1. Introduction
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterised by loss of immune cell regulation, chronic inflammation and multiple organ damage. Juvenile-onset disease (JSLE) (onset before 18 years) is a rare condition that occurs in up to 20% of patients and is more severe compared to adult-onset SLE [
1
- Ambrose N
- Morgan TA
- Galloway J
- Ionnoau Y
- Beresford MW
- Isenberg DA.
Differences in disease phenotype and severity in SLE across age groups.
,
2
- Hersh AO
- Trupin L
- Yazdany J
- Panopalis P
- Julian L
- Katz P
- et al.
Childhood-onset disease as a predictor of mortality in an adult cohort of patients with systemic lupus erythematosus.
]. Mortality from SLE has improved dramatically over the last 50 years due mainly to improved treatment [
3
- Bakshi J
- Segura BT
- Wincup C
- Rahman A.
Unmet needs in the pathogenesis and treatment of systemic lupus erythematosus.
]. However, while deaths attributable to active lupus are reduced, deaths associated with comorbidities including cardiovascular disease (CVD) are still high [
4
- Bernatsky S
- Boivin J-F
- Joseph L
- Manzi S
- Ginzler E
- Gladman DD
- et al.
Mortality in systemic lupus erythematosus.
,
5
- Nossent J
- Cikes N
- Kiss E
- Marchesoni A
- Nassonova V
- Mosca M
- et al.
Current causes of death in systemic lupus erythematosus in Europe, 2000—2004: relation to disease activity and damage accrual.
]. CVD risk and mortality are particularly increased in JSLE but this risk can only be partially explained by an increased prevalence of traditional risk factors, suggesting a role for inflammation [
6
- Quinlan C
- Kari J
- Pilkington C
- Deanfield J
- Shroff R
- Marks SD
- et al.
The vascular phenotype of children with systemic lupus erythematosus.
]. It is proposed that all patients with SLE, irrespective of age at disease onset, should receive aggressive monitoring and treatment of modifiable CVD risk factors [
7
- Hersh AO
- Trupin L
- Yazdany J
- Panopalis P
- Julian L
- Katz P
- et al.
Childhood-onset disease as a predictor of mortality in an adult cohort of patients with systemic lupus erythematosus.
], however, no specific guidelines for CVD risk monitoring or management in SLE/JSLE exist. Thus there is an urgent need to find better ways to stratify patients based on their CVD risk and identify adequate therapeutic approaches to decrease the overall cardiovascular morbidity and mortality associated with SLE.
Dyslipidaemia, a conventional risk factor for CVD, is a common feature of patients with both adult and JSLE, and includes elevated triglycerides (TG) and low density lipoprotein (LDL), and reduced high-density lipoprotein (HDL) and apolipoprotein(Apo)-A1 [
8
- McMahon M
- Grossman J
- Skaggs B
- FitzGerald J
- Sahakian L
- Ragavendra N
- et al.
Dysfunctional proinflammatory high-density lipoproteins confer increased risk of atherosclerosis in women with systemic lupus erythematosus.
,
9
- Tyrrell PN
- Beyene J
- Benseler SM
- Sarkissian T
- Silverman ED.
Predictors of lipid abnormalities in children with new-onset systemic lupus erythematosus.
,
10
- Posadas-Romero C
- Torres-Tamayo M
- Zamora-González J
- Aguilar-Herrera BE
- Posadas-Sánchez R
- Cardoso-Saldaña G
- et al.
High insulin levels and increased low-density lipoprotein oxidizability in pediatric patients with systemic lupus erythematosus.
,
11
- Ardoin S
- Sandborg C
- Schanberg L.
Review: management of dyslipidemia in children and adolescents with systemic lupus erythematosus.
,
12
- Borba EF
- Bonfá E
- Vinagre CGC
- Ramires JAF
- Maranhão RC.
Chylomicron metabolism is markedly altered in systemic lupus erythematosus.
]. However, beyond these findings, very little information is available to assess whether defects in lipid metabolism are present in JSLE. Interplay between traditional CVD risk factors (including dyslipidaemia) and risk factors associated with active disease and steroid treatment could contribute to the early, accelerated development of atherosclerosis (chronic inflammation of the large arteries and a major cause of CVD) in JSLE patients [
13
- Schanberg LE
- Sandborg C
- Barnhart HX
- Ardoin SP
- Yow E
- Evans GW
- et al.
