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CEI at 55: Key advances in translational immunology

2021 marks the 55th anniversary of the British Society for Immunology’s journal Clinical & Experimental Immunology (CEI). Here, we explore the contribution of the journal to the advancement of immunological knowledge from the perspective of each of CEI’s dedicated Section Editors, who are experts in the fields of autoimmunity, immune-mediated inflammatory diseases, cancer immunity, infectious diseases, immunodeficiency and neuroimmunology.

AutoimmunityAnchor

Professor Angelo Manfredi, Università Vita-Salute San Raffaele, Italy

Figure from Establishing the prevalence of common tissue-specific autoantibodies following severe acute respiratory syndrome coronavirus 2 infection

Given the journal's mission to integrate clinical information and basic immunology, it is not surprising that CEI has consistently been a privileged forum for authors who actively and passionately study autoimmunity. Reading back, the novelty and breadth of the studies published in the first decades of the journal's life are impressive, as can easily be seen by those on the role of autoantibodies in redesigning the nosology of adrenal insufficiency1 or by the precocious insights into the role of activation of the complement cascade both in providing clues to the pathogenesis of systemic lupus erythematosus and as a marker indicating “occult disease activity”2.

The bold attempt to integrate information on innate and acquired immunity, humoral and cellular responses, experimental and clinical studies to obtain the keys to understanding human autoimmune diseases has been a constant feature of autoimmunity studies throughout the 55 years of the life of CEI. The field is far from exhausted, with scientists striving to configure elegant molecular models of diseases with the results obtained from increasingly informative and high-throughput approaches, our September Editors’ Choice paper being a great example of this3, among many others4–7.


  1. Irvine WJ, Stewart AG, Scarth L. 1967 A clinical and immunological study of adrenocortical insufficiency (Addison's disease). Clin Exp Immunol 2, 1–70
  2. Glennon-Alty L, Moots RJ, Edwards SW, Wright HL. 2021 Type I interferon regulates cytokine-delayed neutrophil apoptosis, reactive oxygen species production and chemokine expression Clin Exp Immunol 203, 151–9

Immune-mediated inflammatory diseasesAnchor

Professor Ciriaco Piccirillo, Department of Microbiology and Immunology, McGill University, Canada

An effective inflammatory response relies upon intricate cellular and molecular interactions between the immune system, the vascular system and the tissue. It is equally important that inflammation is resolved; when inflammation is not properly controlled, it can eventually result in immune-mediated inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis, transplant rejection or impaired wound healing. Inflammation is also recognised increasingly as a contributor to cancer, neurodegeneration, long-term pain and certain psychiatric and mental health disorders. 

Figure from IL-17 in inflammatory skin diseases psoriasis and hidradenitis suppurativa

In its 55-year life, CEI has published many notable papers on the subject, including a 1995 study on Th1/Th2 cytokine profiles in inflammatory bowel disease which revealed that a relative under-expression of cytokines could be equally important as cytokine over-expression in inflammatory disease pathogenesis1. Other highly-cited publications from the journal's archive have further explored this cytokine imbalance in diverse immune-mediated inflammatory conditions2–4. We're continuing to publish key research in this area, a prime example being a recent review on the role of IL-17 in inflammatory skin diseases5, which was one of our top Altmetric score articles of 2020.

 


  1. Niessner M, Volk BA. 1995 Altered Th1/Th2 cytokine profiles in the intestinal mucosa of patients with inflammatory bowel disease as assessed by quantitative reversed transcribed polymerase chain reaction (RT-PCR). Clin Exp Immunol 101, 428–35
  2. Reinecker et al. 1993 Enhanced secretion of tumour necrosis factor-alpha, IL-6, and IL-1 beta by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn's disease Clin Exp Immunol 94, 174–81
  3. Deviere et al. 1989 High interleukin-6 serum levels and increased production by leucocytes in alcoholic liver cirrhosis. Correlation with IgA serum levels and lymphokines production Clin Exp Immunol 77, 221–5
  4. Dieleman et al. 1998 Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines Clin Exp Immunol 114, 385–391
  5. Fletcher JM, Moran B, Petrasca A, Smith CM. 2020 IL-17 in inflammatory skin diseases psoriasis and hidradenitis suppurativa Clin Exp Immunol 201, 121–134 

ImmunodeficiencyAnchor

Dr Cindy Ma, Garvan Institute of Medical Research, Sydney, Australia

As we look back on the 55th anniversary of Clinical & Experimental Immunology and reflect on the significant developments in the field of primary immunodeficiency, one advance stands out – the advent of next generation sequencing (NGS) and its application to diagnosing inborn errors of immunity (IEI). This is reflected in the report written by the International Union of Immunological Societies (IUIS) Expert Committee on Primary Immunodeficiencies/IEI, which has revised the classification of primary immunodeficiencies every two years since the early 1970s. 

