Interferon-γ induced increases in intracellular calcium in T lymphocytes from patients with multiple sclerosis precede clinical exacerbations and detection of active lesions on MRI. Issue 3 (1st September 1997)

• Record Type: Journal Article
• Authors: Martino, G; Filippi, M; Martinelli, V; Brambilla, E; Gobbi, C; Comi, G; Grimaldi, L M E
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 63:Issue 3(1997)
• Page Start: 339
• Page End: 345
• Publication Date: 1997-09-01
• Subjects: multiple sclerosis -- interferon-γ -- lymphocytes -- calcium -- MRI; Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp.63.3.339
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : BACKGROUND: Interferon (IFN)-γ exerts a multiplicity of actions potentially relevant for the pathogenesis of multiple sclerosis, including the expression of a transplasmalemma calcium (Ca 2+ ) influx leading to an intracellular Ca 2+ ([Ca 2+ ]i ) increase able to lower T lymphocyte threshold of excitability. It has been previously shown in a cross sectional cumulative study that this influx is associated with clinical and MRI evidence of disease activity. METHODS: To evaluate the temporal relation between disease activity and the IFN-γ activated Ca 2+ influx in individual patients, a fluorimetric analysis was performed on peripheral blood lymphocytes from eight patients with relapsing-remitting multiple sclerosis every 15 days for one year. Results —Fluctuations of the influx were correlated with clinical events and monthly enhanced brain MRI. The influx was detected a mean of 10.4 (range 7-17) times per patient during our analysis. In 61% of the occasions, influx induced [Ca 2+ ]i increases were recorded in each patient in more than two consecutive measurements, determining sustained [Ca 2+ ]i increases lasting for a mean of 31.5 days. Peak [Ca 2+ ]i increases preceded clinical attacks (P=0.04) or maximal detection of brain MRI enhancing lesions (P=0.05) by a mean of 30.8 and 34.2 days respectively. Spectral analysis of time series further indicated that the fluctuation frequency of [Ca 2+ ]i increases due to the influx over time were superimposable on the appearance of new MRI lesions in all patients and confirmed that in two thirds of the patients these [Ca 2+ ]i increases occurred significantly before (P<0.005) or concurred with new lesion appearance. Finally, the overall presence of the influx throughout the follow up period correlated (P=0.03) with the patients' exacerbation rates. CONCLUSIONS: Intracellular events leading to T lymphocyte activation in multiple sclerosis occur in the peripheral blood before CNS specific events become evident and are, in part, sustained by cytokine induced Ca 2+ mediated phenomena.