Premature atherosclerosis in pediatric systemic lupus erythematosus: risk factors for increased carotid intima-media thickness in the atherosclerosis prevention in pediatric lupus erythematosus cohort.
,
14
- Barsalou J
- Bradley TJ
- Silverman ED.
Cardiovascular risk in pediatric-onset rheumatological diseases.
]. However, despite the favorable effect of hydroxychloroquine treatment on lipid profile and its wide use in lupus [
15
- Cairoli E
- Rebella M
- Danese N
- Garra V
- Borba EF.
Hydroxychloroquine reduces low-density lipoprotein cholesterol levels in systemic lupus erythematosus: a longitudinal evaluation of the lipid-lowering effect.
], the continuing high CVD mortality suggests the need for additional therapies targeting lipid metabolism. Cholesterol-lowering drugs (such as statins, which target cholesterol synthesis) have been trialled in SLE patients with mixed outcomes. Some studies show beneficial effects including improved lipid and inflammatory cytokine levels, reduced vascular inflammation, mortality and morbidity in SLE patients [
16
- Yu H-H
- Chen P-C
- Yang Y-H
- Wang L-C
- Lee J-H
- Lin Y-T
- et al.
Statin reduces mortality and morbidity in systemic lupus erythematosus patients with hyperlipidemia: a nationwide population-based cohort study.
,
17
- Ruiz-Limon P
- Barbarroja N
- Perez-Sanchez C
- Aguirre MA
- Bertolaccini ML
- Khamashta MA
- et al.
Atherosclerosis and cardiovascular disease in systemic lupus erythematosus: effects of in vivo statin treatment.
,
18
- Ardoin SP
- Schanberg LE
- Sandborg CI
- Barnhart HX
- Evans GW
- Yow E
- et al.
Secondary analysis of APPLE study suggests atorvastatin may reduce atherosclerosis progression in pubertal lupus patients with higher C reactive protein.
]. However, in two major randomised control trials, the Lupus Atherosclerosis Prevention Study (LAPS) [
19
- Petri MA
- Kiani AN
- Post W
- Christopher-Stine L
- Magder LS.
] in adults and the Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) trial in children [
20
- Schanberg LE
- Sandborg C
- Barnhart HX
- Ardoin SP
- Yow E
- Evans GW
- et al.
Use of atorvastatin in systemic lupus erythematosus in children and adolescents.
], statins failed to influence atherosclerosis progression. We hypothesised that patient heterogeneity could contribute to the negative results and that the success of future trials could depend on the correct stratification of patients before inclusion into such studies [
21
- van Vollenhoven RF
- Voskuyl A
- Morand E
- Aranow C.
Remission in SLE: closing in on the target.
,
22
Why, why, why de-lupus (does so badly in clinical trials).
] as well as identification of other potential therapeutic targets.
Here, in depth lipoprotein-based metabolomics profiling defined and validated two distinct JSLE patient groups based on their ApoB:ApoA1 ratio, a biomarker previously associated with increased CVD risk [
23
- McQueen MJ
- Hawken S
- Wang XY
- Ounpuu S
- Sniderman A
- Probstfield J
- et al.
Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case-control study.
,
24
- Walldius G
- Jungner I
- Holme I
- Aastveit AH
- Kolar W
- Steiner E.
High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study.
]. Patients with high ApoB:ApoA1 ratios, had a unique immune and transcriptomic signature represented by elevated CD8+ T-cell frequencies, altered expression of genes associated with atherogenic processes including apoptosis, T-cell activation and interferon (IFN) signalling and a more active disease trajectory over time. Collectively, these findings could help identify JSLE patients at greatest CVD risk and select those patients who would benefit from targeted lipid modifying therapies.
4. Discussion
Patients with JSLE have an increased risk of developing CVD. Despite this knowledge, CVD is still the leading comorbidity for patients, highlighting the need for better understanding of the disease process [
2
- Hersh AO
- Trupin L
- Yazdany J
- Panopalis P
- Julian L
- Katz P
- et al.
Childhood-onset disease as a predictor of mortality in an adult cohort of patients with systemic lupus erythematosus.
,
5
- Nossent J
- Cikes N
- Kiss E
- Marchesoni A
- Nassonova V
- Mosca M
- et al.
Current causes of death in systemic lupus erythematosus in Europe, 2000—2004: relation to disease activity and damage accrual.
