Soluble ST2 and CXCL-10 may serve as biomarkers of subclinical diastolic dysfunction in SLE and correlate with disease activity and damage

Abstract

Objective

Subclinical myocardial dysfunction has been reported to occur early in systemic lupus erythematous (SLE). The study aim was to search for biomarkers of subclinical myocardial dysfunction which may correlate with disease activity in SLE patients.

Methods

This is a prospective, controlled, cross-sectional study of 57 consecutive patients with SLE and 18 controls. Serum samples were obtained to determine serum soluble ST2 (sST2), CXCL-10 and high-sensitivity troponin (hs-troponin) levels. All participants underwent an echocardiographic tissue Doppler study.

Results

sST2, CXCL-10 and hs-troponin levels were higher in patients with higher SLE disease activity (SLEDAI). sST2 and CXCL-10 levels were higher in patients with more disease damage as measured by the SLE damage index. Measures of diastolic dysfunction, as assessed by echocardiographic tissue Doppler negatively correlated with log CXCL-10: including E/A; E/e′_lateral and E/e′_septal, while E/e′ positively correlated with CXCL-10. Diastolic dysfunction parameters also correlated with log sST2 levels, a negative correlation was seen with E/e′_lateral and a positive correlation was seen with E/e′. Systolic dysfunction parameters positively correlated with hs-troponin: LVED, LVES, IVS, LVMASS and LVMASS index. In a multivariate analysis, sST2 and CXCL-10 were found to be significantly different in SLE vs. healthy controls, independent of each other and independent of cardiovascular risk factors.

Conclusions

Soluble ST2 and CXCL-10 are markers of disease activity and accrued damage in SLE and may serve as sensitive biomarkers for detection of subclinical diastolic dysfunction, independent of traditional cardiovascular risk factors.

Keywords

SLE myocardial dysfunction

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References

Rahman

Isenberg

DA.

Systemic lupus erythematosus. N Engl J Med 2008; 358: 929–939.

Moss

Ioannou

Sultan

, et al. Outcome of a cohort of 300 patients with systemic lupus erythematosus attending a dedicated clinic for over two decades. Ann Rheum Dis 2002; 61: 409–413.

Bruce

IN.

Cardiovascular disease in lupus patients: should all patients be treated with statins and aspirin?

Best Pract Res Clin Rheumatol 2005; 19: 823–838.

Schoenfeld

Kasturi

Costenbader

KH.

The epidemiology of atherosclerotic cardiovascular disease among patients with SLE: a systematic review. Semin Arthritis Rheum 2013; 43: 77–95.

Goh

Naidoo

Ngian

GS.

Imaging of systemic lupus erythematosus. Part I: CNS, cardiovascular, and thoracic manifestations. Clin Radiol 2013; 68: 181–191.

Manzi

Meilahn

Rairie

, et al. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham study. Am J Epidemiol 1997; 145: 408–415.

Skaggs

Hahn

McMahon

Accelerated atherosclerosis in patients with SLE–mechanisms and management. Nat Rev Rheumatol 2012; 8: 214–223.

Barutcu

Aksu

Ozcelik

, et al. Evaluation of early cardiac dysfunction in patients with systemic lupus erythematosus with or without anticardiolipin antibodies. Lupus 2015; 24: 1019–1028.

Leal G, Silva K, Lianza A, et al. Subclinical left ventricular dysfunction in childhood-onset systemic lupus erythematosus: a two-dimensional speckle-tracking echocardiographic study. Scandinavian Journal of Rheumatology 2016; 45: 202–209.

10.

Mohammed

Alghamdi

ALjahlan

, et al. Echocardiographic findings in asymptomatic systemic lupus erythematosus patients. Clin Rheumatol 2017; 36: 563–568.

11.

García

Alarcón

Boggio

, et al. Grupo Latino Americano de Estudio del Lupus Eritematoso (GLADEL). Primary cardiac disease in systemic lupus erythematosus patients: protective and risk factors – data from a multi-ethnic Latin American cohort. Rheumatology (Oxford) 2014; 53: 1431–1438.

12.

Kadappu

Thomas

Tissue doppler imaging in echocardiography: value and limitations. Heart Lung Circ 2015; 24: 224–233.

13.

Liu

Kaplan

MJ.

Cardiovascular disease in systemic lupus erythematosus: an update. Curr Opin Rheumatol 2018; 30: 441–448.

14.

Somers

Zhao

Lewis

, et al. Type I interferons are associated with subclinical markers of cardiovascular disease in a cohort of systemic lupus erythematosus patients. PLoS One 2012; 7: e37000.

