STING-associated vasculopathy with onset in infancy

STING-associated vasculopathy with onset in infancy
Autosomal dominant pattern is the inheritance manner of this condition
Specialty	Medical genetics
Causes	Mutations in the TMEM173 gene

STING-associated vasculopathy with onset in infancy (SAVI^[1]) is a rare autoinflammatory vasculopathy associated with the stimulator of interferon genes (STING) protein and characterised by severe skin lesions and interstitial lung disease.

Signs and symptoms[]

The onset is in infancy. The skin lesions occur on cheeks, nose, fingers, toes and soles.^[2] They may vary in appearance but frequently develop into non-healing ulcers. Interstitial lung disease is also common. Some individuals may not experience any obvious skin issues. All affected children fail to thrive.^{[citation needed]}

Other features include myositis and joint stiffness. Some children experience hyper mobility, and joint pain.^{[citation needed]}

Imaging:

Chest X rays show sign consistent with interstitial lung disease.^{[citation needed]}

Bloods:

Anemia, leukopenia, thrombocytosis, T cell lymphopenia with normal B cells and hypergammaglobulinemia may occur.^{[citation needed]}

Autoantibodies may be present including antinuclear, antiphospholipid, and anticardiolipin antibodies.^{[citation needed]}

The erythrocyte sedimentation rate and C reactive protein levels tend to be raised.^{[citation needed]}

Biopsies:

Skin biopsies show inflammation of the capillaries and microthrombosis. Immunoglobulin M and C3 deposition may be present.^{[citation needed]}

Lung biopsies show alveolitis, follicular hyperplasia, B-cell germinal centers and interstitial fibrosis. Some children demonstrate pulmonary alveolar protianosis on Lavage.^{[citation needed]}

Genetics[]

This condition is due to mutations in the TMEM173 gene. This gene is located on the long arm of chromosome 5 (5q31.2) and encodes the stimulator of interferon genes (STING) protein. There are 3 disease causing mutations in the dimerization domain of STING that cause SAVI; V155M, N154S, and V147L.^{[citation needed]}

Pathopysiology[]

This only partly understood. The wild type protein (STING) is normally found in the cytoplasm of the cell. The mutant forms are located in the Golgi apparatus.^{[citation needed]}

Diagnosis[]

The condition may be suspected on clinical grounds. The diagnosis is made by sequencing the TMEM173 gene.^{[citation needed]}

Treatment[]

No specific treatment is known. Management is supportive. Research into the efficacy of a subgroup of medications known as JAK inhibitors is underway.^{[citation needed]}

Epidemiology[]

This condition is considered rare, with 9 cases reported in the literature up to 2019.^{[citation needed]}

Research[]

This condition was first described in 2014.^[3] In 2017 a group led by Dr. Jonathan Miner at Washington University in St. Louis created a mouse model of SAVI. Dr. Miner's research team used CRISPR-CAS9 genome editing to introduce a mutation into the mouse STING gene (TMEM173)^[4] that was analogous to a human SAVI-associated mutation. These mice, known as STING N153S mice, developed spontaneous lung disease and a severe immunodeficiency to a herpesviruses.^[5]

References[]