ABSTRACT
Human primary immunodeficiencies (PIDs) are often thought to be confined to a few rare, familial, monogenic, recessive traits impairing the development or function of one or several leucocyte subsets and resulting in multiple, recurrent, opportunistic and fatal infections in infancy. We highlight here the rapidly growing number of exceptions to each of these conventional qualifications. Indeed, bona fide PIDs include common and sporadic illnesses and may present as dominant, or even polygenic traits; their pathogenesis may involve non haematopoietic cells, and they may result in single episode of illness, with a single or multiple morbid phenotypes, some of which may involve infection, in otherwise healthy adults. We need to increase awareness of the multitude of clinical presentations of human PIDs considerably and rapidly in the medical community. Human PIDs should be considered in a wide range of clinical situations.
Subject(s)
Immunologic Deficiency Syndromes/genetics , Adult , Child , Common Variable Immunodeficiency/epidemiology , Common Variable Immunodeficiency/genetics , Crohn Disease/genetics , Encephalitis, Herpes Simplex/genetics , Epidermodysplasia Verruciformis/genetics , Female , Genetic Predisposition to Disease , Genotype , Humans , Immunologic Deficiency Syndromes/epidemiology , Interleukin-1 Receptor-Associated Kinases/deficiency , Interleukin-1 Receptor-Associated Kinases/genetics , Leprosy/genetics , Male , Phenotype , Receptors, Interferon/deficiency , Receptors, Interferon/genetics , Receptors, Interleukin-12/deficiency , Receptors, Interleukin-12/genetics , fas Receptor/genetics , Interferon gamma ReceptorABSTRACT
The molecular aetiology of familial susceptibility to disseminated mycobacterial disease, usually involving weakly pathogenic strains of mycobacteria, has now been elucidated in more than 30 families. Mutations have been identified in five genes in the interleukin-12-dependent interferon-gamma pathway, highlighting the importance of this pathway in human mycobacterial immunity. Knowledge derived from the study of these rare patients contributes to our understanding of the immune response to common mycobacterial pathogens such as Mycobacterium tuberculosis and Mycobacterium leprae, which remain major public health problems globally. This knowledge can be applied to the rational development of novel therapies and vaccines for these important mycobacterial diseases.