Immunology

Our Theme focuses on diseases relevant to our local population grouped into (i) antibody-mediated disorders; (ii) thrombo-inflammation; (iii) glomerulonephritis and (iv) renal transplantation. We combine the world-leading immunology and inflammation expertise within the academic Centres for Inflammatory Disease and Haematology with the translational research expertise of our multidisciplinary Clinical Centres. The Theme sits within Imperial College’s Department of Immunology and Inflammation – news updates from the Department can be found here.

• Precision medicine for immune thrombocytopenia and Systemic Lupus Erythematosus to improve diagnostics; treatment pathways; and clinical outcome.
• Identify molecular signatures of disease relapse in Giant Cell Arteritis
• Define the role of endothelial dysfunction in the development of vascular disease in Antiphospholipid Antibody Syndrome
• Utilise diagnostic renal pathology to develop novel biomarkers in glomerulonephritis
• Optimise outcome in renal transplantation by personalised drug treatments derived from the individual risk of rejection and the development of non-invasive diagnostic tests, a patient-defined priority.

The detailed Theme objectives can be found here.

The theme has supported several pilot projects led by our early-stage researchers and all focus on improving the outcome of patients with these conditions. Details of the projects can be found under Pilot Projects tab. These projects include:

• Can T-cell receptor sequencing and gene expression profiling deliver personalised therapy in Immune Thrombocytopenia? Led by Dr Amna Malik, supervised by Dr Nichola Cooper
• Endothelial dysfunction in thrombotic autoimmune disorders Led by Dr Deepa Arachchillage
• Optimizing B cell therapy response in lupus through comprehensive characterization of peripheral blood immune cells. Led by Dr Norzawani Buang and supervised by Dr James Peters and Prof Matthew Pickering
• Spatial Transcriptomic analysis of temporal artery biopsies to identify novel therapeutic targets and biomarkers in Giant Cell Arteritis. Led by Dr Robert Maughan and supervised by Dr James Peters
• Identifying Novel Treatment Targets in Minimal Change Disease. Led by Dr Charli Seneschall and supervised by Profs Megan Griffith and Matthew Pickering
• Clinical Implementation of New Markers of Kidney Disease. Led by Dr Candice Roufosse.
• Spatial Transcriptomics for the Investigation of Antibody-Mediated Injury in Kidney Transplants. Led by Dr Candice Roufosse.

We have also supported the following Fellowship Applications:

• Minimising allosensitisation to red blood cell transfusions in people with a transplant or on the transplant wait-list for Katrina Spensley

We have extensive expertise in Kidney Transplantation led by Drs Michelle Willicombe and Candice Roufosse and our work is internationally recognised for developing biomarkers of kidney rejection risk, with several publications on transcript analysis of biopsy material to improve diagnosis, on the clinical impact of allo-sensitisation following blood transfusion, and on the characterisation and effects of de novo development of antibodies against the transplant. Work is now focussing on translating risk markers and new biomarkers into clinical diagnostic tools via clinical trials and international collaborations (www.icdot.org) (https://banfffoundation.org/). Our remit also includes investigations of radiological features of rejection (flow-MRA), the role of autoimmunity in rejection, and other non-invasive biomarkers of rejection, a key priority for patients. Through collaboration with the Digital Health theme, we are also exploring machine learning applications in digital pathology to improve diagnosis, with a strong focus on patient involvement.

Using Advanced Gene Mapping to Better Understand and Diagnose Kidney Transplant Rejection

What is this project about?

Kidney transplantation is the best treatment for end-stage kidney failure, offering patients significantly better outcomes and quality of life than dialysis. However, the transplanted kidney can be attacked by the recipient’s own immune system — a process called rejection — which can ultimately cause the transplant to fail. Currently, rejection is diagnosed by examining a small piece of kidney tissue under a microscope, but this approach has important limitations: it can only detect changes that are visible, and different pathologists can interpret the same sample differently. This project used a cutting-edge technique called spatial transcriptomics to study kidney transplant biopsies in a completely new way — mapping which genes are switched on or off in specific cells and regions of the kidney tissue, while keeping the structure of the tissue intact. This allows researchers to pinpoint exactly which cells are driving rejection and why, opening the door to more precise diagnosis and targeted treatments.

Why does it matter?

Understanding rejection at the level of individual cells rather than just what can be seen under a microscope could transform how transplant rejection is diagnosed and managed. Knowing what the cause of rejection doctors could one day select treatments tailored to the specific molecular changes happening in each patient’s kidney. This would improve outcomes for transplant recipients, reduce the risk of unnecessary or harmful immunosuppression, and potentially lead to entirely new drugs that target the precise biological processes driving rejection.

What are the outputs of the project?

