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Review
. 2016 Aug 25;128(8):1037-42.
doi: 10.1182/blood-2016-04-712612. Epub 2016 Jul 14.

CHAI and LATAIE: new genetic diseases of CTLA-4 checkpoint insufficiency

Bernice Lo  1 , Jill M Fritz  2 , Helen C Su  3 , Gulbu Uzel  4 , Michael B Jordan  5 , Michael J Lenardo  2
Affiliations
Review

CHAI and LATAIE: new genetic diseases of CTLA-4 checkpoint insufficiency

Bernice Lo et al. Blood. .

Abstract

CTLA-4 is a critical inhibitory "checkpoint" molecule of immune activation. Several recent reports have described patients with immune dysregulation and lymphoproliferative disease resulting from 2 different genetic diseases that directly or indirectly cause CTLA-4 deficiency. Numerous articles have also been published describing CTLA-4 blockade in cancer immunotherapy and its side effects, which are ultimately the consequence of treatment-induced CTLA-4 deficiency. Here, we review these 2 diseases and CTLA-4 blockade therapy, emphasizing the crucial role of CTLA-4 in immune checkpoint regulation.

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Figures

Figure 1
Figure 1
CHAI and LATAIE disease phenotype and mechanism. (A) Clinical features of CHAI and LATAIE disease. (B) Schematic of the CTLA4 exons showing the mutations in CHAI patients. TM, transmembrane domain. A schematic displaying LRBA mutations causing LATAIE can be found in Lo et al, Alkhairy et al, and Gámez-Díaz et al. (C) Model depicting the function of CTLA-4 and its regulation by LRBA.
See this image and copyright information in PMC

References

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