The Role of Lipids in Immune Cell Function in SLE Patients

Understanding the Role Played by Serum and Membrane Lipids in Immune Cell Function in Patients With Systemic Lupus Erythematosus (SLE) and Healthy Donors

The overall aim of this project is to investigate the different types of immune cells found in the blood of patients with Systemic Lupus Erythematosus (SLE) and healthy donors. We know that the amount of fat on the surface of immune cells is an important factor controlling their behaviour. Immune cells from SLE patients are defective and this is associated with changes in the levels of fat on these cells. This project will investigate the level of fat in the blood and on immune cells from patients with SLE and age matched healthy controls, and measure how changes in the amount of fat can affect the way immune cells behave.

Study Overview

• Status: Unknown
• Conditions: Lupus Erythematosus, Systemic
• Intervention / Treatment: Other: Blood sampling to include Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA)

Detailed Description

Accelerated atherosclerosis is a serious complication of autoimmunity including patients with both adult and juvenile onset systemic lupus erythematosus (SLE). This suggests that defects in fat levels could contribute to disease pathogenesis. The immune system in patients with SLE does not work normally. In adult patients with SLE we know that many of the immune cells involved in protecting the body from infections or cancer are over-active and actually cause disease. In young people the immune system is still developing and very little is known about what goes wrong in patients that develop juvenile-onset SLE, whether this is the same as adult disease and whether the same treatments are relevant for this group of patients. This project aims to find out whether immune cells from SLE patients with adult-onset disease have the same defects as adult patients with juvenile-onset SLE. We know that an important factor that controls immune cell behaviour is the amount of fat that they have on their surface. We also know that a change in fat on immune cells from adult patients with SLE makes them defective. This project will investigate the level of fat in the blood and in immune cells from adult patients with juvenile-onset SLE and age matched healthy controls, and measure how changes in the amount of fat can affect the way immune cells behave. We will investigate how drugs that control fat levels can help to normalize the behaviour of immune cells from SLE patients.

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

• Study Contact: Name: Liz Jury, Prof; Phone Number: 02031082161; Email: e.jury@ucl.ac.uk
• Study Contact Backup: Name: George Robinson, Dr; Phone Number: 02031082167; Email: george.robinson.15@ucl.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, NW1 2BU
    • Recruiting
    • University College London Hospitals NHS Foundation Trust
    • Contact: George Robinson, Dr; Phone Number: 02031082167; Email: george.robinson.15@ucl.ac.uk
    • Contact: Amanda Ledlie; Phone Number: 02031082167; Email: a.ledlie@ucl.ac.uk
    • Principal Investigator: David Isenberg, Prof

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients will be approached by the consultant rheumatologist when the patient is attending their normal outpatient clinic appointment.

Healthy donors will be approached in a similar way using information flyers, invitation letters and participant information sheets by a member of the research team.

Healthy volunteers from UCL staff will be made aware of the study and also asked to participate.

Description

Inclusion Criteria:

• Diagnosis of SLE according to American College of Rheumatology revised criteria
• Having given written informed consent prior to undertaking any study-related procedures.
• Male and female patients between the ages of 18 and 80 years.

Patients who have met all the above inclusion criteria listed and healthy donors will be screened for the following exclusion criteria:

Exclusion Criteria:

• Under any administrative or legal supervision.
• Conditions/situations such as:
• A concomitant autoimmune disease
• Impossibility to meet specific protocol requirements (e.g. blood sampling).
• Patient is the Investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol.
• Uncooperative or any condition that could make the patient potentially non-compliant to the study procedures.
• Pregnant or breast-feeding women, currently or in the last three months prior to inclusion.
• Patients who have been vaccinated in the last three months prior to inclusion.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Juvenile onset Systemic Lupus Erythematosus (SLE) patients; All patients who meet the American College of Rheumatology revised criteria for SLE who were diagnosed with SLE between the ages of 11 and 21.	Other: Blood sampling to include Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA); Blood sampling to measure immune cell phenotypes and examine DNA/RNA and identify serum biomarkers.; Food Frequency Questionnaires (FFQs) and/or diet recall questionnaires to assess dietary intake.; Cardiovascular Ultrasound Scans (USS) to measure how well blood is carried around the body.; Other Names: Food Frequency Questionnaires (FFQs) and/or 24 hour diet recall questionnaires; Ultrasound Scan (USS); GTN (glyceryl trinitrate) administration
Adult onset Systemic Lupus Erythematosus (SLE) patients; All patients who meet the American College of Rheumatology revised criteria for SLE who were diagnosed with SLE between the ages of 24 and 80	Other: Blood sampling to include Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA); Blood sampling to measure immune cell phenotypes and examine DNA/RNA and identify serum biomarkers.; Food Frequency Questionnaires (FFQs) and/or diet recall questionnaires to assess dietary intake.; Cardiovascular Ultrasound Scans (USS) to measure how well blood is carried around the body.; Other Names: Food Frequency Questionnaires (FFQs) and/or 24 hour diet recall questionnaires; Ultrasound Scan (USS); GTN (glyceryl trinitrate) administration
Matching healthy volunteers; Healthy volunteers, matched by age and gender, will be used as a control group	Other: Blood sampling to include Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA); Blood sampling to measure immune cell phenotypes and examine DNA/RNA and identify serum biomarkers.; Food Frequency Questionnaires (FFQs) and/or diet recall questionnaires to assess dietary intake.; Cardiovascular Ultrasound Scans (USS) to measure how well blood is carried around the body.; Other Names: Food Frequency Questionnaires (FFQs) and/or 24 hour diet recall questionnaires; Ultrasound Scan (USS); GTN (glyceryl trinitrate) administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Collection of blood samples	Blood sampling to measure immune cell phenotypes and examine DNA/RNA and identify serum biomarkers.	4 hours from point of sample collection
Completion of FFQ's and/or diet recall questionnaires	FFQ's and/or diet recall questionnaires to assess dietary intake	Same day as recruited to study.
Cardiovascular Ultrasound scans (USS)	USS of Intima Media Thickness (IMT), Flow Mediated Dilatation (FMD), Pulse Wave Velocity (PWV) and Laser Doppler Flowmetry measurement. As part of the procedure, sub lingual administration of GTN spray will be administered to measure FMD.	Within 2 months from recruitment.

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: University College London Hospitals
• Investigators: Principal Investigator: David Isenberg, Prof, UCL & University College London Hospitals NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2016
• Primary Completion (Anticipated): August 31, 2020
• Study Completion (Anticipated): August 31, 2020

Study Registration Dates

• First Submitted: April 22, 2020
• First Submitted That Met QC Criteria: April 22, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Actual): April 24, 2020
• Last Update Submitted That Met QC Criteria: April 22, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Vasodilator Agents; Nitroglycerin
• Other Study ID Numbers: 15/0743

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: All participants are required to indicate in written consent if they agree to the use of any left over samples and associated data for future research use.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No