15.

Frieri

Stampfl

Systemic lupus erythematosus and atherosclerosis: review of the literature. Autoimmun Rev 2016; 15: 16–21.

16.

Bauer

Petri

Batliwalla

, et al. Interferon-regulated chemokines as biomarkers of systemic lupus erythematosus disease activity: a validation study. Arthritis Rheum 2009; 60: 3098–3107.

17.

Schmitz

Owyang

Oldham

, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 2005; 23: 479–490.

18.

Miller

Asquith

, et al. IL-33 reduces the development of atherosclerosis. J Exp Med 2008; 205: 339–346.

19.

Sanada

Hakuno

Higgins

, et al. IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system. J Clin Invest 2007; 117: 1538–1549.

20.

Bartunek

Delrue

Van Durme

, et al. Nonmyocardial production of ST2 protein in human hypertrophy and failure is related to diastolic load. J Am Coll Cardiol 2008; 52: 2166–2174.

21.

Mok

Huang

, et al. Serum levels of IL-33 and soluble ST2 and their association with disease activity in systemic lupus erythematosus. Rheumatology 2010; 49: 520–527.

22.

Divard

Abbas

Chenevier-Gobeaux

, et al. High-sensitivity cardiac troponin T is a biomarker for atherosclerosis in systemic lupus erythematous patients: a cross-sectional controlled study. Arthritis Res Ther 2017; 19: 132.

23.

Tan

Cohen

Fries

, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271–1277.

24.

Bombardier

Gladman

Urowitz

, et al. Derivation of the SLEDAI. A disease activity index for lupus patients. The committee on prognosis studies in SLE. Arthritis Rheum 1992; 35: 630–640.

25.

Gladman

Goldsmith

Urowitz

, et al. The systemic lupus international collaborating clinics/American college of rheumatology (SLICC/ACR) damage index for systemic lupus erythematosus international comparison. J Rheumatol 2000; 27: 373–376.

26.

Quinones

Waggoner

Reduto

, et al. A new, simplified and accurate method for determining ejection fraction with two-dimensional echocardiography. Circulation 1981; 64: 744–753.

27.

Lang

Bierig

Devereux

, et al.; European Association of Echocardiography, European Society of Cardiology. Recommendations for chamber quantification. Eur J Echocardiogr 2006; 7: 79–108.

28.

Zoghbi

Adams

Bonow

, et al. Recommendations for noninvasive evaluation of native valvular regurgitation: a report from the American society of echocardiography developed in collaboration with the society for cardiovascular magnetic resonance. J Am Soc Echocardiogr 2017; 30: 303–371.

29.

Dedeoglu

Şahin

Koka

, et al. Evaluation of cardiac functions in juvenile systemic lupus erythematosus with two-dimensional speckle tracking echocardiography. Clin Rheumatol 2016; 35: 1967–1975.

30.

Shang

Yip

GWK

Tam

, et al. SLICC/ACR damage index independently associated with left ventricular diastolic dysfunction in patients with systemic lupus erythematosus. Lupus 2012; 21: 1057–1062.

31.

Chasset

Arnaud

Targeting interferons and their pathways in systemic lupus erythematosus. Autoimmun Rev 2018; 17: 44–52.

32.

Rönnblom

The importance of the type I interferon system in autoimmunity. Clin Exp Rheumatol 2016; 34: 21–24.

33.

Cacciapuoti

Galzerano

Capogrosso

, et al. Impairment of left ventricular function in systemic lupus erythematosus evaluated by measuring myocardial performance index with tissue doppler echocardiography. Echocardiography 2005; 22: 315–319.

34.

Hardman

Ogg

Interleukin-33, friend and foe in type-2 immune responses. Curr Opin Immunol 2016; 42: 16–24.

35.

Ghali

Altara

Louch

, et al. IL-33 (interleukin 33)/sST2 axis in hypertension and heart failure. Hypertension 2018; 72: 818–828.

36.

Tseng

CCS

Huibers

MMH

Gaykema

, et al. Soluble ST2 in end-stage heart failure, before and after support with a left ventricular assist device. Eur J Clin Invest 2018; 48: e12886.

37.

Tseng

CCS

Huibers

MMH

van Kuik

, et al. The interleukin-33/ST2 pathway is expressed in the failing human heart and associated with pro-fibrotic remodeling of the myocardium. J Cardiovasc Transl Res 2018; 11: 15–21.

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