Elevated proinflammatory cytokines in patients suffering from Aicardi-Goutières syndrome

Written on Friday 9 May 2014

Aicardi-Goutières syndrome, or AGS, is a hereditary genetic disease characterised by brain calcification, brain white matter involvement and increase of interferon alpha, a protein belonging to the family of cytokines which are implicated in the defense against pathogens in our body.
In order to identify the most predictive cytokines of AGS, the expression of a wide panel of these proteins was explored in the plasma and the cerebrospinal fluid (CSF) from AGS patients of different ages. The plasma of 22 AGS patients with known mutations were compared to those of 8 age-matched normal controls. In parallel, a dosage of cytokines in the CSF of 33 patients, including the 22 patients previously tested, was carried out using the same method.
A significant elevation of certain cytokines such as FMS-like Tyrosine Kinase 3 Ligand (Flt3L), IP-10, interleukin (IL)-12p40, Il-15, the tumor necrosis factor alpha (TNF alpha) and soluble IL-2 receptor alpha is observed both in the plasma and in the CSF of AGS patients.
The level of most cytokines drops exponentially with age. However, certain cytokines such as IP-10 remain at a high level beyond the age of the young infant.
In conclusion, patients suffering from AGS show a high level of pro-inflammatory cytokines in the plasma and in the CSF. Certain of these cytokines remain elevated beyond the initial phase of the disease and may represent excellent diagnostic and therapeutic markers of the illness. They could also allow a better understanding of the disease.

Disease: Aicardi-Goutières Syndrome
Subjects: 22 patients and 8 healthy subjects
Type of study: Pathophysiology
Laboratory: Dr. Adeline Vanderver, Center for Genetic Medicine Research, Department of Neurology, Children’s National Medical Center, Washington D.C., USA
Funding: ELA

Source : A. Takanohashi, M. Prust, J. Wang, H. Gordish-Dressman, M. Bloom, G.I. Rice, J.L. Schmidt, Y.J. Crow, P. Lebon, T.W. Kuijpers, K. Nagaraju, A. Vanderver. Elevation of proinflammatory cytokines in patients with Aicardi-Goutières syndrome. Neurology 2013, 80(11):997-1002.

Scientific information provided in collaboration with the INIST-CNRS Institute, Institute for Scientific and Technical Information