Figure from Mimicking Behçet’s disease: GM‐CSF gain of function mutation in a family suffering from a Behçet’s disease‐like disorder marked by extreme pathergy

Indeed, when these reports were published in CEI in 1999 and 20031–2, ~100 genes had been identified to cause IEI in the ~30 years since the publication of the first report in 1970. With the rapid advances in NGS technologies, conventional molecular techniques such as genetic linkage, homozygosity mapping and candidate gene sequencing have essentially been abandoned, making way for the almost-ubiquitous application of NGS to the unbiased discovery of known and novel genetic causes of immune dysregulation. Since the introduction of NGS in 2010 there has been exponential growth in the identification of genes as the underlying cause of IEI, with the most recent version of the IUIS report published in 2020 documenting 430 genes3.

Along with this, there has been a sharp rise in the number of primary immunodeficiency articles submitted to CEI which has led to my appointment as the journal’s first Immunodeficiency Section Editor last year. This year to mark World Primary Immunodeficiency Week, the journal published its first primary immunodeficiency Virtual Issue which highlights reviews and original research from the last three years, focusing on topics including PID diagnosis and pathogenesis in chronic granulomatous disease, Behçet’s disease and other PIDs, as well as clinical guidelines on the management of non-infectious CVID complications from the UK Primary Immunodeficiency Network. With the support of my international Section Editorial Board encompassing a wealth of knowledge in the field, we are ready and looking forward to seeing more primary immunodeficiency themed articles submitted to CEI.


  1. 1999 Primary Immunodeficiency Diseases Report of an IUIS Scientific Committee Clin Exp Immunol 118, 1–28
  2. Chapel H, Geha R, Rosen F 2003 Primary immunodeficiency diseases: an update Clin Exp Immunol 132, 9–15
  3. Bousfiha et al. 2020 Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification J Clin Immunol 40, 66–81

Cancer immunity

AnchorProfessor Tanja de Gruijl, VU University Medical Centre, Netherlands

When Dr Jim Allison wrote his review ‘Cancer Immunotherapy: co-stimulatory agonists and co-inhibitory antagonists’1 in Clinical & Experimental Immunology way back in 2009, our readers could not have surmised the revolution that his seminal work was about to unleash on the field of oncology. The unprecedented durable responses observed in metastatic melanoma upon CTLA-4 blockade reported only one year later, and the even more remarkable survival rates obtained with PD-1 inhibitors that would closely follow, led to immunotherapy of cancer being heralded the scientific breakthrough of the year in 2013 and to the Nobel prize being awarded to Dr Allison and Professor Tasuku Honjo in 2018.

Since then, exciting new developments in the field of cancer immunology provide us with glimpses of things to come. New findings, like the identification of additional immune checkpoints, the unravelling of the mechanisms of action of immune checkpoint inhibitors, and the mechanisms underlying immune suppression and immune therapy resistance – both systemically and in the tumour microenvironment – are set to increase the clinical efficacy of cancer immunotherapy in an ever-increasing number of indications. In the near future, novel treatment combinations and local delivery of immune modulators in earlier stages of disease should widen the scope and deepen the impact of this ongoing revolution. Naturally, Clinical & Experimental Immunology is committed to keeping our readers up to speed with these important developments.


  1. Peggs KS, Quezada SA, Allison JP 2009 Cancer immunotherapy: co-stimulatory agonists and co-inhibitory antagonists Clin Exp Immunol 157, 9–19
  2. Oleinika K, Nibbs RJ, Graham GJ, Fraser AR 2013 Suppression, subversion and escape: the role of regulatory T cells in cancer progression Clin Exp Immunol 171, 36–45
  3. Whiteside TL. 2017 Exosomes carrying immunoinhibitory proteins and their role in cancer Clin Exp Immunol 189, 259–267
  4. Taams LS, de Gruijl TD 2020 Immune checkpoint inhibition: from molecules to clinical application Clin Exp Immunol 200, 105–107
  5. Harjunpää H, Guillerey C. 2020 TIGIT as an emerging immune checkpoint. Clin Exp Immunol 200, 108–119
  6. ElTanbouly MA, Schaafsma E, Noelle RJ, Lines JL. 2020 VISTA: Coming of age as a multi‐lineage immune checkpoint Clin Exp Immunol 200, 120–130
  7. Hill et al. 2020 Role of inflammasome activation in tumor immunity triggered by immune checkpoint blockers Clin Exp Immunol 200, 155–162
  8. Vukovic N, van Elsas A, Verbeek JS, Zaiss DMW 2021 Isotype selection for antibody-based cancer therapy Clin Exp Immunol 203, 351–365

