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. firstname.lastname@example.orgShow MeSH
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Mentions: CD4+CD25High Tregs were evaluated to determine whether they are associated with disease progression in ALS patients, as in mSOD1 mice. Single blood samples from 54 ALS patients from all stages of disease and control volunteers were examined by flow cytometry (Fig 1A). The percentages of CD3+, CD4+ or CD8+ lymphocytes (data not shown), or CD4+CD25High Tregs (Fig 1B) of total leukocytes from ALS patients and controls were not different. However, differences were noted when the patients were separated and grouped based on their rate of disease progression at the time of blood collection [rate was determined as the change in AALS score, change in time (months), comparing the initial clinical evaluation with the evaluation performed at the time of blood collection]. Patients were grouped into slowly (<1.5 AALS points/month, 28 patients) versus rapidly (≥1.5 AALS points/month, 26 patients) progressing patients using the Appel ALS (AALS) score (Fig 1C; Haverkamp et al, 1995), as this rate separated the patients surviving only a year or two after diagnosis from those that survive up to 6 years or more after diagnosis and also divided these patients approximately in half. Leukocytes from blood of rapidly progressing patients consisted of 31% fewer CD4+CD25High Tregs compared with slowly progressing patients (p = 0.018) and 32% fewer CD4+CD25High Tregs compared with controls (p = 0.003). CD4+CD25High Tregs from slowly progressing patients were not different than controls (p = 0.846). No correlation with age (p = 0.689) nor difference between limb versus bulbar onsets (p = 0.684) were found. The percent of CD4+CD25High Tregs in ALS patients were inversely correlated with rate of disease progression; the greater the number of Tregs, the slower the disease progression rate (p = 0.028; Fig 1D). These results indicate an association between numbers of CD4+CD25High Tregs in blood with the rate at which disease progresses in ALS patients.
Affiliation: Department of Neurology, The Methodist Hospital Research Institute, Houston, TX, USA. email@example.com