OP0249 SERUM PROTEOMIC BIOMARKERS DEFINE PATIENTS WITH SYSTEMIC SCLEROSIS WITH INTERSTITIAL LUNG DISEASE
Authors: De Santis M. , Isailovic N. , Ceribelli A. , Motta F. , Vecellio M. , Selmi C. 
Published: May 2021

Background:

Systemic sclerosis (SSc) is a systemic condition affecting multiple organs and thus being burdened by high morbidity and mortality; disease management is based largely on the early detection of organ involvement, particularly in the case of interstitial lung disease (ILD), ideally through noninvasive biomarkers. Beside serum autoantibodies associated with diffuse SSc, there is currently no reliable serum marker to predict the onset of SSc organ involvement, monitor its progression, and foresee the response to treatments. Proteomic analysis based on aptamer technology is a powerful method with the potential to address this unmet need in SSc.

Objectives:

To identify serum biomarkers associated with ILD in SSc.

Methods:

Serum samples from 6 women with SSc (3 with ILD at high-resolution pulmonary CT scan) and 7 age-matched female healthy controls (HC) were analyzed using the SOMAscan platform (SomaLogic, Inc., Boulder, CO, USA) to test more than 1300 proteins even at femtomolar concentration. Subsequent validation of candidate proteins was performed using ELISA in an independent cohort of 88 patients with SSc and 48 HC. Statistical analysis included Student’s t-test and was assessed using the SomaSuite software (SomaLogic, Boulder, CO, USA).

Results:

The proteomic analysis identified 33 proteins with significantly different serum levels in SSc cases compared to HC and 9 proteins differentiating SSc patients according to ILD (Table 1). Compared to HC, SSc sera manifested an altered expression of proteins involved in extracellular matrix formation and cell-cell adhesion (with higher Calpain, EphA5, IDS, MATN2, MMP-12, TNR4, and lower desmoglein-1, SNP25), angiogenesis (with higher anti-angiogenetic factors as angiopoietin-2 and kininogen high molecular weight) lymphocyte recruitment, activation, and signaling (with higher CXCL-1, LAG3 and lower SH21A) with an overall inhibition of neutrophil function (with lower G-CSF-R, CD177, calgranulin B).

Table 1.

Significantly altered proteins at serum proteomic analysis of systemic sclerosis (SSc) with or without interstitial lung disease (ILD) and healthy controls (HC)

SSc versus healthy controlsSSc with ILD versus SSc without ILD and healthy controlsIncreasedReducedIncreasedReducedAldolase A
Angiopoietin-2*
C1QR1
Calpain
COLEC12 Eotaxin
EphA5
Fractalkine/CXCL-1
Granulins
IDS Kininogen, HMV
LAG-3
Lamin-B1
LRP1b
MATN2
MMP-12
STAT1 TMR4Adrenomedullin
ASGR1
C1s
C5
Calgranulin B
CD177
Desmoglein-1
Flt-3 ligand
G-CFS-R
IL-1Ra
Leptin
Lypd3
SH21A
SNP25
TPBS2FCRL3
IL-22BP**
MCP-3
PDE11
PGP9.5
sICAM-5
StratifinBAFF
DERM

*significantly increased also at ELISA

** significantly increased at ELISA only in SSc with ILD versus HC

The majority of proteins with higher levels in SSc with ILD compared to SSc without ILD were involved in intracellular signaling and cell cycle (FCRL3, PDE11, Stratifin), along with higher MCP-3, a monocyte chemoattractant, and sICAM-5, ligand for the leukocyte adhesion protein LFA-1. Of note, we found that increased IL-22BP, antagonist of IL-22, and decreased BAFF levels characterized SSc with ILD.

Conclusion:

Aptamer proteomic analysis allowed to define serum profiles differentiating SSc patients from healthy controls and SSc with ILD from SSc without ILD; the proteins identified are involved in SSc pathogenic pathways and after further investigation on larger cohorts they can be used as reliable biomarkers.

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Disclosure of Interests:

None declared