Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee

Abstract

We report the updated classification of Inborn Errors of Immunity/Primary Immunodeficiencies, compiled by the International Union of Immunological Societies Expert Committee. This report documents the key clinical and laboratory features of 430 inborn errors of immunity, including 64 gene defects that have either been discovered in the past 2 years since the previous update (published January 2018) or were characterized earlier but have since been confirmed or expanded upon in subsequent studies. The application of next-generation sequencing continues to expedite the rapid identification of novel gene defects, rare or common; broaden the immunological and clinical phenotypes of conditions arising from known gene defects and even known variants; and implement gene-specific therapies. These advances are contributing to greater understanding of the molecular, cellular, and immunological mechanisms of disease, thereby enhancing immunological knowledge while improving the management of patients and their families. This report serves as a valuable resource for the molecular diagnosis of individuals with heritable immunological disorders and also for the scientific dissection of cellular and molecular mechanisms underlying inborn errors of immunity and related human diseases.

Keywords: IUIS; autoinflammatory disorders; immune dysregulation; inborn errors of immunity; next-generation sequencing; primary immune deficiency.

Fig. 1

Rate of discovery of novel inborn errors of immunity: 1983–2019. a The number of genetic defects underlying monogenic immune disorders as reported by the IUIS/WHO committee in the indicated year. b The number of pathogenic gene variants listed in each table by the IUIS committee. Report published in 2017, and the number of new genes for each table contained in this report (red bars). The numbers in each column correspond to the number of genes reported in the 2017 IUIS update (blue bars) [1, 2], the number of new genes for each table contained in this report (red bars), and the total number of genes for each table. Note: only data for Tables 1, 2, 3, 4, 5, 6, 7, and 8 are shown, because Table 9 (bone marrow failure) is a new addition to the current report.