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Review
. 2019 Dec 6;2019(1):443-448.
doi: 10.1182/hematology.2019000051.

Primary immunodeficiencies: novel genes and unusual presentations

Luigi D Notarangelo  1 , Gulbu Uzel  1 , V Koneti Rao  1
Affiliations
Review

Primary immunodeficiencies: novel genes and unusual presentations

Luigi D Notarangelo et al. Hematology Am Soc Hematol Educ Program. .

Abstract

Recent advances in genomics have greatly expanded the spectrum of primary immune deficiencies (PIDs). Along with the identification of pathogenic variants in novel genes, distinct phenotypes have been associated with different variants in the same gene. Although PIDs have been historically defined based on increased susceptibility to infections, immune dysregulation has emerged as a frequent and in some cases, predominant phenotype. Autoimmune cytopenias with onset in childhood, lasting longer than 12 months, and affecting multiple lineages should raise the suspicion of a possible PID with monogenic origin. Characterization of the various molecular and cellular mechanisms responsible for these unusual manifestations of PIDs, although at times resource intensive, may allow for targeted intervention in many of them.

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Conflict of interest statement

Conflict-of-interest disclosure: G.U. is the principal investigator for trial NCT03733067, and the National Institutes of Health Clinical Center participates in trial NCT02859727. L.D.N. and V.K.R. declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Distribution of gene defects included in the last International Union of Immunological Societies (IUIS) Classification of PIDs (1) and causing diseases manifesting predominantly with infections, immune dysregulation, or both: a personal view.
Figure 2.
Figure 2.
Schematic diagram of a practical approach to the management of cytopenias in immune dysregulatory disorders. APDS, activated phosphatidylinositol 3-kinase δ syndrome; CBC, complete blood count; DAT, direct antiglobulin test; GOF, gain-of-function; IgG, immunoglobulin G; IV, intravenous; MMF, mycophenolate mofetil; NK, natural killer; PASLI, p110 delta-activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency; PIK3CD, phosphatidylnositol 3-kinase C delta.
See this image and copyright information in PMC

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