It is jarring to reflect on the fact that the world has been experiencing the COVID19 pandemic for nearly 3 years now. 65 million cases of infection and > 6 millions deaths is sobering. Understanding and managing emerging diseases – especially in the context of at-risk populations – really highlights some of the fundamental roles that the IUIS Committee for Inborn Errors of Immunity can have in the fields of infectious diseases, immune dysregulation, genetics of human disease, as well as social equity for access to vaccines.
Over the past 18 months, our committee has published 3 peer-reviewed scientific papers in the Journal of Clinical Immunology. These papers provide updates to community on monogenic causes of diseases of the immune system. These conditions can manifest clinically as increased susceptibility to infectious disease, autoimmunity, autoinflammation, allergic and even cancer. We strive to publish these updates every 2 years – with COVID upon us, it was decided to publish an interim update in 2021.
This reported 26 new types of inborn errors of immunity, including several underpinning severe and often fatal SARS-CoV2 infection and COVID19.
More recently, the biennial papers have been published or accepted for publication. The first of these (Tangye et al) provided a comprehensive overview all ALL genetic causes of inborn errors of immunity, as well as highlighting the novel inborn errors that had been published since the previous update (published in 2020) or that had been published earlier again but more evidence had been provided to confirm the pathogenicity of these genetic vairants. Our previous update, published in January 2020, reported 430 gene defects responsible for these conditions. The latest publication has increased this to 485 genetic causes of human immune diseases. This increase reflects the dynamic nature of the field, and ready-access to next generation DNA sequencing technologies, and the capacity to perform functional genomic assays to establish that coding changes in specific genes can indeed be pathogenic, and thus disease causing.
Fig. 1 Accumulative discovery of novel inborn errors of immunity: 1980–2022. (A) The number of genetic defects underlying monogenic immune disorders as reported in the indicated year. (B) The number of pathogenic variants listed in each Table of the IUIS IEI committee 2022 report. The numbers in each column correspond to the number of genes reported in the 2019 IUIS update (blue bars), the number of new genes for each category/table (1 though 10) (red bars), and the total number of genes for each category/Table (black number).
The second and companion article (Bousfiha et al, The 2022 update of IUIS Phenotypical Classification for Human Inborn Errors of Immunity) is currently in press and should be published online any day now! This paper continues the outstanding work of committee member Prof Aziz Bousfiha and his colleague Dr Leila Jeddane in Morocco, and diagrammatically categorises inborn errors of immunity according to clincal phenotype.
These 2 papers are incredibly valuable resources for clinical immunologists and non-specialists as they provide detailed updates of genetic causes of immune diseases, as well as assist in the differential diagnosis of these conditions. The value of these articles is reflected in the number of times they are viewed online and cited in the literaure. For instance, the updates published in 2020 by the committee (Tangye et al J Clin Immunol; Bousfiha et al J Clin Immunol) have collectively been viewed >100 000 times and have been cited >900 times over the past 2 years; the 2021 Interim Update has been accessed >16 000 times and cited in 88 publications already. It is anticipated that these 2022 publications will have a similar impact on the field.
Over the past few months, members of the committee have been very active in the area of presenting latest findings at key clinical immunology meetings. Updates from these classification publications have been presented by:
• Dr Leila Jeddane and Prof Aziz Bousfiha at the 7th congress of ASID (African Society of Immunodeficiencies), October 2021,
• Stuart Tangye at UK PID Registry meeting, sponsored by Takeda (December 2021),
• Stuart Tangye at the Royal College of Pathologists Annual Meeting (April 2022),
• Steve Holland at the IPOPI meeting, Portuga, April/May 2022,
• Stuart Tangye at 13th Kanto Kouetsu Immunodeficiency Study Group meeting, Japan (Sept 2022)
Several members of the IUIS IEI EC will also be attending and giving major presentations at the upcoming Biennial European Society for Immunodeficiencies (ESID) Meeting, being held in person (frst time since 2019) in Gothenburg, Sweden in October. Presentations will be given by Stuart Tangye Isabelle Meyts, Steve Holland and Anne Puel.
The IUIS IEI EC continues to be incredibly active in the COVID19 space, particularly Helen Su who co-leads the COVID Human Genetic Effort. This global consortium has made major inroads into dissecting the molecular and serological causes of severe COVID19 in ~15-25% of individuals. Members of the COVID HGE who are also members of the IUIS committee include Aziz Bousfiha, Isabelle Meyts, Jose Luis Franco, Anne Puel, Tomohiro Morio, Mikko Seppänen and Stuart Tangye.
Lastly, I would like to thank all of my committee colleagues for making this a great collective of people working to provide an important service to the community. I would particularly like to recognise the efforts over many years of our colleagues who have decided to stepped down from the committee: Jennifer Puck, Erik Oksenhendler, Steve Holland and Jose Luis Franco. I will also be stepping aside as Chair and handing over to Isabelle Meyts for the next iteration of the Committee.
All the best
Stuart Tangye, PhD
Ph: +61 2 9295 8455
