Newsletter 02






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Dear *|FNAME|*

This is the second newsletter of the 18th International HLA and Immunogenetics Workshop with the aim to update you on various aspects of the workshop, including updates on the organization, project highlights, and component updates of the 18th IHIWS.
For those who will attend the EFI conference this week in Lisbon, please note the availability of a number of project leaders.  

Sebastiaan Heidt
Eric Spierings

Newsletter content

  • EFI conference announcement
  • Meeting epitope component
  • IHIWS database
  • Official Workshop Partners
  • Project in the Spotlight
  • Australian hub: Loyd D’Orsogna

EFI conference announcement

A number of project leaders will have a project meeting during the 33rd EFI Conference in Lisbon. Below, you can find a schedule. If you are interested in joining one of these meetings, please contact the project leaders for time and location. Note that rooms for these meetings have a limited capacity.

Component Organisers Email
Immunogenetics of Ageing Milena Ivanova and Elissaveta Naumova mivanova@intech.bg
HLA-TCR interaction  Sami Djoulah sami.djoulah@wiratech.com
Population genetics, anthropology and evolution Alicia Sanchez-Mazas and Natasja de Groot alicia.sanchez-mazas@unige.ch
High-resolution KIR in populations Jill Hollenbach and Paul Norman jilll.hollenbach@ucsf.edu
Creating Fully Representative MHC Reference Haplotypes Paul Norman paul.norman@ucdenver.edu
HLA-DQ Immunogenicity Lloyd D’orsogna Lloyd.D’Orsogna@health.wa.gov.au

Meeting of the epitope component

On the 14th of November 2018, a meeting was organised in Leiden, the Netherlands with the project leaders of the various epitope component projects of the 18th IHIWS. Present were Peter Nickerson (Canada), Vasilis Kosmoliaptsis (UK), Anat Tambur (USA), Frans Claas, Cynthia Kramer, Sebastiaan Heidt and Eric Spierings (all from the Netherlands). Unfortunately, René Duquesnoy (USA) had to cancel his attendance.
The main topics discussed were on the definition of the various epitope projects for the 18th IHIWS and the minimal and ideal data requirements for these projects. In total, four projects were identified:

  • Immunogenic epitopes: define the epitopes which most often lead to antibody formation
  • Non-immunogenic epitopes: define epitopes that do not lead to antibody formation
  • HLA-DQ immunogenicity: subgroup analysis of patients receiving 2 HLA-DQ mismatches with de novo DSA to only one mismatched HLA-DQ allele
  • Manitoba project

These projects were discussed in depth, especially on which minimal datasets and quality were deemed required and achievable. Based on the discussion, project descriptions have been made and can be found on the IHIWS website. Currently, the database infrastructure is being built to accommodate data collection. Hereby, we would like to invite you subscribe to the various epitope projects. To do so, please visit the IHIWS website.

IHIWS database

The transfer of the 17th Workshop Database infrastructure from a local server to a cloud-based environent is on its way. While we initially considered a transition in database structure from Oracle to SQL-based database, it appeared too time-consuming at this stage. Moreover, adaptations are required to better serve the Antigenicity & Immunogenicity Components. We expect to have the basic database infrastructure up and running before this summer and will update you in the next newsletter.

Official Workshop Partners

In the last two months, we welcomed two new Official Workshop Partners; Omixon and the Dutch Transplant Society. With their contributions, we can further support the Workshop activities. More partners are about to join in and we hope to update you soon. Note that Partnership with the Workshop is based on an all-inclusive philosophy with the aim of helping our field forward. We are therefore grateful to GenDxImmucorPIRCHE, Omixon, and the Dutch Transplant Society for their contributions.

Project in the Spotlight

This time, we highlight the project Immunogenetics of Ageing organised by Elissaveta Naumova, Milena Ivanova, Graham Pawelec.

Deterioration of the immune system with aging is associated with an increased susceptibility to infectious diseases, cancer and autoimmune disorders. Many studies have focused on age-associated changes in immune functions which might contribute to these pathologies. It has been demonstrated that aging is associated with chronic, low-grade inflammatory activity. The aging process is very complex and longevity is a multifactorial trait, which is determined by genetic and environmental factors, and the interaction of “disease” processes with “intrinsic” ageing processes. It is hypothesized that the level of immune response as well as possibly longevity could be associated with genes regulating immune functions. It is further hypothesized that the diversity of these genes might influence successful aging and longevity by modulating an individual´s response to life-threatening disorders. Several studies have focused on the role of immune gene polymorphisms for human longevity. However, available data do not allow at present to clarify the role of these genes due to major methodological problems, such as the typing approach and focusing on single loci, insufficient sample size, different inclusion criteria and age limits, inappropriate control matching and neglected considerations of sex-related effects and the different genetic make-up of studied populations.

