Elevated Serum Ferritin Is Associated with Reduced Survival in Amyotrophic Lateral Sclerosis

<div><h3>Background</h3><p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder caused by the loss of motor neurons. Its etiology remains unknown, but several hypothesis have been raised to explain motor neuron death, including oxidative stress. Dysregulation of cellular iron metabolism can lead to increased oxidative stress, and existing data argue for a role of iron metabolism in ALS pathophysiology.</p> <h3>Methods</h3><p>We performed a retrospective analysis of iron metabolism (IM) variables (serum levels of iron, transferrin, ferritin, and TSC for Transferrin Saturation Coefficient) in a cohort of 694 ALS patients and 297 healthy controls.</p> <h3>Results</h3><p>Serum ferritin levels and TSC were higher, whereas serum transferrin levels were lower in ALS patients than controls. In addition, patients with a high level serum ferritin had a shorter survival time compared to those with low level serum ferritin (618 days versus 921 days for men subgroup; p = .007). Site of onset and ALS-FRS score were not associated with IM variables.</p> <h3>Conclusion</h3><p>This study suggests that ALS patients may have increased iron storage, as measured by increased serum ferritin and TSC. Elevated serum ferritin may also have a deleterious impact on survival in ALS.</p> </div

Survival times in ALS patients according to gender and IM variables tertiles (low, medium and high levels) (means with standard deviations, in days).

<p>For each tertile group, mean age is indicated below survival time mean value.</p

ALS-FRS scores in ALS patients according to gender and IM variables tertiles (low, medium and high levels) (means with standard deviations).

<p>For each tertile group, mean age is indicated below ALS-FRS mean value.</p

Serum ferritin levels for women according to age (< or > to 45 years old) and disease status (means with standard deviations).

<p>Serum ferritin levels for women according to age (< or > to 45 years old) and disease status (means with standard deviations).</p

IM variables levels in ALS patients according to site of onset (means with standard deviations).

<p>p values are adjusted for sex for serum iron, serum transferrin and TSC, and for sex and age for serum ferritin.</p

General characteristics of healthy controls and ALS populations.

<p>Three slightly different ALS populations are shown here. Among 694 ALS patients with a serum iron value available, serum transferrin values and serum ferritin values were available for 677 and 629 patients, respectively.</p

Global strategy of the analysis illustrating the times of sample collection, the parameters collected and the three main objectives of the study.

<p>Global strategy of the analysis illustrating the times of sample collection, the parameters collected and the three main objectives of the study.</p

Venn diagram showing the 15 most discriminating metabolites in PLS-DA models which are associated with disease evolution (variation of ALSFRS-r, BMI, MMT, SVC over 1 year) in patients in Group O.

<p>Venn diagram showing the 15 most discriminating metabolites in PLS-DA models which are associated with disease evolution (variation of ALSFRS-r, BMI, MMT, SVC over 1 year) in patients in Group O.</p

Venn diagram representing the 15 best discriminating metabolites between patients in Group P and patients in Group O at V1, V12 and over one year (V12-V1) in OPLS-DA models built from blood metabolomic profiles.

<p>Venn diagram representing the 15 best discriminating metabolites between patients in Group P and patients in Group O at V1, V12 and over one year (V12-V1) in OPLS-DA models built from blood metabolomic profiles.</p

Characteristics of patients at baseline (one month after the randomisation visit).

<p>Data from the entire cohort [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198116#pone.0198116.ref006" target="_blank">6</a>] are provided to confirm the representativeness of the population selected for the present study. Probability values correspond to the comparisons between Group O and Group P in this present study.</p