Page 177 - Haematologica-5

MicroRNAs as antiphospholipid syndrome biomarkers
Table 1. Clinical and laboratory parameters of the antiphospholipid syndrome (APS) patients and the healthy donors (HDs).
Females/males
Age, years
Arterial thrombosis
Venous thrombosis
Recurrences
Pregnancy morbidity
Pathological CIMT
APS (total n. 90)
48/42
51.2 ± 13.1
35/90
55/90
37/90
23/90
24/90
1.3 ± 0.11
1.27 ± 0.11
85/90
23.4 (0.5-448)
21.8 (0-354)
23.9 (0-361)
14.8 (0-289)
30/90
62/90
191.7 ± 32.06
51.09 ± 12.4
112.1 ± 33.2
155.1 ± 163.2
13.5 ± 13.6
HDs P (total n. 42)
22/20
46.2 ± 13.4 NS 0/42
0/42
0/42
0/42
6/42 0.00
1.2 ± 0.09 0.02 1.2 ± 0.09 0.02 0/42 0.00 1.3 (0.5-5) 0.00 4.9 (0.8-17) 0.00 1 (1-2) 0.02 1.2 (1-2.6) 0.02
0/42
0/42
190 ± 41.8 NS 55.4 ± 13.1 NS
118.4 ± 26.9 NS 88.3 ± 50.07 NS 6.6 ± 4 0.05
ABI – left*
ABI – right*
LA positivity
aCL-IgG# GPL
aCL-IgM# MPL
Anti-β2GPI IgG#
SGU SMU
Antiplatelet agents†
Anticoagulant agents‡
Total cholesterol level,* mg/dL
Cholesterol HDL level,* mg/dL
Cholesterol LDL level,* mg/dL
Triglycerides level,* mg/dL
ESR,* mm/h
Anti-β2GPI IgM#
n: number; NS: not significant; CIMT: carotid intima-media thickness; ABI: ankle brachial index; LA: lupus anticoagulant; aCL: anti-cardiolipin antibodies; GPL: IgG phospholipid units; MPL: IgM phospholipid units; anti-β2GPI: anti-β2 glycoprotein 1 antibodies; SGU: stantard IgG units; SMU: standard IgM units; HDL: high-density lipoprotein; LDL: low-density lipoprotein; ESR: erythrocyte sedimentation rate. *Results expressed as mean±Standard Deviation. #Results expressed in mean and values range. †Antiplatelet agents include acetylsalicylic acid and clopidogrel. ‡Anticoagulant agents indicate vitamin K antagonists, including warfarin and acenocumarol.
bodies (aCL), anti-β2-glycoprotein 1 antibodies (anti- β2GPI) and/or lupus anticoagulant (LA). Cardiac, cerebral and vascular strokes in these patients are responsible for a significant reduction in life expectancy.1 The course of car- diovascular disease (CVD) in APS patients may rapidly change from asymptomatic to severe life-threatening manifestations that are difficult to deal with. Timely diag- nosis and accurate monitoring of the course of APS are essential to improve the quality of therapy and avoid approaches based on medical empirical protocols. In the same way, like many other autoimmune diseases, APS is a heterogeneous entity, and this has a dramatic impact on diagnosis and treatment.2
Understanding of the pathophysiological mechanisms explaining how atherosclerosis and CVD are associated to APS has been greatly broadened with the application of genomic technologies.3 One emerging and important mechanism controlling gene expression is epigenetics, which regulates gene packaging and independent expres- sion of alterations in the DNA sequence. Epigenetics, which comprises DNA methylation, histone modifica- tions, and microRNAs (miRNAs) activity, is providing new directions linking genomics and environmental fac- tors.4 miRNAs are small, non-coding RNAs that, depend- ing upon base pairing to messenger RNA (mRNA), medi- ate mRNA cleavage, translational repression or mRNA destabilization. miRNAs are known to be involved in cru- cial cellular processes and their dysregulation has been described in many cell types and fluids in a broad range of diseases.5-7
In the setting of APS, a previous study by our group recognized that aPL modulate the expression of 2 miRNAs in monocytes (miR-19b and miR-20a) that con- trol the expression of key proteins involved in the pathology of the disease, such as tissue factor (TF).8 Moreover, we recently demonstrated that both aPL and the anti-double stranded DNA antibodies (anti-dsDNA) promote specific changes in the expression of proteins related to the biogenesis of miRNAs in leukocytes of APS and systemic lupus erythematosus (SLE) patients, which are translated in the altered expression of the miRNAs profile and that of their protein targets (related to CVD) in these disorders.9
Extensive analyses have shown that miRNAs are released into the circulation where they are present in con- centration levels that differ between healthy subjects and patients. Although little is known about the origin and function of such circulating miRNAs, these molecules are increasingly recognized as non-invasive and readily acces- sible biomarkers for risk stratification, diagnosis and prog- nosis of multiple forms of CVD.10
Specific profiles of circulating miRNAs are also associat- ed to the pathophysiology of different systemic autoim- mune diseases, including SLE, systemic sclerosis, and rheumatoid arthritis (RA), and some of them appear to be of diagnostic and, possibly, of prognostic value.11 To date, in the context of APS, no study has analyzed the potential role of the circulating miRNAs as biomarkers of the dis- ease. Therefore, the present study was designed to deter- mine the plasma miRNA specific profile of APS patients,
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