The aim of the component “Immunogenetics of Ageing” is to identify new biomarkers for successful aging and an increased capacity to reach the extreme limits of life-span by analysis of immune response genes. Within 18th IHIW we plan to confirm and clarify the functional relevance of the possible biomarkers, defined in previous workshops, in a larger cohort of healthy elderly, elderly patients with age-associated diseases and controls (young and middle age) from different populations
The study will include unrelated elderly individuals (octogenarians and nonagenarians) and families with longevity members. The following selection criteria will be used to identify families for the study:

  • extended families with a family history of at least two generations with longevity members (octogenarians and nonagenarians) including: elderly individuals, their children and grandchildren
  • sufficient demographic data should be available 
  • data on family history of diseases should be available

Elderly individuals (in family-based analyses and unrelated case-control analyses) selected should ideally be characterized according to the SENIEUR or nearly – SENIEUR protocols.

Ethnically matched unrelated young controls should ideally be characterized according to JUNIER protocol. Ethnically matched middle aged controls will also be included in the study.

Comparisons with young and middle – aged controls will be performed. The project will be focused on the following candidate biomarkers: classical HLA loci (HLA-A,-B,-C,-DRB1/3/4/5, -DQB1,-DQA1, -DPA1, -DPB1), genes in the extended MHC region such as MICA and MICB, polymorphisms in pro- and anti-inflammatory cytokine genes (IL-2, IL-6, IL-10, IL-12, IFNγ, TNFα, TGFβ) with possible correlation to the level of gene expression, KIR, BCR and TCR. Linkage and Association analyses and correlation with functional parameters, defining immune risk profiles will be performed. Additionally relevant markers will be analyzed in well characterized cell clones from elderly and controls, collected and established during the previous projects focusing on immunosenescence and aging.

To declare your interest to join this Component, please fill the form on the 18th IHIW website at https://www.ihiw18.org/component-ngs-for-hla/aging/.  

Presenting our Australian IHIWS hub: Lloyd D’Orsogna

It is my honour to serve as an Australian based hub for the 18th IHIWS which will take place in the Netherlands 2021. I was first introduced to the international HLA community through the 2006 immunogenetics summer school and it is a scientific group I have been proud to be an active member of ever since. I hope my contribution to the workshop will help benefit our scientific community, and our transplant patients, as we enter this new and rapidly changing era of transplantation immunology.

I received my medical degree from the University of Western Australia in 1999 and entered internal medicine training. In 2003 I was rostered to work in the Department of Clinical Immunology under the supervision of Prof Frank Christiansen, and quickly decided that Transplantation Immunology and HLA would become my life’s work! To pursue this possibility, I left my clinical position and enrolled in PhD studies under the supervision of Prof Frans Claas at the Leiden University Medical Centre. Research performed in Leiden focused on crossreactivity of virus-specific memory T-cells against allogeneic HLA molecules, and I was extremely honoured to receive the prestigious Julia Bodmer award 2011 for the work undertaken in the Leiden group. Since returning to Australia I have completed specialist training in both Clinical Immunology and Pathology and am currently employed as an Immunologist and the ASHI director for the transplant laboratory at Fiona Stanley Hospital in Perth, Western Australia. 

A new era of personalized recipient and donor matching is on the horizon. While the Human Leucocyte Antigen (HLA) complex is the major immunological barrier to transplantation, the simple assumption that each HLA mismatch has equal weight has proven not to be true. Patients transplanted with many HLA antigen mismatches may do well and whereas much better HLA matched grafts can fail, and the immunogenicity of individual HLA mismatches may differ. I am currently pursuing studies with the aim to benefit the hard to match recipient such as individuals with homozygosity, rare HLA antigens and the highly sensitised transplant recipient, an interest which has developed from our involvement in transplantation for the native Australian Aborigine population. For this reason I am directly involved with an Antigenicity and Immunogenicity project examining the immunogenicity of HLA epitopes in solid organ transplant recipients.
Australia, and the wider Asia-Pacific Histocompatibility and Immunogenetics Association (APHIA), have always had a significant role to play in the HLA community. The unique ethnic background of many of our populations is critical information to study the immunogenicity of HLA mismatches, to validate T and B cell epitopes and to determine acceptable mismatches in the transplant setting. It will therefore be my position to strongly encourage Australian and indeed all Asia-Pacific laboratories to contribute and participate in the upcoming IHIWS.

Read more

for more information on the
18th International HLA & Immunogenetics Workshop
please visit our website.

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