]. Using metabolomics analysis this study identified ApoB:ApoA1 ratio as a potential predictive biomarker of increased cardiometabolic risk in adolescent patients with JSLE. Patients with high ApoB:ApoA1 ratio shared a serum metabolomic profile with adult SLE patients with sub-clinical atherosclerosis; a CD8+ T-cell phenotype with CD8+ T-cells isolated from human atherosclerotic plaque; and had a more active disease trajectory. Based on these findings we propose that detailed lipoprotein taxonomy analysis could help distinguish JSLE patients with potentially increased CVD risk. This work could both improve clinical trial design and identify patients that could benefit from more tailored disease or lipid-modifying therapy.
Prediction of CVD in the general population predominantly relies on relatively simple measurements such as serum total cholesterol, HDL, LDL and triglycerides [
46
- Sanin V
- Pfetsch V
- Koenig W.
Dyslipidemias and cardiovascular prevention: tailoring treatment according to lipid phenotype.
]. However, more in-depth lipoprotein assessment including lipoprotein subclasses, their lipid concentrations and composition can provide new insights into CVD risk prediction and disease mechanisms [
37
- Holmes MV
- Millwood IY
- Kartsonaki C
- Hill MR
- Bennett DA
- Boxall R
- et al.
Lipids, lipoproteins, and metabolites and risk of myocardial infarction and stroke.
,
47
- Kettunen J
- Demirkan A
- Würtz P
- Draisma HHM
- Haller T
- Rawal R
- et al.
Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA.
,
48
- Ohukainen P
- Kuusisto S
- Kettunen J
- Perola M
- Järvelin M-R
- Mäkinen V-P
- et al.
Data-driven multivariate population subgrouping via lipoprotein phenotypes versusapolipoprotein B in the risk assessment of coronary heart disease.
]. This approach could be particularly relevant for assessing CVD risk in younger patients with chronic inflammatory conditions such as JSLE, for whom the relevance of traditional risk factors in CVD prediction is less robust [
3
- Bakshi J
- Segura BT
- Wincup C
- Rahman A.
Unmet needs in the pathogenesis and treatment of systemic lupus erythematosus.
].
Elevated ApoB:ApoA1 ratio is associated with increased CVD risk in young people. The Cardiovascular Risk in Young Finns Study shows that elevated ApoB and ApoB:ApoA1 ratio and reduced ApoA1 in children and adolescents reflects a predisposition to subclinical atherosclerosis in adulthood in healthy individuals [
49
- Juonala M
- Viikari JSA
- Kahonen M
- Solakivi T
- Helenius H
- Jula A
- et al.
Childhood levels of serum Apolipoproteins B and A-I predict carotid intima-media thickness and brachial endothelial function in adulthood.
]. In support of our study other reports show that ApoB:ApoA1 ratio has an improved CVD predictive value compared to conventional blood cholesterol measures [
23
- McQueen MJ
- Hawken S
- Wang XY
- Ounpuu S
- Sniderman A
- Probstfield J
- et al.
Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case-control study.
,
24
- Walldius G
- Jungner I
- Holme I
- Aastveit AH
- Kolar W
- Steiner E.
High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study.
]; this could be due to the exclusion of VLDL and IDL in the majority of these measures. Our data suggests that converting conventional blood cholesterol measures into ratios could also provide promising biomarkers of CVR in JSLE as they also discriminated between the stratified groups with high performance and have the additional practicality benefit over NMR. There is evidence that ApoA1 and ApoB could be measured in clinical practice facilitated by commercially available colorimetric assays; however, further research is required to compare their performance against NMR spectroscopy. JSLE patients can have reduced ApoA1 and HDL concentration compared with healthy donors [
50
- Machado D
- Sarni ROS
- Abad TTO
- Silva SGL
- Khazaal EJB
- Hix S
- et al.
Lipid profile among girls with systemic lupus erythematosus.
] and adult SLE patients have increased Apo‐B associated with arterial stiffness [
51
- Kwankaew J
- Leelawattana R
- Saignam A
- Siripaitoon B
- Uea-areewongsa P
- Juthong S.
Apolipoprotein B as an independent predictor of arterial stiffness in systemic lupus erythematosus patients.
