Harnessing technological advances to elucidate the immunological basis of podoconiosis, a neglected HLA-associated cause of tropical lymphoedema
Lead Research Organisation:
University of Sussex
Abstract
Podoconiosis is a disabling neglected tropical disease of the skin that causes painful swelling of the legs in over 4 million people worldwide. It occurs in genetically susceptible people who have prolonged barefoot contact with volcanic clay soil. The lack of affordable footwear to prevent soil contact limits its geographical distribution to low-income countries mainly in Africa where it is an important yet ignored public health problem. Stigma, reduced mobility and painful ‘flare-ups’ of the legs impede activities like farming, exacerbating poverty in already impoverished communities. Diagnosis is based on the presence of swelling and characteristic skin changes. The lack of a diagnostic test prevents early case detection, thus underestimating disease burden and hampering control strategies for what, with sufficient research investment, could be the first non-communicable disease to be eliminated globally.
This project builds on two decades of pioneering research that has advanced knowledge of the cause, epidemiology, treatment and psycho-socioeconomic consequences of podoconiosis. Highlights include the discovery of the genetic basis of podoconiosis, linking it to class II HLA genes which are well-known for their role orchestrating healthy immune responses to protect against infections, but can also provoke ‘self-attack’ when out of control. This leads to damaging over-activity of the immune system which we have documented in our studies on podoconiosis in Ethiopia, which has the highest burden of podoconiosis worldwide.
During this period we have fostered a sustained, equitable partnership between Brighton and Sussex Medical School (University of Sussex) and the Armauer Hansen Research Institute in Addis Ababa. Collaboration with Ethiopian universities, including Arba Minch University, has been instrumental in advancing impactful research and interventions aimed at addressing this neglected disease.
The next steps for podoconiosis research are challenging. The soil trigger remains unidentified and the drivers of the uncontrolled immune responses we have reported are unclear.
This project aims to transform understanding of the disease processes in podoconiosis by:
Using advanced single cell 'omics' technology to identify and compare the different cells present in skin and blood from people with podoconiosis and healthy individuals who are exposed to soil without developing disease.
Undertaking functional studies on immune cells identified in aim 1 to understand how the immune system ‘goes wrong’ in podoconiosis, particularly focusing on cells that regulate immunity.
Studying people with early and more advanced disease to identify markers of disease progression.
Using the findings from aims 1-3 to establish a ‘signature’ that could ultimately be developed into a simple blood test that detects inflammation even before classic symptoms develop, enabling prevention and early intervention.
To achieve our vision in a timely way, we have partnered with Professor Haniffa, a renowned expert in skin research based at the world-leading Wellcome Sanger Institute. Her team of highly qualified scientists, equipped with state-of-the-art technologies, will apply advanced methods to study podoconiosis while training Ethiopian scientists.
The main beneficiaries of this research will be podoconiosis patients, their families and communities, and policy makers in countries where podoconiosis occurs. Our work supports the World Health Organization’s mission to control and eliminate neglected tropical diseases by 2030. Researchers investigating other inflammatory, HLA-associated diseases will benefit from the knowledge our research generates. We will build skills and knowledge in the Ethiopian research team. Finally, the project will generate novel genetic data on African populations, which are currently under-represented in global datasets.
This project builds on two decades of pioneering research that has advanced knowledge of the cause, epidemiology, treatment and psycho-socioeconomic consequences of podoconiosis. Highlights include the discovery of the genetic basis of podoconiosis, linking it to class II HLA genes which are well-known for their role orchestrating healthy immune responses to protect against infections, but can also provoke ‘self-attack’ when out of control. This leads to damaging over-activity of the immune system which we have documented in our studies on podoconiosis in Ethiopia, which has the highest burden of podoconiosis worldwide.
During this period we have fostered a sustained, equitable partnership between Brighton and Sussex Medical School (University of Sussex) and the Armauer Hansen Research Institute in Addis Ababa. Collaboration with Ethiopian universities, including Arba Minch University, has been instrumental in advancing impactful research and interventions aimed at addressing this neglected disease.
The next steps for podoconiosis research are challenging. The soil trigger remains unidentified and the drivers of the uncontrolled immune responses we have reported are unclear.
This project aims to transform understanding of the disease processes in podoconiosis by:
Using advanced single cell 'omics' technology to identify and compare the different cells present in skin and blood from people with podoconiosis and healthy individuals who are exposed to soil without developing disease.
Undertaking functional studies on immune cells identified in aim 1 to understand how the immune system ‘goes wrong’ in podoconiosis, particularly focusing on cells that regulate immunity.
Studying people with early and more advanced disease to identify markers of disease progression.
Using the findings from aims 1-3 to establish a ‘signature’ that could ultimately be developed into a simple blood test that detects inflammation even before classic symptoms develop, enabling prevention and early intervention.
To achieve our vision in a timely way, we have partnered with Professor Haniffa, a renowned expert in skin research based at the world-leading Wellcome Sanger Institute. Her team of highly qualified scientists, equipped with state-of-the-art technologies, will apply advanced methods to study podoconiosis while training Ethiopian scientists.
The main beneficiaries of this research will be podoconiosis patients, their families and communities, and policy makers in countries where podoconiosis occurs. Our work supports the World Health Organization’s mission to control and eliminate neglected tropical diseases by 2030. Researchers investigating other inflammatory, HLA-associated diseases will benefit from the knowledge our research generates. We will build skills and knowledge in the Ethiopian research team. Finally, the project will generate novel genetic data on African populations, which are currently under-represented in global datasets.