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Using genes to triangulate the pathophysiology of granulomatous autoinflammatory disease: NOD2, PLCG2 and LACC1.

Abstract

The intersection of granulomatosis and autoinflammatory disease is a rare occurrence that can be generally subdivided into purely granulomatous phenotypes and disease spectra that are inclusive of granulomatous features. NOD2 (nucleotide binding oligomerization domain containing 2)-related disease, which includes Blau syndrome and early onset sarcoidosis, is the prototypic example of granulomatous inflammation in the context of monogenic autoinflammation. Granulomatous inflammation has also been observed in two related autoinflammatory diseases caused by mutations in PLCG2 (phospholipase C gamma 2). More recently, mutations in LACC1 (laccase domain containing 1) have been identified as the cause of a monogenic form of systemic juvenile idiopathic arthritis, which does not itself manifest granulomatous inflammation, but the same LACC1 mutations have also been shown to cause an early onset, familial form of a well-known granulomatous condition, Crohn's disease (CD). Rare genetic variants of PLCG2 have also been shown to cause a monogenic form of CD, and moreover common variants of all three of these genes have been implicated in polygenic forms of CD. Additionally, common variants of NOD2 and LACC1 have been implicated in susceptibility to leprosy, a granulomatous infection. Although no specific mechanistic link exists between these three genes, they form an intriguing web of susceptibility to both monogenic and polygenic autoinflammatory and granulomatous phenotypes.

More information

Type
Journal Article
Author
Szymanski AM
Ombrello MJ
Year of Publication
2018
Journal
International immunology
Language
eng
ISSN Number
1460-2377
DOI
10.1093/intimm/dxy021
Alternate Journal
Int. Immunol.
Publication Language
eng

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