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Clinical immunology: a whistle stop tour

Sofia GrigoriadouIn the first of a new series of articles for this magazine, I will start by setting out the initial steps for communicating the clinical aspects of immunology to the wider membership of the Society. Although the majority of our BSI community comprises of researchers, there are quite a few of us who do clinical work for a significant portion or the majority of our time. Given the breadth of work in immunology from bench to bedside, the BSI is keen to engage more with the clinical aspects of the discipline. This applies to multiple areas including training support and education, clinical practice, guidelines and clinical research. My personal ambition, as the new BSI Clinical Secretary, is to make this happen, with regular communication and networking with both clinicians and researchers.

What is a clinical immunologist?

I am a clinical immunologist and I am frequently asked the question, ‘what does a clinical immunologist do?’, so here is my answer…  Clinical immunologists are physicians involved in the care of patients with disorders resulting from the failure of the immune system (immunodeficiency) or immune dysregulation (allergy and autoimmunity). With respect to the former, we often deal with the human knock-outs of several immune pathways and are able to discover their significance in the ‘real world’. We are lucky to have already seen the rewarding results of the first gene therapy trials in humans; for example the recent announcement from Great Ormond Street that a young girl with leukaemia had been successfully treated with genetically engineered donor T cells and is now is remission. In the fields of autoimmunity, the use of monoclonal antibody therapies has revolutionised our ability to modulate the immune system and improve the quality of life of patients with conditions such as rheumatoid arthritis and ankylosing spondylitis. In allergy, we have seen great progress in desensitisation therapies, such as the work carried out at Addenbrooke’s Hospital in Cambridge on peanut allergy, and food desensitisation is now a reality. 

A varied day

Clinical immunology has been and still is a laboratory specialty, so a significant amount of our routine daily work includes laboratory work in relation to the diagnostics and monitoring of immunological diseases. We are involved in results validation and interpretation, quality assurance and assay development. In this aspect of our work, we seek to ensure the quality and reproducibility of diagnostic laboratory tests. This, in some ways, contrasts to the hypothesis driven tests performed at the research bench with unpredictable results. I would argue however that it is exactly the beginning of the patient’s care pathway where research findings apply to improve disease diagnostics. We liaise with other clinicians and specialties such as paediatricians, rheumatologists, respiratory physicians, nephrologists, GPs and infectious disease physicians to name just a few, and are very often asked to solve diagnostic enigmas and therapeutic dilemmas. Like other clinicians, we work in multidisciplinary teams with nurses in the clinic, but also biomedical scientists and clinical scientists in the laboratory. We are involved in research as well as undergraduate and postgraduate teaching. Much of our time is spent dealing with rare and perplexing diseases, meaning clinical trials are often scarce and solid evidence is often lacking. This means that we have to keep up-to-date with any literature available and often rely on networking with our colleagues. This paucity in data and rarity of conditions can also make the funding of new therapies challenging. In my view, clinical immunology is unique as it combines clinical and laboratory skills, providing the opportunity to improve our insight into the mechanisms underlying the evolution and complications of many immunologically-mediated disorders. The recent advances in genomics have contributed immensely to an ever expanding variety of diseases making the field a really exciting part of medicine. So for any of you who thought that we are simply sitting in offices behind a microscope reading slides all the time, this is simply not true! 

Current hot topics under discussion

Many clinical immunologists attend the biannual conference organised by the UK Primary Immunodeficiency Network, which focuses on primary immunodeficiency disorders (PID), the most recent of which took place in November 2015 in Belfast.  Among other conditions, there was focus on the auto-inflammatory syndromes, from the historic discovery of familial Mediterranean fever (an inherited disorder that causes recurrent fevers and painful inflammation of the joints and serous tissues lining the lungs, heart and abdomen) to the recently described gene defects in NLRC4, adenosine deaminase 2 (ADA2) and STING. Another new condition caused by gene overexpression, the activated PI3K-δ syndrome (APDS; which causes lymphopenia, recurrent respiratory infections and progressive lung damage) was also discussed in length including the promising therapeutic approach with mTOR inhibitors. Recent advances in whole genome sequencing (WGS) genomics were in the spotlight for much of this conference; NHS England Genomics 100,000 genomes project is underway and the immunology community is excited to participate in one of the clinical interpretation partnerships (GeCIP) for immunological and nonmalignant haematological disorders. This project brings together 128 immunology clinicians and scientists from around the country who are currently busy networking to make it happen. We are seeking to gain clinically relevant genomic data for our patients and their families and extend our knowledge and understanding of the genetic basis of PID and the function of the immune system. Inevitably the ‘great debate’ of the conference was on genomics and whether WGS will make diagnostic immunology redundant. We concluded that whilst we have learned a great deal about PID because of next generation sequencing, the immunology laboratory and functional tests will continue to play a fundamental role for the evaluation of these patients. If you missed this meeting, don’t worry – the next UK Primary Immunodeficiency Network meeting in 2017 will run sequentially with the BSI Annual Congress in Brighton, making it easier for research and clinical immunologists to come together to share ideas. I hope I have provided a flavour of what clinical immunologists do and some of the hot topics in our clinical practice. For those of you who are interested to learn more, have ideas you wish to share or news and updates which can bring clinicians and researchers together, please do not hesitate to contact me. 

Sofia Grigoriadou
BSI Clinical Secretary
Consultant Immunologist
Barts Health NHS Trust