T Cell Phenotypes in Amyotropic Lateral Sclerosis (ALS), Influence of Vitamin D
T Cell Phenotypes in Amyotropic Lateral Sclerosis (ALS), Influence of Vitamin D
ALS is a devastative disorder characterized by motor neuron degeneration. Median survival is
 3 years after onset, but may vary from a few months to more than 30 years. Various factors
 have been suspected to play a role in such a variation, but recently, it has been described
 that regulatory T-lymphocytes (T regs) may mediate ALS progression and survival. Vitamin D is
 an hormone know to regulated T reg function in vivo and in vitro. It have recently
 demonstrated that vitamin D (VD) levels correlated with ALS prognosis. The investigator want
 to go further in the study of the immune processes that could modulate prognosis in ALS. This
 could allow proposing VD as a potential treatment of ALS in a future trial. More largely,
 this could reinforce arguments in favor of an immune intervention to attenuate the severity
 of this devastating disorder.
ALS is a devastative disorder characterized by motor neuron degeneration. Median survival is
 3 years after onset, but may vary from a few months to more than 30 years. Various factors
 have been suspected to play a role in such a variation, but recently, it has been described
 that regulatory T-lymphocytes (T regs) may mediate ALS progression and survival. Vitamin D is
 an hormone know to regulated T reg function in vivo and in vitro. It have recently
 demonstrated that vitamin D (VD) levels correlated with ALS prognosis and patients with a
 severe VD deficiency had a 6 time more rapid evolution than those with normal VD levels. The
 investigator want to go further in the study of the immune processes that could modulate
 prognosis in ALS. We propose 1- to study T cell phenotypes (Treg, CD4 (cluster of
 differentiation 4) -Th1, -Th17, -Th2, CD8 (cluster of differentiation 8)and NK) in ALS vs
 controls ; 2- In VD-deficient patients, to analyze the influence of a vitamin D
 supplementation on T cell phenotypes ; 3- to study the relationships between T cell
 phenotypes and ALS prognostic factors. The project will include 70 ALS patients and 27
 controls in this prospective study. VD-deficient patients will be supplemented, according to
 national recommendations for 6 months, and the evolution of T cell phenotypes will be
 followed over 1 year. We hope to demonstrate first that T cell phenotypes in ALS are
 consistent with a pro inflammatory profile, compared to controls, secondly that VD treatment
 modulates T cell phenotypes towards a non-inflammatory one and, thirdly, that inflammatory T
 cell phenotypes correlate with a worse prognosis of the disease. This could allow proposing
 VD as a potential treatment of ALS in a future trial. More largely, this could reinforce
 arguments in favor of an immune intervention to attenuate the severity of this devastating
 disorder.
For the patients :

 Inclusion Criteria:

 -  Man or woman with sporadic ALS and a possible, probable or definite diagnosis
 regarding the revised Escorial criteria (Forbes et al., 2001). Patients are followed
 quarterly according to national recommendations. At the end of the follow up period (1
 year for each patient), all patients remaining in the " possible " group of diagnosis
 will be excluded.

 -  Disease onset (date of onset of muscle weakness) < 18 months at the time of inclusion.

 -  Age: 30 to 80 years-old, inclusive.

 -  Patient treated by riluzole at a steady dosage since at least 3 months.

 -  Patient accepting to give informed consent

 Exclusion criteria will be :

 -  A previous treatment with VD in the preceding 2 years, whatever the dose used.

 -  Patient with an already known autoimmune disorder

 -  Patient with severe ALS involvement suggesting that survival over the 1 year follow up
 is highly unlikely (ex : tetraplegia, use of non-invasive ventilation for more than 10
 hrs/day, ALSFRS-R (ALS Functional Rating Scale) score < à 20).

 -  Pregnant or breast-feeding woman.

 -  Patient without social security insurance

 For the Controls:

 Controls will be spouses of our ALS patients. Such a group has the advantage of similar
 life style conditions, and frequently similar geographical origin. Controls and ALS
 patients will match for age and gender. Controls will also fulfill the following inclusion
 and exclusion criteria

 Inclusion criteria

 •Subject accepting to give informed consent

 Exclusion criteria

 -  Subject with an already known neurodegenerative disorder

 -  Subject with an already known autoimmune disorder

 -  Subject who received a treatment with VD in the preceding 2 years, whatever the dose
 used.

 -  Pregnant or breastfeeding woman

 -  Subject without social security insurance