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Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival.

Henkel JS, Beers DR, Wen S, Rivera AL, Toennis KM, Appel JE, Zhao W, Moore DH, Powell SZ, Appel SH - EMBO Mol Med (2012)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The Methodist Hospital Research Institute, Houston, TX, USA. jhenkel@tmhs.org

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Low FoxP3 expression levels are predictive of reduced survivalLeukocytes from 102 patients were collected over a 3-year period during the early stages of disease and evaluated for FoxP3 mRNA expression levels. AALS score was determined every 3 months for 3.5 years.A. Sixty-six percent of patients with FoxP3 expression levels below the cutoff were above 100 AALS points at the end of the 3.5 years, while only 36.7% of the patients with FoxP3 expression levels above the cutoff were above 100 AALS points.B,C. Thirty-five percent of patients with FoxP3 expression levels below the cutoff were placed on a ventilator or were deceased during the 3.5 years, while only 13% of the patients with FoxP3 expression levels above the cutoff were on a ventilator or deceased. Optimum cutoff level was defined by the ROC curve analysis in Fig 7 (FoxP3 = 0.66). *p = 0.013, **p = 0.0072, log-rank tests; #p = 0.023, Chi square test.
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fig09: Low FoxP3 expression levels are predictive of reduced survivalLeukocytes from 102 patients were collected over a 3-year period during the early stages of disease and evaluated for FoxP3 mRNA expression levels. AALS score was determined every 3 months for 3.5 years.A. Sixty-six percent of patients with FoxP3 expression levels below the cutoff were above 100 AALS points at the end of the 3.5 years, while only 36.7% of the patients with FoxP3 expression levels above the cutoff were above 100 AALS points.B,C. Thirty-five percent of patients with FoxP3 expression levels below the cutoff were placed on a ventilator or were deceased during the 3.5 years, while only 13% of the patients with FoxP3 expression levels above the cutoff were on a ventilator or deceased. Optimum cutoff level was defined by the ROC curve analysis in Fig 7 (FoxP3 = 0.66). *p = 0.013, **p = 0.0072, log-rank tests; #p = 0.023, Chi square test.

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).


Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival.

Henkel JS, Beers DR, Wen S, Rivera AL, Toennis KM, Appel JE, Zhao W, Moore DH, Powell SZ, Appel SH - EMBO Mol Med (2012)

Low FoxP3 expression levels are predictive of reduced survivalLeukocytes from 102 patients were collected over a 3-year period during the early stages of disease and evaluated for FoxP3 mRNA expression levels. AALS score was determined every 3 months for 3.5 years.A. Sixty-six percent of patients with FoxP3 expression levels below the cutoff were above 100 AALS points at the end of the 3.5 years, while only 36.7% of the patients with FoxP3 expression levels above the cutoff were above 100 AALS points.B,C. Thirty-five percent of patients with FoxP3 expression levels below the cutoff were placed on a ventilator or were deceased during the 3.5 years, while only 13% of the patients with FoxP3 expression levels above the cutoff were on a ventilator or deceased. Optimum cutoff level was defined by the ROC curve analysis in Fig 7 (FoxP3 = 0.66). *p = 0.013, **p = 0.0072, log-rank tests; #p = 0.023, Chi square test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3569654&req=5

fig09: Low FoxP3 expression levels are predictive of reduced survivalLeukocytes from 102 patients were collected over a 3-year period during the early stages of disease and evaluated for FoxP3 mRNA expression levels. AALS score was determined every 3 months for 3.5 years.A. Sixty-six percent of patients with FoxP3 expression levels below the cutoff were above 100 AALS points at the end of the 3.5 years, while only 36.7% of the patients with FoxP3 expression levels above the cutoff were above 100 AALS points.B,C. Thirty-five percent of patients with FoxP3 expression levels below the cutoff were placed on a ventilator or were deceased during the 3.5 years, while only 13% of the patients with FoxP3 expression levels above the cutoff were on a ventilator or deceased. Optimum cutoff level was defined by the ROC curve analysis in Fig 7 (FoxP3 = 0.66). *p = 0.013, **p = 0.0072, log-rank tests; #p = 0.023, Chi square test.
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).

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The Methodist Hospital Research Institute, Houston, TX, USA. jhenkel@tmhs.org

Show MeSH
Related in: MedlinePlus