Studies in humans with PID have been complementary. For example, human studies have highlighted that:
- Defects in more than one gene can give rise to a similar primary immunodeficiency syndrome
- The same genetic mutation can give rise to a variable phenotype, depending on the modulating effect of genetic and environtmental influences
- Defects in components of innate and adaptive immunity that are required for homeostasis of the immune response may result in autoimmunity or autoinflammatory syndromes rather than increased susceptibility to infection, thus extending the clinical spectrum of “primary immunodeficiency diseases”.