CIRCA team

Researchers at the Garvan lead the Clinical Immunogenomics Research Consortium Australasia (CIRCA) which is dedicated to investigating the genetics involved in rare diseases involving the immune system. CIRCA researchers from the Garvan include the Immunology and Immunodeficiency, Immunogenomics, Intravital Microscopy and  B Cell Biology labs, as well as genome informatics experts. Understanding the genes and mutations behind immune diseases will help improve future treatments that can specifically target these mutations.

AR-HEIS is a genetic immune disease where IgE levels in the body are highly elevated with most patients showing a dedicator of cytokinesis 8 (DOCK8) deficiency. Individuals with AR-HEIS are often susceptible to allergic conditions such as asthma and severe food and environmental allergies, as well as skin infections, recurrent pneumonia and increased risk of cancer. A bone marrow transplant, or haematopoietic stem cell transplant (HSCT), has recently been seen as a cure for AR-HEIS but it does not address all underlying issues; for example, many studies have shown that allergies may only slightly improve or not improve at all after HSCT. Research is being done in this area to investigate why the genetic mutations in AR-HEIS have an effect on allergies, even after HSCT.

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Key areas of investigation

Immune response pathways affected by DOCK8 deficiency

DOCK8 deficiency is the most common genetic mutation found in patients with AR-HEIS. DOCK8 deficiency causes a combined immunodeficiencies characterised by skin and pulmonary infections (viral, bacterial and fungal), severe eczema, increased risk of cancer, increased IgE levels and allergies. If left untreated, the median survival for those with a DOCK8 deficiency is only 10-20 years.  HSCT is seen as a cure for AR-HEIS with ~80% survival rate after the transplant, however it may not resolve or even improve allergic disease. 

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Other genetic mutations causing AR-HEIS

Our CIRCA researchers in collaboration with many international institutes were the first to describe a different mutation that caused AR-HEIS. They were able to characterise the previously unknown gene ZNF341 and studied the effects of ZNF341 mutations on various immune cells. Through this, they were able to determine which immune pathways were affected by ZNF341 mutations, and associated a particular pathway to increased inflammatory allergic reactions. The discovery and characterisation of genetic mutations that affect immune response is an important step towards understanding immune diseases and how to improve treatments.

National and international collaborations

  • Australian National University, Canberra, Australia
  • Baylor College of Medicine, Houston, United Stated of America
  • Boston Children’s Hospital, Boston, United States of America
  • Children’s Hospital at Westmead, Sydney, Australia
  • Great North Children's Hospital, Newcastle upon Tyne, United Kingdom
  • Harvard Medical School, Boston, United States of America
  • Howard Hughes Medical Institute, New York, United States of America
  • Institut Imagine, Paris, France
  • Institut Pasteur, Paris, France
  • Istanbul University, Istanbul, Turkey
  • John Curtin School of Medical Research, Canberra, Australia
  • John Hunter Hospital, New Lambton, Australia
  • Lady Cilento Children’s Hospital, Brisbane, Australia
  • Marmara University, Istanbul, Turkey
  • National Institute of Pediatrics, Mexico City, Mexico
  • National Institutes of Health, Bethesda, United States of America
  • National Institute of Health and Medical Research, Paris, France
  • Necker–Enfants Malades Hospital, Paris, France
  • Necmettin Erbakan University, Konya, Turkey
  • Newcastle upon Tyne University, Newcastle upon Tyne, United Kingdom
  • Queensland Children’s Hospital, Brisbane, Australia
  • Rockefeller University, New York, United States of America
  • Royal Children’s Hospital, Melbourne, Australia
  • Sidra Medicine, Doha, Qatar
  • St Vincent’s Clinical School, Sydney, Australia
  • Sydney Children’s Hospital, Sydney, Australia
  • Tehran University of Medical Sciences, Tehran, Iran
  • Texas Children’s Hospital, Houston, United States of America
  • Universal Scientific Education and Research Network, Tehran, Iran
  • Université d'Angers, Angers, France
  • Université Hassan II, Casablanca, Morocco
  • Université Paris Descartes, Paris, France
  • Université Paris Diderot, Paris, France
  • University of Erlangen-Nürnberg, Erlangen, Germany
  • University of Freiburg, Freiburg, Germany
  • University Hospitals Leuven, Leuven, Belgium
  • University of Queensland, Brisbane, Australia
  • University of Manchester, Manchester, United Kingdom
  • University of New South Wales, Sydney, Australia
  • Women and Children’s Hospital, Adelaide, Australia