Sixteen kidney biopsy samples were carefully selected from tissue archives to represent the full spectrum of rejection, quality-checked, and prepared for spatial transcriptomics analysis. During the project, a newer and more powerful version of the spatial transcriptomics technology CosMx became available and the team adapted their approach to take advantage of this more advanced method. Samples have been processed and quality control completed, with analysis now underway in collaboration with a specialist partner. The project is directly linked to a major MRC award in collaboration with Lucy Collinson at the Crick Institute: Nanopathology Platform for Prediction and Early Detection of Transplant Rejection. A collaboration with Richard Mittner at the Crick Institute supports the advanced imaging components of the work.

How were patients and the public involved?

The research has clear and direct relevance to the thousands of kidney transplant recipients in the UK, and the linked MRC project provides a broader platform through which patient perspectives will be incorporated as the work progresses toward clinical application.

Investigating the Role of Blood Vessel Damage in Developing Blood Clots in Autoimmune Disorders

What is this project about?

The lining of our blood vessels, called the endothelium, plays a vital role in keeping blood flowing freely by producing natural anti-clotting substances and keeping vessels relaxed and open. In conditions such as antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE), the immune system produces antibodies that damage this protective lining, making patients highly prone to dangerous blood clots including strokes and clots in the lungs. Despite being treated with blood thinners, 30-40% of patients with APS still experience recurrent clots. This project investigated whether measuring the health of blood vessel lining — both directly using a non-invasive device and indirectly through blood tests — could help identify which patients are at highest risk and whether current treatments are improving blood vessel health.

Why does it matter?

Currently, there are no reliable tests to predict which patients with APS or SLE are most likely to suffer another blood clot, making it very difficult for doctors to decide how intensively to treat individual patients. Blood thinners are the standard treatment but can carry a significant risk of bleeding. Moreover, such treatment does not directly target the blood vessel lining itself. By identifying specific blood markers that reflect the health of the endothelium and correlate with clotting risk, this project could enable doctors to tailor treatment to each patient’s individual risk level: giving more intensive treatment to those who need it and sparing others from unnecessary medication. It could also open the door to entirely new treatments that target the blood vessel lining directly, potentially being more effective and safer than current blood thinners.

What are the outputs of the project?

One hundred patients with APS with or without SLE and 30 healthy controls have been recruited, with 64 patients completing a second visit to assess changes after starting or changing treatment. Key findings show that levels of several protein markers were significantly higher in patients with APS especially those who have had multiple clots compared to those with a single clot and healthy controls. The study demonstrated that current therapies may be improving blood vessel health. Moreover, a potential new therapeutic target was identified. The results were presented at several international meetings including the International Society for Haemostasis annual meeting (Washington DC, 2025), and the 18th International Congress on Antiphospholipid Antibodies (Kyoto, 2025). A £19,439 grant from APS Support UK has been secured to investigate microRNA signatures in APS patients, and an international collaboration with the International Society for Haemostasis and Thrombosis (ISTH) and APS ACTION is using samples and data from this project to study differences in clotting patterns between patients.

How were patients and the public involved?

This project was conceived directly from feedback given by patients attending Dr Arachchillage’s dedicated APS clinic, who expressed deep concern about the fear of suffering another blood clot — particularly a stroke — and a desire for reassurance that their treatments were working. These patient priorities shaped the entire design of the study, including the decision to use the EndoPAT device to give patients a direct, non-invasive assessment of their blood vessel health at two time points — providing tangible reassurance and reducing anxiety. Five patients from the APS clinic reviewed the study information sheet and consent forms before recruitment began, ensuring the study was clearly understood and acceptable to those it was designed to help. The study was also presented at the National Patient and Public Engagement Day in collaboration with Thrombosis UK in January 2025, raising awareness and boosting patient participation. Regular feedback from patients continues to inform how the study is conducted, and findings were communicated directly to patient representatives at the International Congress on Antiphospholipid Antibodies in Kyoto.

Studying the Immune System to Predict Recovery in Patients with Immune Thrombocytopenia

What is this project about?

Immune thrombocytopenia (ITP) is a condition where the immune system mistakenly attacks platelets — the tiny cells in blood that help it clot and stop bleeding. People with ITP have very low platelet counts, leaving them vulnerable to bruising and bleeding. While some patients recover quickly on their own, others develop a long-term, chronic form of the disease that requires ongoing treatment. Currently, there is no reliable way for doctors to predict at the time of diagnosis which patients will recover quickly, and which will not leading to uncertainty, anxiety, and in some cases, patients receiving either too much or too little treatment. This project investigated whether analysing the unique “fingerprints” of immune cells called T cells could help predict which patients are likely to go into remission and which are likely to develop chronic disease.

Why does it matter?

