Inborn Errors of Immunity Committee (IEI) - Activities

Newsletter Contribution, July 2019

It has been a very busy first half of the year for the IUIS IEI Committee, with much going on. In March, we held a face-to-face meeting at Rockefeller University, New York. The main goal of this meeting was to provide a critical review of the recent biomedical literature and identify and assess key publications that have reported novel genes that, when mutated, underlie monogenic immune dysregulatory conditions such as recurrent, severe and often-fatal infections, autoinflammatory disorders, autoimmunity, allergic disease and even cancer. Since we published the last update of genes causing inborn errors of immunity (2018), approx. 100 new genes have been reported to affect immunity. After rigorous discussion, the committee agreed on including about 70 of these. Thus, when our next update is published in 2020, we will report >400 genes as molecular defects underlying a vast array of monogenic immunopathologies.

The committee meeting was held at Rockefeller to take advantage of the annual meeting of the Henry Kunkel Society, which this year focussed on “New methods applied to inborn errors of human immunity: immunological and clinical impact”. As such, several of the committee members were presenters at this meeting (Jean-Laurent Casanova, Stuart Tangye), while many others attended.

(IUIS members attending our annual face to face meeting in NY, March 2029: L-R - Amos Etzioni, Hans Ochs, Charlotte Cunningham-Rundles, Jose Luis Franco, Jean-Laurent Casanova, Kate Sullivan, Troy Torgeson, Jennifer Puck, Talal Chatila, Stuart Tangye, Christoph Klien, Eric Oksenhendler, Waleed Al Herz; Absent: Capucine Picard, Aziz Bousfiha, Mini Tang, Steve Holland, Tomohiro Morio, Yanick Crow)

This meeting also was an opportunity to offer substantial thanks to several members who have decided to step down from the committee after many years of hard work, dedication and commitment. I would like to take this opportunity to give heartfelt thanks to the following retiring committee members:

  • Hans Ochs (USA)
  • Talal Chatila (USA)
  • Amos Etzioni (Israel)
  • Yanick Crow (UK/France)
  • Mimi Tang (Australia)

This enabled us to invite new members to join the committee. Nominations were sort and then voted. So I now very happy to welcome the following colleagues who were selected by their peers on the committee, and have graciously accepted our invitation to be part of a very dynamic and exciting committee:

  • Isabelle Meyts (Belgium)
  • Anne Puel (France)
  • Mikko Seppanen (Finland)
  • Raz Somech (Israel)
  • Helen Su (USA)

The immediate task for the committee is to finalise a paper detailing the latest update to the list of genes underlying inborn errors of immunity, which we will hopefully have published in the first quarter of 2020. We will next meet formally during the “2nd European Society for Immunodeficiencies (ESID) Focussed Meeting: PID and Malignancy” which will be held in September in Brussels, Belgium. Again, several committee members will be giving key presentations at this major meeting of the field of inborn errors of immunity. The committee will also be represented at the upcoming IUIS Beijing 2019 conference, with Kate Sullivan and Isabelle Meyts being invited participants and speakers.

Another important role of the committee is in educating and training clinicans, registrars, specialists, As such, many of us participate in various teaching courses to enable greater understanding of basic, clinical and translational immunology in general, but also to provide current updates and the latest information relating to developments in the field of inborn errors of immunity. Over the past few months, the following presentations have been given at the indicated meetings, courses, or teaching opportunities:

Aziz Bousfiha
- 6th ASID congress, Dakar, Senegal, April 2019: Phenotypical Classification of Primary Immunodeficiencies.

Stuart Tangye
- 47th Annual Scientific Meeting of the Australasian Society of Immunology, Perth, Australia, Dec 2018. Defects in human     lymphocyte differentiation in primary human immunodeficiencies.
- 27th Annual Henry Kunkel Society Meeting: New methods applied to inborn errors of human immunity: immunological and     clinical impact, Rockefeller University, New York, NY, USA. March 2019. Learning human immunology from the study of PIDs.
- IDFA (Immune deficiency Foundatin of Australia) Biennielle National Conference, Brisbane, Australia, April 2019. Genetic Testing for primary human immunodeficiencies
- International Day of Immunology, Garvan Institute, Sydney, Australia, May 2019. This is how immunology is great.
- Australasian Society for Clinical Immunology and Allergy (ASCIA) Primary Immunodeficiency Summer School, Sydney,     Australia, May 2019. I presented lectures on: (1) Basic science of B-cell disorders; (2) Basic science of combined immunodeficiencies; (3) PIDs associated with hyper-IgE; (4) Basic science of Immune dysregulation