Infectious diseasesAnchor

Professor Xiao-Ning Xu, Imperial College London, UK

Dr Daniel Douek, National Institute of Allergy and Infectious Diseases/National Institutes of Health/DHHS, USA

Figure from Vaccines for COVID-19

The concept of immunology, and in particularly vaccinology, was originally derived from the field of infectious diseases and is largely attributed to Edward Jenner who experimentally discovered in 1796 that cowpox, or vaccinia, induced protective immunity against a human fatal infection – the smallpox. Since then, studies of infectious diseases have informed our knowledge of many aspects of the immune system. Studies investigating the roles of antibodies in Epstein-Barr virus (EBV)-associated cancers1, and later the role of T cells, have provided a base for the development of immunotherapies for EBV-induced cancers. Furthermore, many studies have revealed the role of tumour necrosis factor in mediating harmful hyperinflammatory responses observed in many infectious diseases2–3. Clinical & Experimental Immunology has also made an important contribution to HIV/AIDS research over the years, by publishing several highly-cited papers on key aspects of the immune response to HIV4–5.

The exponential growth in our knowledge of immunology is evidenced by the rapid development of effective vaccines against the current SARS-CoV-2 pandemic. Clinical & Experimental Immunology has been proud to publish some of the crucial research helping us understand and combat SARS-CoV-2, a key example being our COVID-19 Special Issue, which reflected on our understanding of the pathogen after one year of research. We’re continuing to publish key research on this topic, including our recent Editors’ Choice article on the prevalence of tissue-specific autoantibodies following SARS-CoV-2 infection6.


  1. Schryver et al. 1969 Epstein–Barr virus-associated antibody patterns in carcinoma of the post-nasal space Clin Exp Immunol 5, 443–459
  2. Kwiatkowski et al. 1989 Tumour necrosis factor production in Falciparum malaria and its association with schizont rupture Clin Exp Immunol 77, 361–366
  3. Moreno et al. 1989 Lipoarabinomannan from Mycobacterium tuberculosis induces the production of tumour necrosis factor from human and murine macrophages Clin Exp Immunol 76, 240–245
  4. Autran et al. 1989 T cell receptor gamma/delta+ lymphocyte subsets during HIV infection Clin Exp Immunol 75, 206–210
  5. Stylianou et al. 1999 IL-10 in HIV infection: increasing serum IL-10 levels with disease progression—down-regulatory effect of potent anti-retroviral therapy Clin Exp Immunol 116, 15–120
  6. Richter et al. 2021 Establishing the prevalence of common tissue-specific autoantibodies following severe acute respiratory syndrome coronavirus 2 infection Clin Exp Immunol 205, 99–105

NeuroimmunologyAnchor

Figure from Neuroimmunology – the past, present and future

Professor Sandra Amor, VU University Medical Centre, Netherlands

Although the brain is widely considered to be an immune-privileged organ and immune responses in the CNS limited1, there has been a paradigm shift in neuroimmunology as reflected by some key papers in the field. The (re)discovery of a glymphatic system in the CNS has proven to be critical in removing aggregated aberrant proteins such as amyloid beta that contribute to Alzheimer’s disease2,3. Knowledge of the innate immune responses in the CNS has also highlighted a critical role in tissue homeostasis, as well as contributing to CNS damage4. While several papers published have documented how immune responses contribute to multiple sclerosis5, others have highlighted the critical role of innate immune responses in neurodegenerative diseases such as Alzheimer’s disease1, psychiatric diseases6 and more topically, in COVID-197.


  1. Nutma E, Willison H, Martino G, Amor S. 2019 Neuroimmunology – the past, present and future Clin Exp Immunol 197, 278–293
  2. Louveau et al. 2015 Structural and functional features of central nervous system lymphatic vessels Nature 523, 337–341
  3. Tarasoff-Conway et al. 2015 Clearance systems in the brain-implications for Alzheimer disease Nat Rev Neurol 11, 457–470
  4. Stephenson J, Nutma E, van der Valk P, Amor S. 2018 Inflammation in CNS neurodegenerative diseases Immunology 154, 204–219
  5. Baker D, Marta M, Pryce G, Giovannoni G, Schmierer K. 2017 Memory B Cells are Major Targets for Effective Immunotherapy in Relapsing Multiple Sclerosis EBioMedicine 16, 41–50
  6. Mondelli V, Vernon AC 2019 Early adversities to immune activation in psychiatric disorders: the role of the sympathetic nervous system Clin Exp Immunol 197, 319–328
  7. Amor S, Fernández Blanco L, Baker D. 2020 Immunity during SARS-CoV-2: evasion strategies and activation trigger hypoxia and vascular damage Clin Exp Immunol 202, 193–209

You can read more about Clinical & Experimental Immunology’s 55th anniversary celebrations in our news section.