Imperial Post-Doctoral, Post-CCT Research Fellowship (IPPRF)

The Role of Factor H Related Protein 5 in Glomerular Complement Activation and Injury in IgA Nephropathy

The role of complement proteins in kidney disease cause by IgA Nephropathy

IgA nephropathy (IgAN) is a kidney disease diagnosed after laboratory tests of a sample of kidney tissue (a biopsy). The severity of IgAN varies markedly between individuals; some have few health problems but others will rapidly develop kidney failure. Kidney failure markedly reduces life expectancy. Kidney failure treatments, including kidney transplantation or artificial kidney function replacement (dialysis), are complex, expensive, inconvenient and unpleasant. We do not have treatments that reliably and effectively prevent progression of IgAN to renal failure. We also do not understand the range of disease severities observed in different individuals with a diagnosis of IgAN. It is important for us to understand how to identify which IgAN patients to treat and how to treat them.
Our immune system is a complex network of cells and proteins that defends us from germs and keeps us healthy. The complement system is a pathway of proteins essential to our immune system. Complement pathway activity targets and damages cells. When complement inappropriately targets heathy tissue, it can cause tissue injury and disease. There is growing evidence that complement pathway activity contributes to the severity of IgAN. However, we don’t understand exactly how this occurs, and which complement proteins actually drive disease. I recently identified new links between a complement protein called FHR5 and the risk of developing IgAN, and cases of particularly severe disease. I am now trying to deduce how and why this occurs. This could lead to the development of new tests that improve the accuracy and thoroughness of IgAN diagnosis, and new targets for medicine to be developed against in the future.

Biography

I am an early career research and clinical academic nephrologist at Imperial College London. My research investigates the role of complement activity in IgAN and C3 glomerulopathy (C3G). I am motivated by the need to improve the clinical diagnosis, stratification and treatments of patients with complement dependent kidney diseases, many of whom are young, have no disease-targeted treatments available and suffer the personal and societal impact of ESRD. In particular, I am interested in the contribution of complement deregulation to disease severity and transplant recurrence and am currently investigating the the role of factor H related protein 5 (FHR5) in IgAN and C3G progression. I aim to improve the understanding of IgAN and C3G pathogenesis, develop complement-based diagnostic techniques, identify novel therapeutic targets, and become an international leader of complement research in glomerular disease. With Professor Terry Cook, Dr Medjeral-Thomas leads the Complement Research Group of the International IgA Nephropathy Network. With the supervision of Professor Matthew Pickering and Professor Terry Cook at Imperial College London, I have produced a number of relevant insights into C3G pathogenesis and the role of complement activity in IgAN. I identified novel FHR5 mutations in familiar C3G, features associated with disease severity in a cohort of C3G patients, and a number of associations between circulating levels and glomerular deposition of complement proteins, including wild-type FHR5, and the severity of IgAN and C3G.