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Blood Cell Palmitoleate-Palmitate Ratio Is an Independent Prognostic Factor for Amyotrophic Lateral Sclerosis.

Henriques A, Blasco H, Fleury MC, Corcia P, Echaniz-Laguna A, Robelin L, Rudolf G, Lequeu T, Bergaentzle M, Gachet C, Pradat PF, Marchioni E, Andres CR, Tranchant C, Gonzalez De Aguilar JL, Loeffler JP - PLoS ONE (2015)

Bottom Line: Palmitoleate (16:1) and oleate (18:1) levels, and stearoyl-CoA desaturase indices (16:1/16:0 and 18:1/18:0) significantly increased in blood cells from ALS patients compared to healthy controls.In patients with high 16:1/16:0 ratio, survival at blood collection was extended by 10 months, as compared to patients with low ratio.It therefore deserves further validation in larger cohorts for being used to assess disease outcome and effects of disease-modifying drugs.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U1118, Mécanismes Centraux et Périphériques de la Neurodégénerescence, Strasbourg, France; Université de Strasbourg, UMR_S1118, Fédération de Médecine Translationnelle, Strasbourg, France.

ABSTRACT
Growing evidence supports a link between fatty acid metabolism and amyotrophic lateral sclerosis (ALS). Here we determined the fatty acid composition of blood lipids to identify markers of disease progression and survival. We enrolled 117 patients from two clinical centers and 48 of these were age and gender matched with healthy volunteers. We extracted total lipids from serum and blood cells, and separated fatty acid methyl esters by gas chromatography. We measured circulating biochemical parameters indicative of the metabolic status. Association between fatty acid composition and clinical readouts was studied, including ALS functional rating scale-revised (ALSFRS-R), survival, disease duration, site of onset and body mass index. Palmitoleate (16:1) and oleate (18:1) levels, and stearoyl-CoA desaturase indices (16:1/16:0 and 18:1/18:0) significantly increased in blood cells from ALS patients compared to healthy controls. Palmitoleate levels and 16:1/16:0 ratio in blood cells, but not body mass index or leptin concentrations, negatively correlated with ALSFRS-R decline over a six-month period (p<0.05). Multivariate Cox analysis, with age, body mass index, site of onset and ALSFRS-R as covariables, showed that blood cell 16:1/16:0 ratio was an independent prognostic factor for survival (hazard ratio=0.1 per unit of ratio, 95% confidence interval=0.01-0.57, p=0.009). In patients with high 16:1/16:0 ratio, survival at blood collection was extended by 10 months, as compared to patients with low ratio. The 16:1/16:0 index is an easy-to-handle parameter that predicts survival of ALS patients independently of body mass index. It therefore deserves further validation in larger cohorts for being used to assess disease outcome and effects of disease-modifying drugs.

No MeSH data available.


Related in: MedlinePlus

Blood cell 16:1/16:0 ratio correlates with disease progression and affects survival of ALS patients.Correlation between 16:1/16:0 and 18:0/18:1 ratios and disease duration (A, E) at blood collection or ALSFRS-R slope (B, F), determined as the decline of the score over a period of six months starting at the point of blood collection. Correlation coefficients (r) and p-values are indicated. n.s., non-significant p-value (Spearman test, n = 111). Based on the median ratio of the population, ALSFRS-R decline is shown in patients with low or high 16:1/16:0 ratio (C), and in patients with low or high 18:1/18:0 ratio (G). *p<0.05 (Mann-Withney test). (D, H) Kaplan-Meier curves of survival in the subgroups of patients as above. Survival was the interval between the point of blood collection and death. P-values are indicated (Gehan-Breslow-Wilcoxon test, n = 117).
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pone.0131512.g002: Blood cell 16:1/16:0 ratio correlates with disease progression and affects survival of ALS patients.Correlation between 16:1/16:0 and 18:0/18:1 ratios and disease duration (A, E) at blood collection or ALSFRS-R slope (B, F), determined as the decline of the score over a period of six months starting at the point of blood collection. Correlation coefficients (r) and p-values are indicated. n.s., non-significant p-value (Spearman test, n = 111). Based on the median ratio of the population, ALSFRS-R decline is shown in patients with low or high 16:1/16:0 ratio (C), and in patients with low or high 18:1/18:0 ratio (G). *p<0.05 (Mann-Withney test). (D, H) Kaplan-Meier curves of survival in the subgroups of patients as above. Survival was the interval between the point of blood collection and death. P-values are indicated (Gehan-Breslow-Wilcoxon test, n = 117).

