Hans. D. Ochs
Dept. of Pediatrics, University of Washington, USA
The low infant mortality achieved in developed countries has allowed the identification of patients with unusual bacterial, fungal and viral infections that are caused by primary defects of the immune system. During the past 50 years, many characteristic clinical phenotypes of primary immunodeficiencies (PID) have been delineated; more recently, the genetic basis for over 100 PIDs have been established. These molecularly defined defects involve all aspects of the intricate defense system that is composed of T and B cells, Phagocytic cells and Complement. Functionally, we can differentiate PIDs that involve surface receptors (e.g. CD40 ligand/CD40, common gamma chain); soluble factors (IL-12); cytoplasmic signaling molecules (e.g. Btk, ZAP70); antigen peptide recognition molecules (e.g. MHC-I, II); defective DNA recombination/splicing molecules (Rag1/2, ATM, Arthemis); defective lymphocyte apoptosis (Fas, Caspases); DNA binding proteins (FoxP3); defective purine metabolism (ADA, PNP); adhesion molecule deficiencies (CD18); Natural Killer Cell defects (SAP); and NADPH oxydase deficiencies (CGD).
The study of PID has improved our understanding of the function of the immune system components, has provided tools to confirm the diagnosis on the molecular level, detect carriers and perform prenatal diagnosis; and to develop the first gene therapy protocols. Thus, the understanding of PID has assumed an important place in modern Pediatrics, both in developed as well as in emerging developed countries.