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Journal of Autoimmunity
Volume 35, Issue 3, November 2010, Pages 199-205
Special Issue - In Honour of Professor Haralampos M. Moutsopoulos
The odd couple: A fresh look at autoimmunity and immunodeficiency
Ian R. Mackaya, , , Natasha V. Leskovsekb and Noel R. Rosec, d,
a Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia
b Cooley LLP, Washington DC 20006, USA
c Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA
d Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, MD 21205, USA
Available online 6 September 2010.
Abstract
The paradoxical relationship between immunodeficiency (under-responsiveness) and autoimmunity (over-responsiveness) affecting the immune system was debated at the Fourth AARDA Colloquium on cross-disciplinary issues in autoimmunity. Immunodeficiency disease and autoimmune disease, far from being mutually exclusive, share profound dysregulation of the immune system. Among the most keenly discussed issues were: i) the remarkably high number of molecularly identified primary immunodeficiencies with autoimmune expressions; ii) the homeostasis of immune function such that deficiency in any one given compartment can result in over activity in the same or another compartment; iii) whilst some immune deficiency states are essentially monogenic, each of them can exhibit striking variability in autoimmune outcome, indicative of epigenetic or environmental influences on phenotypic expression; iv) innate immunity, particularly complement defects, as well as adaptive immunity, is complicit in the immunodeficiency-autoimmunity axis; v) features of certain of the disorders discussed at the meeting forced a reappraisal of what actually is meant by ‘autoimmune disease’. It was concluded that genes that determine inherited immunodeficiencies, hitherto rather neglected by autoimmunologists, compel attention to consideration of molecular genetic anomalies critical for emergence of autoimmune disease in humans and animals.