Before I sign off, i would like to thank all of my committee colleagues – former, current and future – for making this a great collective of people working to provide an important service to the community. I am particularly grateful to past chairperson Kate Sullivan who always offers excellent advice, and Jose Luis Franco, who is a wealth of information and guidance. And also our project manager Antonis Pattakos. For those in the north, have a great summer; for those including myself in the southern hemisphere, I wish you warmth. And good health to everyone!

All the best

Stuart Tangye, PhD
Ph: +61 2 9295 8455
This e-mail address is being protected from spambots. You need JavaScript enabled to view it



Newsletter Report, December 2018

The IUIS Expert committee on Inborn Errors of Immunity has been very active recently. Several of our committee members have attended Summer Schools a teaching Faculty. These have included the ESID (European Society for Immunodeficiencies) Summer School (held in Pisa, Italy, May 2018 – Kate Sullivan), the Diagnostic School in Primary Immunodeficiencies School (held in Cincinnati, Ohio, US, July 2018 - Troy Torgerson), the Latin American Society for Immunodeficiencies (held in Medellin, Columbia, August 2018 – Jose Luis Franco, Stuart Tangye), and a Clinical Immunology Workshop held as part of the Australasian Society for Immunology annual conference (Perth, WA, Australia, Dec 2019 – Stuart Tangye). Our committee was also very well represented at the recent 18th Biennial meeting of ESID, held in Lisbon, Portugal, October 2018. Here, Jean-Laurent Casanova giving the opening Keynote address, Capucine Picard and Kate Sullivan gave presentations in the Educational Sessions, Capucine Picard and Steve Holland gave Plenary presentations, and Steve Holland (3 presentations), Talal Chatila, Capucine Picard, Kate Sullivan (2 presentations), and Stuart Tangye (2 presentations) all presented in parallel symposia sessions.
We also took advantage of many of the committee members attending the ESID meeting to hold an IUIS Committee meeting. This was well attended, with 15 committee members available. Several members have indicated that they will be stepping down from the committee over the next few months. So I would like to take this opportunity to thank Mimi Tang, Hans Ochs, Talal Chatila and Amos Etzioni for their invaluable contributions to the IUIS Expert Committee over the past several years. One of the key agenda items of this recent meeting was identifying and recruiting appropriate new committee members to replace these outgoing individuals, and to also make sure we strive to have a committee with sufficient geographical, expert and gender representation and composition. New members of the committee will be announced in future IUIS newsletter reports.
The Expert committee on Inborn Errors of Immunity is looking to leverage its relationships with IUIS to advance our activities. There are two major opportunities through which we are working to achieve this. First, interact with other IUIS committees, the most obvious ones would be the Clinical Immunology Committee, Publications Committee, Education Committee, and Gender Equality & Career Development Committee. As chair, I am in the process of establishing dialogues with the chairs of these other committees. Second (which is an extension of one of the firsts) is to contribute to publications by Frontiers in Immunology, as it is recognised as the official journal of IUIS. Fortunately, we are well positioned to achieve this, with an opportunity to contribute to a Research Topic on “Applications of Flow Cytometry to Primary Immunodeficiencies”.
The next major objective of the IUIS Expert committee on Inborn Errors of Immunity is the organization of the 2019 face-to-face meeting. This meeting will be held at Rockefeller University in New York just before the annual Henry Kunkel Society meeting in March 2019. The goal of this meeting will be for us to review all of the recently-published genetic defects underlying immune dysregulatory conditions in order to collate these into the next Phenotypic and Genetic classifications of primary immunodeficiencies/inborn errors of immunity, which will be published in late 2019/early 2020. There are currently 354 inborn errors of immunity, due to loss or gain of function mutations in ~330 genes. With the explosion in the rate of detection of gene defects underlying monogenic inborn errors of immune dysregulation by next generation sequencing technologies, the number of genetic etiologies will easily exceed 400. So the committee will be very busy discussing these findings.
Additional upcoming activities for the IUIS Expert Committee and its members on Inborn Errors of Immunity includes:
• Working with the Clinical immunology committee to support educational activities
• educational initiatives, including participation in the 2019 Clinical Immunology Society (CIS) annual meeting and pre-conference education day;
• attendance at the IPOPI (International Patient Organisation for Primary Immunodeficiency)/IPIC (International Primary Immunodeficiency Congress) meeting to be held in Madrid in November 2019;
• continuing liaising with IUIS to ensure participation and representation of our committee members, as well as an appropriate symposium session on Inborn errors of immunity, at the IUIS meeting to be held in Beijing in 2019.




