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Humoral factors in ALS patients during disease progression.

Ehrhart J, Smith AJ, Kuzmin-Nichols N, Zesiewicz TA, Jahan I, Shytle RD, Kim SH, Sanberg CD, Vu TH, Gooch CL, Sanberg PR, Garbuzova-Davis S - J Neuroinflammation (2015)

Bottom Line: The purpose of the study was to identify humoral effectors as potential biomarkers during disease progression.Our results demonstrated a systemic pro-inflammatory state and impaired antioxidant system in ALS patients during disease progression.These novel findings, showing dynamic changes in humoral effectors during disease progression, could be important for development of an effective treatment for ALS.

View Article: PubMed Central - PubMed

Affiliation: Saneron CCEL Therapeutics, Inc., Tampa, FL, USA. jehrhar1@health.usf.edu.

ABSTRACT

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting upper and lower motor neurons in the CNS and leading to paralysis and death. There are currently no effective treatments for ALS due to the complexity and heterogeneity of factors involved in motor neuron degeneration. A complex of interrelated effectors have been identified in ALS, yet systemic factors indicating and/or reflecting pathological disease developments are uncertain. The purpose of the study was to identify humoral effectors as potential biomarkers during disease progression.

Methods: Thirteen clinically definite ALS patients and seven non-neurological controls enrolled in the study. Peripheral blood samples were obtained from each ALS patient and control at two visits separated by 6 months. The Revised ALS Functional Rating Scale (ALSFRS-R) was used to evaluate overall ALS-patient functional status at each visit. Eleven humoral factors were analyzed in sera. Cytokine levels (GM-CSF, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and TNF-α) were determined using the Bio-Rad Bio-Plex® Luminex 200 multiplex assay system. Nitrite, a breakdown product of NO, was quantified using a Griess Reagent System. Glutathione (GSH) concentrations were measured using a Glutathione Fluorometric Assay Kit.

Results: ALS patients had ALSFRS-R scores of 30.5 ± 1.9 on their first visit and 27.3 ± 2.7 on the second visit, indicating slight disease progression. Serum multiplex cytokine panels revealed statistically significant changes in IL-2, IL-5, IL-6, and IL-8 levels in ALS patients depending on disease status at each visit. Nitrite serum levels trended upwards in ALS patients while serum GSH concentrations were drastically decreased in sera from ALS patients versus controls at both visits.

Conclusions: Our results demonstrated a systemic pro-inflammatory state and impaired antioxidant system in ALS patients during disease progression. Increased levels of pro-inflammatory IL-6, IL-8, and nitrite and significantly decreased endogenous antioxidant GSH levels could identify these humoral constituents as systemic biomarkers for ALS. However, systemic changes in IL-2, IL-5, and IL-6 levels determined between visits in ALS patients might indicate adaptive immune system responses dependent on current disease stage. These novel findings, showing dynamic changes in humoral effectors during disease progression, could be important for development of an effective treatment for ALS.

No MeSH data available.


Related in: MedlinePlus

Serum nitrite levels. Nitrite concentrations were assayed in sera of ALS patients and controls at both visits using a Griess Reagent System. Nitrite levels were higher in ALS sera than control sera on both visits, but the differences were not statistically significant (p = 0.09). Results are plotted as mean ± SEM. Statistical significance was determined using two-tailed t-tests (* p < 0.05, ** p < 0.01)
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Fig2: Serum nitrite levels. Nitrite concentrations were assayed in sera of ALS patients and controls at both visits using a Griess Reagent System. Nitrite levels were higher in ALS sera than control sera on both visits, but the differences were not statistically significant (p = 0.09). Results are plotted as mean ± SEM. Statistical significance was determined using two-tailed t-tests (* p < 0.05, ** p < 0.01)

Mentions: Serum samples were assayed to measure concentrations of nitrite, a breakdown product of NO. At both visits, sera from ALS patients contained higher concentrations of nitrite (first visit—65.33 ± 12.38 μM, second visit—69.12 ± 21.29 μM) than the control sera (first visit—44.94 ± 9.32 μM, second visit—36.01 ± 3.70 μM) (Fig. 2). However, concentration was higher in ALS sera with a slight increase at the second visit of ALS patients; differences versus controls were not statistically significant (p = 0.09) at either visit.Fig. 2


Humoral factors in ALS patients during disease progression.

