Series Editors:
Dr Cindy Ma, Garvan Institute of Medical Research, Sydney, Australia
Professor Stuart Tangye, Garvan Institute of Medical Research, Sydney, Australia
We are delighted to present latest our review series, ‘Inborn errors of Immunity: The Goldilocks effect – susceptibility to disease due to a little too much or a little too little’ led by Clinical and Experimental Immunology Section Editor Dr Cindy Ma and Professor Stuart Tangye, Garvan Institute of Medical Research, Sydney, Australia.
Inborn errors of immunity (IEI) are caused by germline variants in single genes that affect the development and/or function of immune cells, which can lead to increased susceptibility to severe and recurrent infection. However, the spectrum of individual IEIs is very broad, and extends beyond infectious diseases to include autoimmunity, autoinflammation, malignancy and atopic disease.
IEIs offer a unique opportunity to study the direct links between genetic defects and immune dysregulation, demonstrating the impact of individual genes on immune function. Thus, IEI have defined the roles of genes, molecules, signalling pathways and cell types in host defence and immune regulation, and have formed the basis of better therapies for immunopathologies.
The advent and application of next generation sequencing has expedited the identification of genetic causes underlying IEI. To date, the genetic cause of >485 IEI has been described and it has become increasingly clear that pathogenic variants can cause disease via different forms of inheritance, resulting in loss-of-function (LOF), gain-of function (GOF), dominant negative (DN) function or haploinsufficiency (HI) of the encoded protein.
In this review series, our guest editors highlight new insights into IEI due to variants in genes that result in both LOF or GOF of the encoded protein and the arising clinical disease outcomes.
Articles in the series
Editorial
Inborn errors of immunity: the Goldilocks effect—susceptibility to disease due to a little too much or a little too little
Cindy S Ma and Stuart G Tangye
Reviews
The yin and the yang of early classical pathway complement disorders
Kathleen E Sullivan
Inborn errors of immunity with loss- and gain-of-function germline mutations in STAT1
Takaki Asano, Takanori Utsumi, Reiko Kagawa, Shuhei Karakawa, Satoshi Okada
The ups and downs of STAT3 function: too much, too little and human immune dysregulation
Joseph Mackie, Cindy S Ma, Stuart G Tangye, Antoine Guerin
Inborn errors of human IKAROS: LOF and GOF variants associated with primary immunodeficiency
Hye Sun Kuehn, Brigette Boast, Sergio D Rosenzweig
Mistuned NF-κB signaling in lymphocytes: lessons from relevant inborn errors of immunity
Gina Dabbah-Krancher, Andrew L Snow