Newsletter Report, June 2018

This is my first newsletter in the capacity as Chair of the IUIS Expert Committee on Inborn Errors of Immunity (previously Primary Immunodeficiencies). I joined this committee in 2015, at a time when Prof Bobby Gaspar (Great Ormond St Hospital, London, UK) was Chair. Bobby was succeeded by Prof Kate Sullivan (Children’s Hospital of Philadelphia, USA) in 2016, and it was with great excitement (and some trepidation) that I was invited to succeed Kate earlier this year. I have greatly enjoyed being on this committee and really appreciated the excellent leadership of both Kate and Bobby, from whom I have learnt a great deal – I know that I have large shoes to fill.


I thought I would take this opportunity to introduce myself to IUIS. Unlike many previous chairs (and even members) of our committee, I am not a clinician – however, I have always had a great passion for human immunology. Like the careers of many individuals, numerous serendipitous events lead me to study primary immunodeficiencies – as such, I have been working in this field for nearly 20 years now, firstly focusing on a single inborn error of immunity (SH2D1A, which is mutated in X-linked lymphoproliferative disease) but now we study a very broad range of primary immunodeficiencies to understand the requirements for generating effective immune responses in humans but also to elucidate mechanisms of disease in affected individuals. I have been fortunate to collaborate with, and benefit from the generosity and collegiality of, many former and current members of the IUIS Expert Committee on Inborn Errors of Immunity. Thus, being invited to join this committee was very humbling and rewarding, and becoming the Chair represents a great opportunity for me to continue the outstanding work the committee and previous Chairs have done for over the past 3 decades.

The IUIS Expert Committee on Inborn Errors of Immunity committee is tasked with maintaining a list of immunologic disorders. The rate of discovery of genetic variants underlying immune dysregulatory conditions – infection, autoimmunity, allergy, malignancy – continues remarkable. his has been facilitated by the access to and affordability of next generation sequencing (NGS) technologies and platforms that enable unbiased and rapid detection of genetic variants in affected individuals and the ability to establish causation and contribution of these variants to disease pathogenesis. The explosion in discovery of inborn errors responsible for novel immunological diseases of the immune system is illustrated in the graph below. This depicts the annual accumulated number of genes identified that, when mutated, cause disease. In 2011, ~200 gene defects had been identified, and this was almost exclusively through targeted/traditional approaches such as linkage analyses, homozygosity mapping, and sequencing candidate genes. Today, >350 gene defects have been discovered, with the vast majority of these being resolved by NGS approaches, such as whole exome and whole genome sequencing. In the last 18 months alone, >50 gene defects have been discovered – with more and more centers routinely performing NGS, and even incorporating this into the work up of patients with atypical clinical presentations, this number and rate of discovery will only increase in the weeks, months and years ahead.