Ehrhart J, Smith AJ, Kuzmin-Nichols N, Zesiewicz TA, Jahan I, Shytle RD, Kim SH, Sanberg CD, Vu TH, Gooch CL, Sanberg PR, Garbuzova-Davis S - J Neuroinflammation (2015)

Serum nitrite levels. Nitrite concentrations were assayed in sera of ALS patients and controls at both visits using a Griess Reagent System. Nitrite levels were higher in ALS sera than control sera on both visits, but the differences were not statistically significant (p = 0.09). Results are plotted as mean ± SEM. Statistical significance was determined using two-tailed t-tests (* p < 0.05, ** p < 0.01)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4487852&req=5

Fig2: Serum nitrite levels. Nitrite concentrations were assayed in sera of ALS patients and controls at both visits using a Griess Reagent System. Nitrite levels were higher in ALS sera than control sera on both visits, but the differences were not statistically significant (p = 0.09). Results are plotted as mean ± SEM. Statistical significance was determined using two-tailed t-tests (* p < 0.05, ** p < 0.01)
Mentions: Serum samples were assayed to measure concentrations of nitrite, a breakdown product of NO. At both visits, sera from ALS patients contained higher concentrations of nitrite (first visit—65.33 ± 12.38 μM, second visit—69.12 ± 21.29 μM) than the control sera (first visit—44.94 ± 9.32 μM, second visit—36.01 ± 3.70 μM) (Fig. 2). However, concentration was higher in ALS sera with a slight increase at the second visit of ALS patients; differences versus controls were not statistically significant (p = 0.09) at either visit.Fig. 2

Bottom Line: The purpose of the study was to identify humoral effectors as potential biomarkers during disease progression.Our results demonstrated a systemic pro-inflammatory state and impaired antioxidant system in ALS patients during disease progression.These novel findings, showing dynamic changes in humoral effectors during disease progression, could be important for development of an effective treatment for ALS.

View Article: PubMed Central - PubMed

Affiliation: Saneron CCEL Therapeutics, Inc., Tampa, FL, USA. jehrhar1@health.usf.edu.

ABSTRACT

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting upper and lower motor neurons in the CNS and leading to paralysis and death. There are currently no effective treatments for ALS due to the complexity and heterogeneity of factors involved in motor neuron degeneration. A complex of interrelated effectors have been identified in ALS, yet systemic factors indicating and/or reflecting pathological disease developments are uncertain. The purpose of the study was to identify humoral effectors as potential biomarkers during disease progression.

Methods: Thirteen clinically definite ALS patients and seven non-neurological controls enrolled in the study. Peripheral blood samples were obtained from each ALS patient and control at two visits separated by 6 months. The Revised ALS Functional Rating Scale (ALSFRS-R) was used to evaluate overall ALS-patient functional status at each visit. Eleven humoral factors were analyzed in sera. Cytokine levels (GM-CSF, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and TNF-α) were determined using the Bio-Rad Bio-Plex® Luminex 200 multiplex assay system. Nitrite, a breakdown product of NO, was quantified using a Griess Reagent System. Glutathione (GSH) concentrations were measured using a Glutathione Fluorometric Assay Kit.

Results: ALS patients had ALSFRS-R scores of 30.5 ± 1.9 on their first visit and 27.3 ± 2.7 on the second visit, indicating slight disease progression. Serum multiplex cytokine panels revealed statistically significant changes in IL-2, IL-5, IL-6, and IL-8 levels in ALS patients depending on disease status at each visit. Nitrite serum levels trended upwards in ALS patients while serum GSH concentrations were drastically decreased in sera from ALS patients versus controls at both visits.

Conclusions: Our results demonstrated a systemic pro-inflammatory state and impaired antioxidant system in ALS patients during disease progression. Increased levels of pro-inflammatory IL-6, IL-8, and nitrite and significantly decreased endogenous antioxidant GSH levels could identify these humoral constituents as systemic biomarkers for ALS. However, systemic changes in IL-2, IL-5, and IL-6 levels determined between visits in ALS patients might indicate adaptive immune system responses dependent on current disease stage. These novel findings, showing dynamic changes in humoral effectors during disease progression, could be important for development of an effective treatment for ALS.

No MeSH data available.


Related in: MedlinePlus