Mentions: In a second step to identify biomarkers that could help to prognosticate ALS evolution, we performed a cross-section study with 117 ALS patients, including the previous 48 ones (S1 Table). We focused on SCD indices in blood cell pellets, since differences in this lipid fraction between patients and controls were more robust. None of the SCD indices correlated with the duration of the disease from symptom onset to time of blood collection (Fig 2A and 2B), suggesting the absence of interferences due to the variability in the time of sampling. In contrast, 16:1/16:0 ratio showed a significant negative correlation with disease progression (Fig 2C and 2D), which was defined as the loss of ALSFRS-R score over a period of six months (unit loss/month) [31]. In fact, levels of palmitoleate itself were also significantly associated with the decline of ALSFRS-R (r = -0.1996, p<0.05). The relationship between SCD index and disease progression was also apparent when patients were divided into two subsets of low and high 16:1/16:0 ratio, based on the median of the population. ALSFRS-R declined more slowly in patients with high 16:1/16:0 ratio than in patients with low 16:1/16:0 ratio. Other measured indices, including 18:1/18:0 ratio, PI and ARA/EPA ratio, were not significantly associated with the rate of disease progression (Fig 2E and 2F, data not shown). However, both SCD indices in blood cells correlated negatively with PI, indicating that a higher proportion of monounsaturated fatty acids is associated with a lower susceptibility to lipid peroxidation (S1 Fig).


Blood Cell Palmitoleate-Palmitate Ratio Is an Independent Prognostic Factor for Amyotrophic Lateral Sclerosis.

Henriques A, Blasco H, Fleury MC, Corcia P, Echaniz-Laguna A, Robelin L, Rudolf G, Lequeu T, Bergaentzle M, Gachet C, Pradat PF, Marchioni E, Andres CR, Tranchant C, Gonzalez De Aguilar JL, Loeffler JP - PLoS ONE (2015)