]. Importantly, we show here that in adolescent JSLE patients, ApoB:ApoA1 ratio statistically significantly correlates with metabolites associated with sub-clinical carotid and/or femoral atherosclerotic plaque in adult SLE patients [
35
- Smith E
- Croca S
- Waddington KE
- Sofat R
- Griffin M
- Nicolaides A
- et al.
Cross-talk between iNKT cells and monocytes triggers an atheroprotective immune response in SLE patients with asymptomatic plaque.
]. We identified a cut-point value for ApoB:ApoA1 ratio of 0.45 that could have clinical utility in JSLE. However, ApoB:ApoA1 ratio is age dependent so further validation of age specific cut points is needed [
37
- Holmes MV
- Millwood IY
- Kartsonaki C
- Hill MR
- Bennett DA
- Boxall R
- et al.
Lipids, lipoproteins, and metabolites and risk of myocardial infarction and stroke.
,
52
ApoB/apoA-I ratio is related to femoral artery plaques in 64-year-old women also in cases with low LDL cholesterol.
,
53
- Morrison JA
- Glueck CJ
- Daniels SR
- Horn PS
- Wang P.
Determinants of ApoB, ApoA1, and the ApoB/ApoA1 ratio in healthy schoolgirls, prospectively studied from mean ages 10 to 19 years: the Cincinnati national growth and health study.
]. Differences in published ratios could be accounted for by different technologies used to assess ApoB and ApoA1 levels (mainly colorimetry-based compared to NMR used here) and the fasting status of the study participants (our study was performed on non-fasting patients). We expect that any longitudinal fluctuations in the ApoB:ApoA1 ratio were due to patient flares, rather than changes in diet or BMI, as this is unlikely to change significantly at 3-month intervals. Importantly, although we adjusted for sex in the metabolomic logistic regression analysis, we identified no statistically significant difference in ApoB:ApoA1 ratio between males and females with JSLE, despite previous reports of sex differences in lipid profile in healthy individuals [
54
- William B.
- Kannel WPC
- Tavia Gordon
- et al.
Serum cholesterol, lipoproteins, and the risk of coronary heart disease.
], reflecting the known increased CVR in young women with SLE. Several studies have shown that sub-clinical atherosclerosis in SLE begins in the rare paediatric age group and highlight the need for paediatric rheumatologists to address modifiable CVR factors in daily practice [
6
- Quinlan C
- Kari J
- Pilkington C
- Deanfield J
- Shroff R
- Marks SD
- et al.
The vascular phenotype of children with systemic lupus erythematosus.
,
20
- Schanberg LE
- Sandborg C
- Barnhart HX
- Ardoin SP
- Yow E
- Evans GW
- et al.
Use of atorvastatin in systemic lupus erythematosus in children and adolescents.
]. However, not all patients with JSLE have the same CVD risk; therefore, identifying patients with a potential low and high CVD risk could be pivotal for the success of anti-CVD interventions. For example, while the APPLE trial of atorvastatin in JSLE patients did not show reduced progression of sub-clinical atherosclerosis overall, a trend towards slower carotid intima-media thickness (CIMT) progression was seen [
20
- Schanberg LE
- Sandborg C
- Barnhart HX
- Ardoin SP
- Yow E
- Evans GW
- et al.
Use of atorvastatin in systemic lupus erythematosus in children and adolescents.
]. The authors suggested certain subgroups of JSLE patients would benefit from targeted statin therapy. Thus, stratifying JSLE patients according to ApoB:ApoA1 ratio could help future clinical trial design to assess efficacy of therapies targeting CVD risk.
JSLE patients with elevated ApoB:ApoA1 ratio were characterised by a distinct CD8+ T-cell immune profile. There was an overlap between CD8+ T-cell DEGs from patients with High ApoB:ApoA1 ratio with those identified in individuals presenting with symptomatic atherosclerotic plaques [
43
- Fernandez DM
- Rahman AH
- Fernandez NF
- Chudnovskiy A
- Amir ED
- Amadori L
- et al.
Single-cell immune landscape of human atherosclerotic plaques.
], helping us to understand the processes involved in the association between High ApoB:ApoA1 ratio and increased CVD risk. CD8+ T-cells are the most abundant cell type in human atherosclerotic plaques (>30%) according to recent single-cell RNA sequencing data, with increased frequency in plaque compared to blood [
43
- Fernandez DM
- Rahman AH
- Fernandez NF
- Chudnovskiy A
- Amir ED
- Amadori L
- et al.
