From infectious diseases to primary immunodeficiencies

The field of primary immunodeficiencies has expanded, thanks to the exploration of novel clinical phenotypes and their connection with morbid genotypes, and the subsequent exploration of new patients who have known primary immunodeficiency-defining clinical phenotypes and their connection with novel morbid genotypes. This two-way process is becoming increasingly active, particularly for patients who have infectious diseases in whom the underlying immunologic and genetic causes remain mostly unexplained. The authors review how the exploration of children who have clinical infectious diseases caused by mycobacteria, pneumococcus, and herpes simplex virus recently led to the description of three new groups of primary immunodeficiencies. These three examples justify the continuation of the genetic exploration of novel infectious phenotypes and novel patients who have infections. This challenging process will eventually reap its rewards, to the benefit of patients and their families.