Blood cell 16:1/16:0 ratio correlates with disease progression and affects survival of ALS patients.Correlation between 16:1/16:0 and 18:0/18:1 ratios and disease duration (A, E) at blood collection or ALSFRS-R slope (B, F), determined as the decline of the score over a period of six months starting at the point of blood collection. Correlation coefficients (r) and p-values are indicated. n.s., non-significant p-value (Spearman test, n = 111). Based on the median ratio of the population, ALSFRS-R decline is shown in patients with low or high 16:1/16:0 ratio (C), and in patients with low or high 18:1/18:0 ratio (G). *p<0.05 (Mann-Withney test). (D, H) Kaplan-Meier curves of survival in the subgroups of patients as above. Survival was the interval between the point of blood collection and death. P-values are indicated (Gehan-Breslow-Wilcoxon test, n = 117).
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pone.0131512.g002: Blood cell 16:1/16:0 ratio correlates with disease progression and affects survival of ALS patients.Correlation between 16:1/16:0 and 18:0/18:1 ratios and disease duration (A, E) at blood collection or ALSFRS-R slope (B, F), determined as the decline of the score over a period of six months starting at the point of blood collection. Correlation coefficients (r) and p-values are indicated. n.s., non-significant p-value (Spearman test, n = 111). Based on the median ratio of the population, ALSFRS-R decline is shown in patients with low or high 16:1/16:0 ratio (C), and in patients with low or high 18:1/18:0 ratio (G). *p<0.05 (Mann-Withney test). (D, H) Kaplan-Meier curves of survival in the subgroups of patients as above. Survival was the interval between the point of blood collection and death. P-values are indicated (Gehan-Breslow-Wilcoxon test, n = 117).
Mentions: In a second step to identify biomarkers that could help to prognosticate ALS evolution, we performed a cross-section study with 117 ALS patients, including the previous 48 ones (S1 Table). We focused on SCD indices in blood cell pellets, since differences in this lipid fraction between patients and controls were more robust. None of the SCD indices correlated with the duration of the disease from symptom onset to time of blood collection (Fig 2A and 2B), suggesting the absence of interferences due to the variability in the time of sampling. In contrast, 16:1/16:0 ratio showed a significant negative correlation with disease progression (Fig 2C and 2D), which was defined as the loss of ALSFRS-R score over a period of six months (unit loss/month) [31]. In fact, levels of palmitoleate itself were also significantly associated with the decline of ALSFRS-R (r = -0.1996, p<0.05). The relationship between SCD index and disease progression was also apparent when patients were divided into two subsets of low and high 16:1/16:0 ratio, based on the median of the population. ALSFRS-R declined more slowly in patients with high 16:1/16:0 ratio than in patients with low 16:1/16:0 ratio. Other measured indices, including 18:1/18:0 ratio, PI and ARA/EPA ratio, were not significantly associated with the rate of disease progression (Fig 2E and 2F, data not shown). However, both SCD indices in blood cells correlated negatively with PI, indicating that a higher proportion of monounsaturated fatty acids is associated with a lower susceptibility to lipid peroxidation (S1 Fig).

Bottom Line: Palmitoleate (16:1) and oleate (18:1) levels, and stearoyl-CoA desaturase indices (16:1/16:0 and 18:1/18:0) significantly increased in blood cells from ALS patients compared to healthy controls.In patients with high 16:1/16:0 ratio, survival at blood collection was extended by 10 months, as compared to patients with low ratio.It therefore deserves further validation in larger cohorts for being used to assess disease outcome and effects of disease-modifying drugs.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U1118, Mécanismes Centraux et Périphériques de la Neurodégénerescence, Strasbourg, France; Université de Strasbourg, UMR_S1118, Fédération de Médecine Translationnelle, Strasbourg, France.

ABSTRACT
Growing evidence supports a link between fatty acid metabolism and amyotrophic lateral sclerosis (ALS). Here we determined the fatty acid composition of blood lipids to identify markers of disease progression and survival. We enrolled 117 patients from two clinical centers and 48 of these were age and gender matched with healthy volunteers. We extracted total lipids from serum and blood cells, and separated fatty acid methyl esters by gas chromatography. We measured circulating biochemical parameters indicative of the metabolic status. Association between fatty acid composition and clinical readouts was studied, including ALS functional rating scale-revised (ALSFRS-R), survival, disease duration, site of onset and body mass index. Palmitoleate (16:1) and oleate (18:1) levels, and stearoyl-CoA desaturase indices (16:1/16:0 and 18:1/18:0) significantly increased in blood cells from ALS patients compared to healthy controls. Palmitoleate levels and 16:1/16:0 ratio in blood cells, but not body mass index or leptin concentrations, negatively correlated with ALSFRS-R decline over a six-month period (p<0.05). Multivariate Cox analysis, with age, body mass index, site of onset and ALSFRS-R as covariables, showed that blood cell 16:1/16:0 ratio was an independent prognostic factor for survival (hazard ratio=0.1 per unit of ratio, 95% confidence interval=0.01-0.57, p=0.009). In patients with high 16:1/16:0 ratio, survival at blood collection was extended by 10 months, as compared to patients with low ratio. The 16:1/16:0 index is an easy-to-handle parameter that predicts survival of ALS patients independently of body mass index. It therefore deserves further validation in larger cohorts for being used to assess disease outcome and effects of disease-modifying drugs.

No MeSH data available.


Related in: MedlinePlus