From idiopathic infectious diseases to novel primary immunodeficiencies.

Primary immunodeficiencies are typically seen as rare monogenic conditions associated with detectable immunologic abnormalities, resulting in a broad susceptibility to multiple and recurrent infections caused by weakly pathogenic and more virulent microorganisms. By opposition to these conventional primary immunodeficiencies, we describe nonconventional primary immunodeficiencies as Mendelian conditions manifesting in otherwise healthy patients as a narrow susceptibility to infections, recurrent or otherwise, caused by weakly pathogenic or more virulent microbes. Conventional primary immunodeficiencies are suspected on the basis of a rare, striking, clinical phenotype and are defined on the basis of an overt immunologic phenotype, often leading to identification of the disease-causing gene.