The function of genetic variants in immune cells (IRAS 169847)

The study explores how a person's genes and the mix of bacteria in their gut affect the body’s immune system. We will compare healthy people and people with immune diseases to understand differences in immune responses. Our research may help develop new treatments that can better control harmful immune reactions and improve therapies for immune-related diseases.

Our study looks at how the body’s immune system works. Immune cells in the blood help protect us from illness and infection, but they must be carefully controlled so that they do not attack the body by mistake. When this happens, it can cause serious autoimmune diseases.

We want to discover:

• which genes control how people’s immune cells behave
• how gut bacteria affect how the people’s immune systems function.

To do this, we will study people who have immune-related diseases and those who do not to understand the differences between them.

We will also explore whether changing certain genes could help reduce harmful immune responses. This research could help the global research community develop better treatments and new therapies for diseases linked to the immune system.

Rationale

This study aims to understand how genetic differences influence the way the immune system works. The immune system must respond quickly to infection while also remaining controlled to avoid harmful inflammation and autoimmune diseases such as lupus. We will study blood samples from healthy volunteers and people with immune-related diseases to investigate how genes affect immune cell behaviour.

The study will examine:

• which genes are active in immune cells,
• how genetic changes influence immune responses,
• how immune cells react to signals from bacteria or other triggers.

We will also use laboratory techniques to alter specific genes to better understand their role in immune function.

By identifying the genetic pathways involved in immune diseases, we hope to improve understanding of why these conditions develop and support the development of new and more targeted treatments in the future.

Aims

This study aims to:

• Understand how genetic differences influence the immune system and contribute to immune-related diseases.
• Study immune cells from healthy volunteers and people with immune diseases.
• Identify genes that control immune responses and investigate how these genes are regulated.
• Examine how immune cells respond to different triggers, including bacterial products.
• Determine how altering specific genes affects immune cell behaviour.

Primary Outcome

Our outcome measures relate to uncovering the molecular mechanisms by which underlying changes in the sequence of DNA (genetic variants) direct the development of immune diseases. Identifying these mechanisms may, in the future, facilitate the development of targeted therapies.

Outcome measures may include:

• Identification of changes in the sequence of DNA (gene variants)
• DNA and RNA sequences
• Profiles of gene activity in different types of immune cells
• Numbers and proportions of different immune cell types
• Parameters related to the immune response potential of a cell, including the potential for proliferation, differentiation into other cell types, migration, activation, as well as the ability to regulate the activity of other cell types
• Abundance of specific cellular proteins (cellular markers) in different immune cell types

Key Secondary outcome(s)

N/a

Study Type

Observational

Participant and Sample Information

Populations involved:

Healthy volunteers and people with immune-related diseases.

Countries of recruitment:

UK

Approximate participant or sample numbers (if applicable):

600

Key inclusion criteria:

• NHS Blood and Transplant blood donors who have consented for their blood samples to be used in research.
• Clinical Trials Laboratory Services blood donors who have consented for their blood samples to be used in research.

Key exclusion criteria:

• Blood donors who have not consented for their blood samples to be used in research.

Recruitment status:

Non-recruiting: Pre-collected samples only.

Governance and Ethical Approval

Governance and oversight:

Study Sponsor: Wellcome Sanger Institute

All work conducted at the Wellcome Sanger Institute is reviewed and overseen by institutional Research Governance processes, ensuring compliance with ethical, legal, and regulatory requirements.

Ethical approval:

This study has been reviewed by the North West – Preston NHS Research Ethics Committee. The study received REC approval on 23 March 2015.

IRAS 169847

REC reference: 15/NW/0282

Data and Sample Use

Data sharing:

Anonymised DNA sequence data are stored in the European Genome-Phenome Archive (EGA) and made available to bonafide researchers via managed access, subject to data access agreements. Anonymised samples and cultured cells may also be shared with other legitimate research organisations under appropriate legal agreements.

IPD sharing statement

Deidentified individual participant-level data (IPD) will not be shared as part of this study.

Completion date

Ongoing

Further Information

For enquiries about the scientific aims of this study or potential collaboration, please contact the relevant scientific programme https://www.sanger.ac.uk/programme/human-genetics/

For enquiries relating to research governance, ethics, or regulatory oversight, please contact the Research Governance team at researchgovernance@sanger.ac.uk.