Relation of Antibodies Against Oxidized Low Density Lipoproteins to Disease Activity and Cardiovascular Affection in Systemic Lupus.

NCT ID: NCT05479071

Last Updated: 2022-07-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-09-01

Study Completion Date

2023-10-01

Brief Summary

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The aim of this study is to correlate the autoantibody against oxidized LDL with disease activity and cardiovascular affection in patients with SLE.

Detailed Description

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Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease affecting mainly women of fertile age. It is characterized by hyperactivity of B-cells and by overproduction of autoantibodies without organ specificity, many of which contribute to the formation of immunocomplexes. Their deposition in tissues and blood vessels results in inflammatory organ impairment (Khairy et al., 2017). As for the laboratory findings in SLE, production of autoantibodies without organ specificity aimed at nuclear, cytoplasmic, and surface antigens of the patient's body is typical. The most common SLE manifestations include involvement of skin, joints, cardiovascular system, lungs, renal glomeruli, central nervous system or hematopoiesis.

SLE can result in failure of the involved organs, severe forms of SLE thus bein gassociated with significant mortality (Pashnina et al., 2021).

Cardiovascular involvement is associated with increased morbidity and mortality of SLE patients. The most common SLE-related cardiovascular events are myocardial infarctions (MIs), cerebrovascular events, thromboembolic events (TEs), heart failure, and sudden death.

Cardiovascular events are proportionally higher in SLE compared to general populations of comparable age and sex (Ramirez et al., 2020). The pathogenic mechanisms of different cardiac diseases in SLE are still incompletely understood. Traditional risk factors for Cardiovascular affection, such as older age, high blood pressure (BP), high cholesterol and triglycerides, smoking, obesity, diabetes mellitus, and - last but not least - SLE therapy all play a critical role. These factors alone cannot adequately explain the increased incidence of cardiovascular disease commonly reported in patients with SLE. Metabolic syndrome was considered a remarkable risk factor for the development of subclinical atherosclerosis and increased carotid intima-media thickness The non-traditional biomarkers included both leptin and homocysteine, where leptin acts on the immune system as aproinflammatory cytokine. It promotes the proliferation and activation of T lymphocytes and induces production of Th1 cytokines. Homocysteinelevels have been identified as a predictor of atherosclerosis in patients with SLE, in whom high levels may be predictive levels of coronary calcification, platelet progression and increased IMT (Khairy et al., 2017).

Specific antibodies cause oxidation of low density lipoprotein (LDL) particles, thus accentuating their atherogenic effect, or exert a negative influence on the character of physiologically protective High density lipoprotein (HDL) particles. Endothelial dysfunction within the vascular system ensues, increasing its vulnerability, affinity to lipoproteins and activity of enzymes accelerating the development of atherosclerosis (Li et al., 2020).

LDLs are transported into artery walls, where they become trapped and bound in the extracellular matrix of the subendothelial space. These trapped LDLs are then seeded with reactive oxygen species produced by nearby artery wall cells, resulting in the formation of proinflammatory Oxidized LDL (OxLDL). oxLDL plays an important role in atherogenesisand may contribute to the immune activation and inflammation present in the atherosclerotic lesions, because it has chemotactic, immune-stimulatory, and toxic properties and is taken up by macrophages and other cells in the atherosclerotic plaque, which develop into foam cells. Epitopes characteristic of oxidized LDL can be found in atherosclerotic lesions by immunocytochemical techniques and atherosclerotic lesions contain immunoglobulins that recognize oxLDL (Ammar et al., 2021).

Conditions

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SLE

Study Design

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Observational Model Type

COHORT

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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SLE patients WITH cardiovascular disease

Relation of antibodies against LDL to disease activity in pt with cardiovascular disease

Blood test

Intervention Type DIAGNOSTIC_TEST

Screening of antibodies against LDL

SLE Patients without cardiovascular disease

Relation of antibodies against LDL to disease activity in pt without cardiovascular disease

Blood test

Intervention Type DIAGNOSTIC_TEST

Screening of antibodies against LDL

Interventions

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Blood test

Screening of antibodies against LDL

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

\- 1. Patients aged ≥ 18 years. 2. Patients fulfilling the American College of Rheumatology (ACE) criteria for SLE (Aringer et al., 2019).

3\. Patients diagnosed with SLE and without cardiovascular disease (CVD) impairment before the diagnosis of SLE was established.

Exclusion Criteria

1. Patients aged less than18 years.
2. Patients not fulfilling the American College of Rheumatology (ACE) criteria for SLE (Aringer et al., 2019).
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Assiut University

OTHER

Sponsor Role lead

Responsible Party

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HADDEEL AHMED MOHMED SAYED AHMED

Dr

Responsibility Role PRINCIPAL_INVESTIGATOR

Central Contacts

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Haddeel Sayed ahmed, Dr

Role: CONTACT

0020109427161

Osama Ibraheem, Pro

Role: CONTACT

00201006372498

References

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Wu R, Svenungsson E, Gunnarsson I, Haegerstrand-Gillis C, Andersson B, Lundberg I, Elinder LS, Frostegard J. Antibodies to adult human endothelial cells cross-react with oxidized low-density lipoprotein and beta 2-glycoprotein I (beta 2-GPI) in systemic lupus erythematosus. Clin Exp Immunol. 1999 Mar;115(3):561-6. doi: 10.1046/j.1365-2249.1999.00830.x.

Reference Type BACKGROUND
PMID: 10193434 (View on PubMed)

Wu R, Svenungsson E, Gunnarsson I, Andersson B, Lundberg I, Schafer Elinder L, Frostegard J. Antibodies against lysophosphatidylcholine and oxidized LDL in patients with SLE. Lupus. 1999;8(2):142-50. doi: 10.1191/096120399678847434.

Reference Type RESULT
PMID: 10192509 (View on PubMed)

Kurien BT, Scofield RH. Autoimmunity and oxidatively modified autoantigens. Autoimmun Rev. 2008 Jul;7(7):567-73. doi: 10.1016/j.autrev.2008.04.019. Epub 2008 May 27.

Reference Type RESULT
PMID: 18625446 (View on PubMed)

Tektonidou MG. Cardiovascular disease risk in antiphospholipid syndrome: Thrombo-inflammation and atherothrombosis. J Autoimmun. 2022 Apr;128:102813. doi: 10.1016/j.jaut.2022.102813. Epub 2022 Mar 2.

Reference Type RESULT
PMID: 35247655 (View on PubMed)

Tso TK, Huang WN. Elevation of fasting insulin and its association with cardiovascular disease risk in women with systemic lupus erythematosus. Rheumatol Int. 2009 May;29(7):735-42. doi: 10.1007/s00296-008-0781-7. Epub 2008 Nov 27.

Reference Type RESULT
PMID: 19037607 (View on PubMed)

Other Identifiers

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SLE

Identifier Type: -

Identifier Source: org_study_id

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