further study with
additional longitudinal serological data points is underway.


Disclosure: K. S. Torok, None; J. Yabes, None; Q. Mi, None; C. Kelsey, None; K. Magee, None.

To cite this abstract in AMA style:

Torok KS, Yabes J, Mi Q, Kelsey C, Magee K. Tumor Necrosis Factor-a (TNF-a) and Interferon Gamma Inducible Protein-10 (IP-10) As Predictors of Active Disease Status in Localized Scleroderma [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/tumor-necrosis-factor-a-tnf-a-and-interferon-gamma-inducible-protein-10-ip-10-as-predictors-of-active-disease-status-in-localized-scleroderma/. Accessed January 27, 2021.
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