Single-cell immune landscape of human atherosclerotic plaques.
]. However, other studies focusing on CD8+ T-cells in atherosclerosis are limited and conflicting, describing plaque-derived T-cells as either pro- or anti-atherogenic [
55
Protective and pathogenic roles of CD8(+) T cells in atherosclerosis.
,
56
- van Duijn J
- Kritikou E
- Benne N
- van der Heijden T
- van Puijvelde GH
- Kroner MJ
- et al.
CD8(+) T-cells contribute to lesion stabilization in advanced atherosclerosis by limiting macrophage content and CD4(+) T-cell responses.
,
57
Monocyte-macrophages and T cells in atherosclerosis.
,
58
Padgett LE, Dinh HQ, Wu R, Gaddis DE, Araujo DJ, Winkels H, et al. Naive CD8+T Cells expressing CD95 increase human cardiovascular disease severity. Arterioscler Thromb Vasc Biol. 0(0):ATVBAHA.120.315106.
]. Thus, greater understanding of the immune processes leading to human atherosclerotic plaque-development are needed, in particular in the context of chronic inflammation and immune cell dysregulation, which may speed atherosclerosis progression in patients with autoimmune diseases [
42
- Hahn BH
- Grossman J
- Chen WL
- McMahon M.
The pathogenesis of atherosclerosis in autoimmune rheumatic diseases: roles of inflammation and dyslipidemia.
,
59
Mechanisms of disease: atherosclerosis in autoimmune diseases.
,
60
The interplay of inflammation and cardiovascular disease in systemic lupus erythematosus.
].
Notably altered IFN signalling gene expression pathways were shared between peripheral blood CD8+ T-cells from High ApoB:ApoA1 JSLE patients and CD8+ T-cells from symptomatic human plaque. Both Type-I and Type-II IFNs can contribute to atherosclerosis progression [
61
- Chen H-J
- Tas SW
- de Winther MPJ.
Type-I interferons in atherosclerosis.
,
62
Interferon gamma: a master regulator of atherosclerosis.
]. Furthermore, both SLE pathogenesis and SLE sub-clinical CVD are associated with Type-I IFNs [
45
- El-Sherbiny YM
- Psarras A
- Yusof MYM
- Hensor EMA
- Tooze R
- Doody G
- et al.
A novel two-score system for interferon status segregates autoimmune diseases and correlates with clinical features.
,
63
- Somers EC
- Zhao WP
- Lewis EE
- Wang L
- Wing JJ
- Sundaram B
- et al.
Type I interferons are associated with subclinical markers of cardiovascular disease in a cohort of systemic lupus erythematosus patients.
,
64
- Denny MF
- Thacker S
- Mehta H
- Somers EC
- Dodick T
- Barrat FJ
- et al.
Inteirferon-alpha promotes abnormal vasculogenesis in lupus: a potential pathway for premature atherosclerosis.
,
65
Cardiovascular disease in lupus: insights and updates.
]. The IFN-stimulated gene factor 3 (ISGF3) complex was statistically significantly upregulated in CD8+ T-cells from the High ApoB:ApoA1 group. Activation of this signalling pathway, including phosphorylation of signal transducers and activators of transcription (STAT)1 and STAT2 and heterodimerization with IFN regulatory factor (IRF)9 (part of the ISGF3 complex) can lead to pro-inflammatory and atherogenic responses [
66
- Blaszczyk K
- Nowicka H
- Kostyrko K
- Antonczyk A
- Wesoly J
- Bluyssen HAR.
The unique role of STAT2 in constitutive and IFN-induced transcription and antiviral responses.
,
67
- Szelag M
- Piaszyk-Borychowska A
- Plens-Galaska M
- Wesoly J
- Bluyssen HAR.
Targeted inhibition of STATs and IRFs as a potential treatment strategy in cardiovascular disease.
,
68
- Niessner A
- Sato K
- Chaikof EL
- Colmegna I
- Goronzy JJ
- Weyand CM.
Pathogen-sensing plasmacytoid dendritic cells stimulate cytotoxic T-cell function in the atherosclerotic plaque through interferon-alpha.
]. In support of this, an antimalarial drug, artesunate, downregulated IFN induced STAT1 phosphorylation in SLE PBMC’s in vitro, which reduced production of macrophage migration inhibitory factor (MIF), a key regulator of both atherosclerosis and SLE [
69
- Feng X
- Chen W
- Xiao L
- Gu F
- Huang J
- Tsao BP
- et al.
