Title: Measuring immunocompetence by assessment of torque-teno virus levels in autoimmune diseases following initiation of immunosuppression
Funder: Versus Arthritis

Abstract: Background: Autoimmune disorders have a profound impact on quality of life. Immune system suppressing treatments are used to control disease activity in these disorders. It is desirable to minimise the risk of complications, such as infections, from these treatments. A person’s “immunocompetence” is their ability to maintain a functioning immune system capable of responding to and clearing infections with no or minimal disease activity. There are currently no markers, either disease characteristics or laboratory tests, to predict a “normal immunocompetence” across different autoimmune disorders. A non-pathogenic (unable to cause disease) virus called torque teno virus (TTV) has been used in transplant medicine to predict the risk of organ rejection (if TTV load was low) and infectious complications (if TTV load was high). No such investigations with samples collected at different time points have been conducted in autoimmune disorders so far. Aims and Purposes of this proposal: This study will investigate whether TTV load is a measure of “immunocompetence” in autoimmune disorders. TTV measurements will be performed in two autoimmune diseases; anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) and systemic lupus erythematosus (SLE) with a focus on kidney involvement; lupus nephritis (LN). Experimental plan: The first step of the study is to analyse, over time, the TTV load in patients with AAV treated with two different immunosuppressants - either rituximab or cyclophosphamide/azathioprine – and then confirm our findings in independent, well-defined cohorts from other clinical trials. Investigations will be extended to patients with LN, as they also have an increased risk of disease flares and serious infections leading to morbidity and mortality. This study will therefore investigate the role of TTV load in two autoimmune disorders on two endpoints; a) the predictive value of low TTV load on disease relapse/flare and b) the predictive value of high TTV load on serious infections. Potential patient benefit: If TTV load can predict one of the endpoints of interest, TTV measurements will impact on the care of patients with autoimmune disorders by becoming a part of routine laboratory investigations. This might be further expanded to other autoimmune disorders that are characterised by an increased risk of disease recurrence (flares) and/or serious infections. The measurement of TTV load in autoimmune disorders might reduce the burden of both active disease after remission and infections; both of which are responsible for high morbidity rates and premature mortality of both diseases studied in this project. This study involves input of the charities Vasculitis UK and LUPUS UK, which are important partners to conduct studies like this and translate scientific findings to a broad population living with the respective autoimmune disorders.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION;INFLAMMATORY AND IMMUNE SYSTEM