I am an Arthritis Research UK clinical research fellow at UCL. The focus of my work is the immunology of anti-TNF agents in rheumatoid arthritis (RA) and their effect on the human immune response to TB. I am working with Dr Maddy Noursadeghi and Professor Mike Ehrenstein.
I am a rheumatology specialist registrar in London, and have taken time out of my training programme to undertake a PhD. I became interested in this research project after managing patients with infectious complications of immunosuppressant therapy, including TB.
My research involves comparing the effects of the anti-TNF antibodies (adalimumab and infliximab) with the soluble TNF receptor (etanercept), on antimycobacterial immune responses. This affords the opportunity for novel insights into the different immunologic correlates of protection in RA and TB.
As host defence against TB involves complex immunological networks, a novel approach for in vivo study of innate and adaptive anti-mycobacterial immune responses will be used, developed in Dr Noursadeghi’s lab. Genome-wide transcriptional profiling of skin punch biopsies at the site of Tuberculin skin tests, will provide the first in vivo human assessment of the effects of different anti-TNF therapies on mycobacterial responses within the tissue microenvironment.
Professor Ehrenstein’s group has shown that anti-TNF antibodies induce a potent population of regulatory T cells (Tregs), whereas etanercept does not. Existing literature suggests Tregs may attenuate host responses to TB at many levels, but the role of these cells in susceptibility to TB has not been tested, and would provide an entirely novel mechanism by which anti-TNF antibodies increase the risk of TB.
The ultimate aim would be to inform improved therapeutic targeting and therefore development of safer treatment for RA, identifying biomarkers to stratify TB risk during TNF blockade or other immunosuppressive therapies