Artesunate inhibits type I interferon-induced production of macrophage migration inhibitory factor in patients with systemic lupus erythematosus.
]. Clinical trials blocking Type-I IFN and JAK/STAT signalling are underway and could help target atherosclerosis as well as autoimmune inflammation [
70
Targeting interferons and their pathways in systemic lupus erythematosus.
,
71
New therapies for systemic lupus erythematosus — past imperfect, future tense.
]. In addition, patients with a high ApoB:ApoA1 ratio had increased longitudinal disease activity over 5 years follow up. Interplay between altered circulating lipids and the pro-inflammatory profile of CD8+ T-cells could partly explain these outcomes, as suggested by increased IFN signalling pathways, further supporting the use of these anti-inflammatory therapies. It is important to note that CD4+ T-cells in patients with a high ApoB:ApoA1 ratio showed increased response to oxidative stress signalling, a process that has been implicated in atherosclerosis through oxidization of LDL and altered inflammatory processes [
72
- Kattoor AJ
- Pothineni NVK
- Palagiri D
- Mehta JL.
Oxidative stress in atherosclerosis.
].
This project has some limitations. Our cohort included mainly patients with low disease activity; therefore, it will be important in future studies to investigate further the lipidomic profile of active and inactive JSLE patients and their utility versus conventional lipid measurements. We are aware of the impact of drugs including hydroxychloroquine, rituximab and cyclophosphamide on lipid profiles [
15
- Cairoli E
- Rebella M
- Danese N
- Garra V
- Borba EF.
Hydroxychloroquine reduces low-density lipoprotein cholesterol levels in systemic lupus erythematosus: a longitudinal evaluation of the lipid-lowering effect.
,
29
- Novikova DS
- Popkova TV
- Lukina GV
- Luchikhina EL
- Karateev DE
- Volkov AV
- et al.
The effects of rituximab on lipids, arterial stiffness, and carotid intima-media thickness in rheumatoid arthritis.
] and patients treated with rituximab and cyclophosphamide within the past year were excluded from the study. There can be challenges related to oral treatment compliance in this patient population, we did not measure blood levels of hydroxychloroquine or steroids to check compliance to treatment dose. None of the JSLE patients included in our study declared that they were smokers; but again we recognise the limitations of self-reported data, especially in this age group. Measurement of endothelial or vascular dysfunction and assessment for presence of atherosclerotic plaque in this patient group was beyond the scope of the study; we used an adult SLE patient group scanned for presence of subclinical atherosclerotic plaque to validate the identified lipid biomarkers and used published literature data to validate DEGs from CD8+ T-cells isolated from human/mouse atherosclerotic plaques. The small sample size used in this study may be masking further clinically important results. It will be important to validate this work in a larger multi-centre study to increase the sample size for metabolomic and transcriptomic analyses, as well as account for genetic, environmental and dietary differences in JSLE, although this cohort was ethnically diverse and we accounted for the majority of conventional CVD risk factors and disease outcome measures in our analysis. JSLE is a rare disease, representing only 15-20% of all SLE patients, thus recruitment of large patient numbers within this age group poses numerous challenges. Future research will address both clinical validation (including endothelial dysfunction studies and measurement of plaque and intimal-media thickness) as well as potential therapeutic interventions.
In conclusion, this study, identified relationships between altered lipid taxonomy, immune cell profiles and gene expression patterns in JSLE patients, which could be associated with increased cardiometabolic risk. There are no guidelines for CVD risk monitoring or management in patients with SLE/JSLE, thus there is an urgent need to find better ways to stratify these patients based on their CVD risk and identify adequate therapeutic approaches to decrease the overall CVD morbidity and mortality associated with SLE. This study proposes high ApoB:ApoA1 ratio as a potential biomarker to stratify JSLE patients for a more personalised approach to lipid modification therapy.
Contributors
Design of research study; ECJ, IPT, CC, YI. Acquiring data; GAR, KEW, MN, AR, HP, CW. Recruiting patients; CC, YI, CW, DAI. Analyzing data; GAR, LC, JP, KEW, ECJ, IPT: Writing the manuscript; GAR, ECJ: Review of the manuscript; CC, IPT, DAI. All authors reviewed and edited the final version.
