The Immunopathology of Rasmussen's Syndrome: Chemokines and Chemokine-Receptors Responses.
Abstract number :
C.01
Submission category :
Year :
2000
Submission ID :
3335
Source :
www.aesnet.org
Presentation date :
12/2/2000 12:00:00 AM
Published date :
Dec 1, 2000, 06:00 AM
Authors :
Carlos A Pardo, David Irani, Eileen P Vining, Freeman M John, Johns Hopkins Univ Sch of Medicine, Baltimore, MD; Johns Hopkins Sch of Medicine, Baltimore, MD.
RATIONALE: Rasmussen's syndrome (RS) is a chronic progressive inflammatory encephalopathy believed to be immunologically mediated. While some investigators suggest the presence of a humoral mediated injury, our studies indicate that neuronal injury in RS is mediated by T-cell and microglial responses. To study immunopathological factors in RS, we evaluated the profile of selected chemokines and their receptors in patients with RS. METHODS: The expression of macrophage chemoattractant protein 1 (MCP-1), fractalkine, and interferon inducible protein (IP-10) and their receptors, was studied by immunocytochemistry in brain areas with different stages of disease from ten RS patients. Tissues from non-RS epilepsy patients (n=5) were used as controls. In three RS patients , additional flow cytometric analysis of brain lymphocytes was performed. RESULTS: The expression of MCP-1, fractalkine and IP-10 was increased in areas with early and intermediate stages of cortical damage in RS . MCP-1 and fractalkine were found in reactive astrocytes while IP-10 was conspicuously present in a perineuronal net around subsets of neurons undergoing lymphocytic injury. Subsets of neurons had marked immunoreactivity for fractalkine. CCR2, the receptor for MCP-1, was found in brain lymphocytes in RS patients and flow cytometric analysis showed an increased population of CCR2+ T-cells in lymphocytes isolated from brain tissue as compared with blood lymphocytes. In contrast, activated microglial cells and reactive astrocytes expressed CX3CR1, the receptor for fractalkine. CONCLUSIONS: Chemokines and chemokine-receptors are involved in the mechanisms of neuronal-glial reactions and lymphocyte recruitment that lead to neuronal injury in RS. The presence of CCR2+ in brain lymphocytes suggests an active process of recruitment /activation of lymphocytes mediated by MCP-1, while fractalkine and IP-10 and their receptors appear to be involved in neuronal-glial interactions. These findings support the hypothesis of the role of T-cell and microglial mediated injury in RS and can contribute to the design of new immunotherapies that modify lymphocyte responses in RS.