The inability to predict disease course in ITP creates real difficulties for patients and their families, particularly children and parents who face the distressing uncertainty of not knowing what lies ahead. Better prediction tools would allow doctors to tailor treatment more precisely: giving more targeted therapy earlier to those who need it, while sparing others from unnecessary side effects. In the longer term, understanding which immune cells are driving the disease could also reveal new targets for treatments that are more effective and better tolerated than current options.

What are the outputs of the project?

The project analysed T cell receptor (TCR) sequences from two patient cohorts at Imperial College (London) and Stanford University (San Francisco), including 52 children with ITP and 18 healthy controls. TRC sequence analysis allows the team to track how many times each specific T cell produce a copy of itself. The study revealed that patients in which samples T cells produce unusually large numbers of identical copies, or speaking scientifically with expanded T cell clones, take on average twice as long to recover and have variable disease courses when compared to the patient without expanded clones. This feature is statistically independent of platelet count, meaning T cell expansion can provide genuinely new prognostic information beyond standard blood tests. The team also identified virus-specific T cell clones — particularly those associated with common viruses such as CMV and EBV — suggesting that prior viral infections may influence how ITP develops. Computational analysis further identified specific platelet proteins that the expanded T cell clones may be targeting, including proteins essential for platelet adhesion and function, pointing toward potential new therapeutic targets. TCR sequencing was carried out in collaboration with the BRC Genomics Facility, and the team is now expanding the cohort to validate findings in a larger group of newly diagnosed patients.

How were patients and the public involved?

BRC Community Partners were involved from the very outset, with the study design informed by patient surveys and research update days that identified prediction of treatment response as an unmet need of the highest priority. Community Partners reviewed the pilot application, provided feedback on the study objectives, and their recommendations ensured the project remained focused on outcomes that matter most to patients. Patient engagement days and interviews with patient groups including parents of children with ITP highlighted the significant burden of uncertainty at diagnosis, the challenges of treatment side effects, and the importance of reducing unnecessary treatment. This input directly shaped the team’s focus on developing clinically meaningful prognostic tools and has ensured the project remains patient-centred throughout.

Lupus Patients with More Immune System Alarm Signals Are More Likely to Experience Worse Symptoms

What is this project about?

Lupus (systemic lupus erythematosus, or SLE) is a serious autoimmune condition in which the immune system attacks the body’s own tissues, causing inflammation in organs including the kidneys, joints, skin, and brain. Managing lupus is challenging because the disease varies enormously between patients: some experience mild symptoms while others suffer severe, life-threatening flares. This project built a detailed database of clinical, immunological, and molecular information from over 350 lupus patients, and used it to investigate whether measuring specific immune system activation signatures – levels of interferons – in routine blood tests could help predict which patients are likely to have more severe disease and need more intensive treatment.

Why does it matter?

Currently, doctors have limited tools to predict which lupus patients will deteriorate and need escalation to more powerful treatments such as biologics. Identifying patients at higher risk earlier — before serious organ damage occurs — could allow doctors to intervene sooner and more precisely, improving outcomes and reducing the long-term burden of the disease. Interferons are proteins that act as alarm signals, ramping up the immune system in response to threats.

What are the outputs of the project?

A comprehensive database of over 350 lupus patients has been established, incorporating clinical data, immunological parameters, whole genome sequencing, and plasma proteomic and metabolomic profiles. High-sensitivity measurement of circulating interferon proteins has been performed and validated. This project found that patients with higher interferon levels in their blood were more likely to have worse symptoms and a higher disease burden in the future — suggesting that measuring these proteins at routine clinic visits could be a practical and clinically valuable tool for guiding treatment decisions. A Polygenic Risk Score for lupus is being developed and validated in collaboration with Prof Timothy Vyse at King’s College London, and proteomics work is being conducted with Prof Eric Morand at Monash University. Genomic sequencing and single-cell transcriptomic analysis is being carried out with Dr Emma Davenport at the Wellcome Sanger Institute. A major Lupus Research Alliance Global Team Science Award of USD 2,913,103 has been secured — with £250,000 coming to Imperial — to study molecular profiles and genetic origins of ancestral phenotypic diversity in lupus across multiple international centres.

How were patients and the public involved?

The project was reviewed by Community Partners from the Immunology Theme, whose feedback was incorporated into the research design and execution. Research progress was presented by Ms Charlotte Bottomley at the Immunology Theme Executive Meeting, attended by both research staff and community partners, ensuring ongoing transparency and accountability to those affected by lupus. Patient and public perspectives have helped ensure the project remains focused on outcomes that are clinically meaningful and relevant to the lived experience of people with lupus.

Molecular Mapping of Giant Cell Arteritis to Identify New Treatments and Diagnostic Tests

What is this project about?