The reason I am emphasizing this is because one of the major goals of the committee is to judiciously assess the reporting of novel variants and maintain a detailed and current list of primary immune dysregulatory conditions. The most recent update was published in January in the Journal of Clinical Immunology – this is a key resource for the fields of clinical and basic immunology, evidenced by this publication being dowloaded >5000 times. As this list of gene defects is routinely used as a reference to categorise and predict the pathogenicity of variants identified in patients by NGS, it is imperative for us as a committee to remain abreast of reportings of all genetic defects attributed to causing immunological diseases. Due to the rapid rate of publication of novel gene defects, we are thus committed to providing an update to the list of gene defects every 6 months – this update is available on the IUIS website


Upcoming activity for the IUIS Expert Committee and its members on Inborn Errors of Immunity includes:

  • a meeting held as part of the 18th Biennial Meeting of the European Society of Immunodeficiencies in October 2018;
  • the major biennial meeting in February 2019 where content of the next published update of the genetic and phenotypic classification of Inborn Errors of Immunity will be ratified.
  • working with the Clinical immunology committee to support educational activities
  • educational initiatives, with several members of the committee attending as teaching faculty at the LASID (Latin American Society of Immunodeficiencies) Summer School, to be held in Medellin, Columbia in August 2018
  • attendance at the Jeffrey Modell Foundation Primary Immunodeficiency meeting, to be held in New York in September 2018, providing opportunities
  • liaise with IUIS to ensure participation of our committee members, as well as an appropriate symposium session on Inborn errors of immunity, at the IUIS meeting to be held in Beijing in 2019.

Prof Stuart Tangye
Garvan Institute of Medical Research, NSW, Australia


Last meetings, February 2017

During its last meeting in February 2017, the committee began the work of updating the list of disorders.  Historically, the list has been published as a journal article and that will be forthcoming.  However, in acknowledgement of digital sources offered by IUIS and the need for a more nimble approach, this list is now available for direct download on the IUIS web site. This list can be used to design sequencing panels, ICD code lists and diagnostic algorithms.  The download list also allows sorting by gene name and inheritance when opened using a database application such as Excel.




Current activities

  • To review national and international guidelines for the diagnosis and or management of immune deficiencies by expert groups on request. Liaison – Luigi Notarangelo
  • To assist with the revision of diagnostic criteria for primary immunodeficiencies with the IUIS Clinical Immunology committee and the European Society for Immune Deficiencies. Liaison – Mary Ellen Conley
  • To produce a simplified version of the IEI Classification Tables for the general public. Liaison – Aziz Bousfiha
  • To assist Orphanet and the World Health Organisation in the revision of the International Classification of Diseases (ICD) codes for the primary immune deficiencies, version 11, due to be published in 2015. Liaison – Mimi Tang
  • To ensure the continued inclusion of therapeutic immunoglobulin in the World Health Organisation Essential Medicines Lists. Liaison – Jose Franco
  • To encourage, with the International Patient Organisation for Primary Immunodeficiencies, the implementation of the recommendations from the IUIS IEI position paper on the Safety and Availability of Immunoglobulin (1999) including: the avoidance of blood donation by individuals who have received blood or blood products in the past; recording of all batch numbers for tracing in the event of any pathogen transmission; to attempt (with the patient organisations) to obtain ante-mortem permission for post-mortem examination in all patients with primary immune deficiencies in countries in which post-mortem examinations are permitted; to consider advice on the routine immunisations needed for patients with primary immune deficiencies. Liaison – Jose Franco




Previous activities

  • Report on classification of IEIs published biennially since 1973. Latest version (2009) is available online
  • Availability of immunoglobulin – Successful application to WHO Essential Medicines List 2007 and WHO Essential Medicines List for Children 2008
  • Safety of immunoglobulin therapies – Position paper published in Clinical and Experimental Immunology in 1999


Relationship with IUIS

The IEI committee liaises with the following IUIS committees:

  • IUIS Committee on Clinical Immunology - particularly in relation to diagnostic criteria and availability of new therapies – Liaison -Mary Ellen Conley
  • IUIS Committee on Education - advertisement of schools for young investigators run by European Society for Immune Deficiencies (winter, spring and summer schools), US Clinical Immunology Society, Latin American Group for Immune Deficiencies and the S Asia Pacific group; facilitation of exchange of students from different regions; to encourage new groups such as the Federation of African Immunological Societies to establish similar educational opportunities for IEIs
  • IUIS Committee on Quality Assessment and Standardization – particularly in relation to QA for diagnostic procedures in IEIs, such as test immunization responses.


We are grateful to the following for their support, without which the committee would not be able to meet these responsibilities:
Baxter Healthcare, Octapharma, Grifols, Talecris and CSL-Behring.