The Relationship Between Vascular Biomarkers and Disease Characteristics in Systemic Sclerosis: Elevated MCP-1 Is Associated with Predominantly Fibrotic Manifestations

Yasemin Yalcinkaya¹, Suzan Cinar², Sevil Kamali¹, Lale Ocal¹, Gunnur Deniz² and Murat Inanc³, ¹Istanbul Medical Faculty, Department of Internal Medicine, Division of Rheumatology, Istanbul University, Istanbul, Turkey, ²DETAE, Istanbul University, Istanbul, Turkey, ³Division of Rheumatology, Department of Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Biomarkers and systemic sclerosis

Session Information

Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's - Pathogenesis, Animal Models and Genetics

Session Type: Abstract Submissions (ACR)

Background/Purpose: To determine the relationship between vascular biomarkers reflecting the vascular injury and organ involvement in systemic sclerosis (SSc).

Methods : Seventy–two SSc patients (66 female) fulfilling 2013 ACR/EULAR Criteria were evaluated. Serum samples of patients were collected for flow–cytometric analysis of CD40L, tPA, MCP-1, sE–selectin, IL-8, IL-6, VEGF, sP–selectin, TGF-β1 and VCAM levels (Bender MedSystems) in SSc patients and 20 healthy controls. Results were compared with Pearson chi–square / Fischer’s and Mann Withney tests.

Results: The mean age of the patients was 44.9 and disease duration from the appearance of first non–Raynaud symptom was 3.2±2.4 years. Of the patients 23 (32%) had diffuse and 49 (68%) limited cutaneous involvement, 15 (21%) were anti-centromere (+) and 34 (47%) were anti-Scl70 (+). In SSc patients, levels of tPA (p=0.02), MCP-1 (p=0.001), sE–selectin (p=0.008), TGF-β1 (p=0.001) were significantly higher, sP–selectin (p=0.011) and IL-8 (p=0.001) were lower than healthy controls (table-1).

Table-1: Vascular Biomarkers in Healthy Controls and Systemic Sclerosis

*Biomarker* *Levels (mean±SD)*	Healthy Controls (n=20)	Systemic Sclerosis (n=72)
sCD40L (pg/ml)	24620±13051	27847±33315
tPA (pg/ml)	2415±1279	4036±6961*
MCP-1 (pg/ml)	907±300	1302±550**
sE–selectin (ng/ml)	205±78	269±106**
IL-8 (pg/ml)	49±73**	22±80
IL-6 (pg/ml)	0	0.6±2.8
VEGF (pg/ml)	704±363	776±591
sP–selectin (ng/ml)	364±137*	287±86
TGF-β1 (pg/ml)	2421±4785	8277±8592**
VCAM (pg/ml)	3231±1435	3945±1754

*p<0.05, **p<0.01 When healthy controls and sytemic sclerosispatients were compared with Mann–Whitney test

Levels of MCP-1 was elevated in patients with dcSSc, flexion contractures, FVC<80%, DLCO<80%, pulmonary fibrosis and high acute phase response (p=0.002, p=0.005, p=0.045, p=0.005, p=0.036, p=0.006, respectively), TGF-β1 in patients under immunosupressives (p=0.001), sE–selectin in patients with high acute phase response (p=0.028), sCD40L in patients with smoking habitus (p=0.032) and lcSSc (p=0.011) (table-2).

Table-2: Vascular Biomarkers between disease characteristics of Systemic Sclerosis Patients

MCP-1

(pg/ml)

sCD40L

(pg/ml)

sE–selectin (ng/ml)

TGF-β1 (pg/ml)

Skin Involvement –diffuse

–limited

+ (n=23)

+ (n=49)

1586±579** 1169±486

18494±20360

32238±37284*

285±107

262±106

9544±8864

7683±8489

Flexion Contractures

+ (n=12)

– (n=60)

1757±646** 1211±485

16768±13118

30064±35687

279±129

267±102

9068±6873

8119±8937

Low DLCO (<80%)

+ (n=28)

– (n=44)

1548±654** 1145±407

34841±49690

23397±15170

274±116

266±100

9832±8785

7288±8418

Low FVC (<80%)

+ (n=19)

– (n=53)

1537±618* 1218±503

23374±21490

29452±36683

267±104

270±108

10558±8604

7460±8520

Pulmonary Fibrosis

+ (n=18)

– (n=54)

1526±558* 1228±531

26309±21268

28361±36615

287±89

263±111

8831±9385

8093±8397

High Acute Phase Response

+ (n=30)

– (n=42)

1543±621** 1137±424

27581±20414

28522±40715

300±95* 247±110

9219±8522

7790±8704

Smoking History

+ (n=32)

– (n=40)

1233±514

1358±576

36878±45771

20624±15326

281±104

260±108

7627±9047

8798±8290

Immunosuppressives

+ (n=41)

– (n=31)

1345±547

1246±557

24497±19379

32279±45720

270±110

268±102

10981±9057*

4702±6493

*p<0.05, **p<0.01 When groups were compared with Mann–Whitney test

MCP-1 and sE–selectin levels were correlated with disease activity (r=0.243, p=0.040 and r=0.303, p=0.010) (Valentini et al.)

Conclusion : MCP-1, t-PA, TGF-β1, sE–Selectin, sP–Selectin and IL-8 were differently regulated in SSc patients. MCP-1 was the prominently biomarker correlated with manifesatations related to fibrosis and may be a surrogate marker for fibrotic disease activity. Treatment and smoking may have an effect on cytokine profile. Vascular biomarkers can be used to predict the characteristics and severity of SSc warranting prospective studies.

Disclosure:

Y. Yalcinkaya,
None;

S. Cinar,
None;

S. Kamali,
None;

L. Ocal,
None;

G. Deniz,
None;

M. Inanc,
None.

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