Giant cell arteritis (GCA) is a serious condition in which the immune system mistakenly attacks the walls of large blood vessels particularly those supplying the head and eyes. It is the most common form of vasculitis in older adults, affecting around 20 in every 100,000 people over the age of 50, and its prevalence is expected to rise as the population ages. If not diagnosed and treated quickly, GCA can cause permanent blindness and other severe complications. Currently, diagnosis is slow and often requires multiple specialist investigations, including a surgical biopsy of the temporal artery. Treatment relies heavily on high-dose steroids, which carry serious side effects including diabetes, osteoporosis, and increased infection risk. This project used a powerful technique called spatial transcriptomics to create detailed molecular maps of artery tissue from GCA patients, identifying the specific cells and proteins driving the disease — with the aim of developing better blood tests for diagnosis and new, more targeted treatments.

Why does it matter?

The lack of reliable blood tests to diagnose GCA quickly or detect relapses during steroid reduction is a major unmet clinical need. Patients frequently experience long delays before diagnosis, and many suffer relapses that are difficult to detect until significant damage has already occurred. Even mild symptoms cause significant anxiety because patients cannot be sure whether they represent a true relapse. By identifying the molecular signatures of active disease in both blood and tissue, this project is laying the groundwork for blood tests that could diagnose GCA faster, replace the need for surgical biopsy, and detect relapses earlier — transforming the patient experience and reducing the risk of serious complications.

What are the outputs of the project?

Spatial transcriptomics experiments using the Xenium platform have been completed on temporal artery biopsies from GCA patients, mapping the activity of 5,095 genes to their precise location within diseased artery tissue. A key focus has been on multi-nucleated giant cells (MGCs) — a distinctive immune cell type believed to drive arterial damage in GCA. 59 genes were found to act abnormally in these cells, pointing toward promising new therapeutic targets. By integrating this tissue-level data with previously published data on protein content of the plasma, 30 proteins were identified that are dysregulated at both the tissue and blood level in strengthening their candidacy as diagnostic biomarkers. A key publication — “Proteomic Profiling of the Large-Vessel Vasculitis Spectrum Identifying Shared Signatures of Immune Activation and Stromal Remodelling” — has been published in Arthritis & Rheumatology (2025) and featured in press releases on both the NIHR Imperial BRC and Imperial College London websites. Collaborations have been established with Prof Ann Morgan (Leeds), Prof Raashid Luqmani (Oxford), Dr Maria Sandovici (University of Groningen), Dr Jason Tarkin (Cambridge), Dr Gary Reynolds (Harvard), Vasculitis UK, and the Imperial Vasculitis Centre, supporting biomarker validation, novel radiotracer development, and single-cell analyses in GCA arterial tissue.

How were patients and the public involved?

Patient involvement has been central and meaningful throughout the project. The research was reviewed by the BRC Community Partners group — composed of patients with immune-mediated diseases at Imperial College Healthcare NHS Trust — whose feedback was highly supportive and directly shaped the research priorities. Patients shared detailed accounts of their diagnostic journeys, frequently describing long delays, repeated tests, and significant anxiety both at diagnosis and during treatment. Their strong endorsement of the goal to develop better blood-based diagnostic tests directly influenced the team’s decision to prioritise this as a key research outcome, and their questions about whether blood tests could eventually replace the temporal artery biopsy have been incorporated into future research plans. Patients also highlighted the burden of relapse uncertainty during steroid tapering, reinforcing the importance of developing reliable monitoring tools. Engagement took place through formal events, dedicated feedback sessions via the Imperial Vasculitis Centre, and individual consultations, with patients and community partners committed to reviewing future manuscripts and lay summaries before publication.

We have recruited Community Partners with lived experience of the conditions within our Theme and held our first meeting on the 28^th of June 2023. Our partners will help co-produce our research and provide expertise in the patient perspective on all our translational research initiatives. We hold specific events on PPIE and a recent example is “Digital Pathology and AI: Learning what matters to patients who have undergone a kidney transplant”

Our researchers are based in the Department of Immunology and Inflammation and the department has an active EDI committee

The Department of Immunology and Inflammation holds an Athena Swan Silver Award and our mission statement is to create a diverse, inclusive and supportive academic community committed to promoting scientific excellence and nurturing the next generation of researchers. The principles we adhere to are Transparency and consistency, Equality and diversity, Professional behaviour and Scientific integrity

• The role of CD8+ T-cell clones in immune thrombocytopenia
• Steroid Sparing Maintenance Immunosuppression in Highly Sensitised Patients Receiving Alemtuzumab Induction
• Application of the Banff Human Organ Transplant Panel to kidney transplant biopsies with features suspicious for antibody-mediated rejection

In accordance with the Imperial BRC’s PPIEP Strategy , our theme has recruited a group of Community Partners to act as critical friends to our theme and share their valuable lived experience with our researchers and health professionals to help improve the relevance and quality of our research for the benefit of our North West London population.

‘I am a director at a human rights charity, a former school governor, and current ITP patient at Hammersmith Hospital.’

Benjamin Ward