Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival.
Bottom Line: The mRNA levels of FoxP3, TGF-β, IL4 and Gata3, a Th2 transcription factor, were reduced in rapidly progressing patients and inversely correlated with progression rates.No differences in IL10, Tbx21, a Th1 transcription factor or IFN-γ expression were found between slow and rapidly progressing patients.Importantly, early reduced FoxP3 levels could be used to identify rapidly progressing patients.
Affiliation: Department of Neurology, The Methodist Hospital Research Institute, Houston, TX, USA. email@example.comShow MeSH
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Mentions: We evaluated whether low FoxP3 mRNA levels expressed in leukocytes early in disease were predictive of a worse outcome. As shown by Kaplan–Meier curves indicating percent survival of ALS patients to 100 AALS points over time, 66% of patients with FoxP3 levels below the ROC cutoff were above 100 AALS points at the end of the 3.5 years, while only 36.7% of patients with FoxP3 levels above the ROC cutoff were above 100 AALS points (p = 0.0072; Fig 9A). In addition, the numbers of deceased ALS patients or patients placed on a ventilator during the 3.5-year evaluation period were compared between patients expressing high versus low FoxP3 levels, as shown by Kaplan–Meier curves. The survival data indicate that 35% of patients with FoxP3 levels below the ROC analysis cutoff were placed on a ventilator or were deceased at the end of the 3.5 years, while only 13% of patients with FoxP3 levels above the cutoff were on a ventilator or deceased (p = 0.013; Fig 9B). The survival data was also analyzed by the Chi square test, which again revealed that approximately three times more ALS patients with low FoxP3 mRNA levels were placed on a ventilator or were deceased at the end of the 3.5 years compared with ALS patients with high FoxP3 mRNA levels (p = 0.023; Fig 9C).
Affiliation: Department of Neurology, The Methodist Hospital Research Institute, Houston, TX, USA. firstname.lastname@example.org