A&R: The enhancement of interferon gene stimulating factor induces the production of type I interferon in COPA syndrome

Oatomer subunit alpha (COPA) syndrome, also known as autoinflammatory interstitial lung, joint, and kidney disease, is caused by heterozygous mutations in COPA .
The study found a new variant of COPA in 4 patients in a family .
By studying these 4 patients and analyzing the results of the gene-targeted mouse model, we can clarify whether and how the mutation causes the symptoms of COPA syndrome .

Oatomer subunit alpha (COPA) syndrome, also known as autoinflammatory interstitial lung, joint, and kidney disease, is caused by heterozygous mutations in COPA COPA .

The study found a new variant of COPA in 4 patients in a family .
By studying these 4 patients and analyzing the results of the gene-targeted mouse model, we can clarify whether and how the mutation causes the symptoms of COPA syndrome .

 

The study .

7 family members were all the exons of genomic sequencing peripheral blood mononuclear cells , and using RT-qPCR measured in peripheral blood cells of the I interferon (IFN) relevant mRNA expression (including ISG15 , IFIT1 , IFI44L , SIGLEC1 , IFI27 and RSAD2 )

The study .
7 family members were all the exons of genomic sequencing peripheral blood mononuclear cells , and using RT-qPCR measured in peripheral blood cells of the I interferon (IFN) relevant mRNA expression (including ISG15 ISG15 , , IFIT1 IFIT1 , , IFI44L IFI44L , , of a SIGLECl of a SIGLECl , , IFI27 IFI27 and RSAD2 RSAD2 )

Researchers identified heterozygous mutations in COPA COPA ( c.
725T>G , p.
Val242Gly ) in 4 affected family members .
Family members with this mutation have higher IFN scores .
In vitro analysis showed that COPA COPA V242G and previously reported pathogenic mutations enhanced the type I IFN promoter activity induced by stimulus of interferon gene (STING) .
Copa Copa ^V242G/+ V242G/+ mice exhibited interstitial lung disease and STING -dependent interferon-stimulated gene expression .

V242G is a new type of COPA COPA mutation found in 4 patients in one family .
Interstitial lung disease appeared in gene-targeted mice with the V242G mutation, and the response of the STING pathway was enhanced, leading to an increase in type I IFN production .
By focusing on the activation of the STING pathway, a new treatment strategy for COPA syndrome was introduced .
By focusing on the activation of the STING pathway, a new treatment strategy for COPA syndrome was introduced .
 

Original source:

Original source:

Kato, T.

, Yamamoto, M.
, Honda, Y.
, Orimo, T.
(2021), Augmentation of Stimulator of Interferon Genes--Induced Type I Interferon Production in COPA Syndrome.
Arthritis Rheumatol, 73: 2105-2115.

Kato, T.

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