scholarly journals IL6 receptor358Ala variant and trans-signaling are disease modifiers in amyotrophic lateral sclerosis

2019 ◽  
Vol 6 (6) ◽  
pp. e631 ◽  
Author(s):  
Marlena Wosiski-Kuhn ◽  
Mac Robinson ◽  
Jane Strupe ◽  
Phonepasong Arounleut ◽  
Matthew Martin ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Disease Progression ◽  
Interleukin 6 ◽  
Serum Levels ◽  
Interleukin 6 Receptor ◽  
The Common ◽  
Paired Serum ◽  
Control Study ◽  
Lateral Sclerosis

ObjectiveTo test the hypothesis that patients with amyotrophic lateral sclerosis (ALS) inheriting the common interleukin 6 receptor (IL6R) coding variant (Asp358Ala, rs2228145, C allele) have associated increases in interleukin 6 (IL6) and IL6R levels in serum and CSF and faster disease progression than noncarriers.MethodsAn observational, case-control study of paired serum and CSF of 47 patients with ALS, 46 healthy, and 23 neurologic disease controls from the Northeastern ALS Consortium Biofluid Repository (cohort 1) was performed to determine serum levels of IL6, sIL6R, and soluble glycoprotein 130 and compared across groups and IL6R genotype. Clinical data regarding disease progression from a separate cohort of 35 patients with ALS from the Wake Forest ALS Center (cohort 2) were used to determine change in ALSFRS-R scores by genotype.ResultsPatients with ALS had increased CSF IL6 levels compared with healthy (p < 0.001) and neurologic (p = 0.021) controls. Patients with ALS also had increased serum IL6 compared with healthy (p = 0.040) but not neurologic controls. Additive allelic increases in serum IL6R were observed in all groups (average increase of 52% with the presence of the IL6R C allele; p < 0.001). However, only subjects with ALS had significantly increased CSF sIL6R levels compared with controls (p < 0.001). When compared across genotypes, only patients with ALS inheriting the IL6R C allele exhibit increased CSF IL6. ALSFRS-R scores decreased more in patients with ALS with the IL6R C allele than in those without (p = 0.019).ConclusionsTheses results suggest that for individuals inheriting the IL6R C allele, the cytokine exerts a disease- and location-specific role in ALS. Follow-up, prospective studies are necessary, as this subgroup of patients may be identified as ideally responsive to IL6 receptor–blocking therapies.

scholarly journals Rather than Rs1800796 Polymorphism, Expression of Interleukin-6 Is Associated with Disease Progression of Chronic HBV Infection in a Chinese Han Population

2013 ◽  
Vol 35 ◽  
pp. 799-805 ◽  
Author(s):  
Shengli Tang ◽  
Zhisu Liu ◽  
Yongxi Zhang ◽  
Yueming He ◽  
Dingyu Pan ◽  
...  
Keyword(s):  
Disease Progression ◽  
Interleukin 6 ◽  
Staging System ◽  
Serum Levels ◽  
Hbv Infection ◽  
Healthy Controls ◽  
Chinese Han ◽  
Chronic Hbv Infection ◽  
Chronic Hbv ◽  
Control Study

Interleukin-6 plays an important role in chronic inflammation as well as tumor growth and progression. Here, a case-control study was undertaken to investigate the association of rs1800796 polymorphism of IL-6 gene and serum levels with disease progression of chronic HBV infection. Rs1800796 polymorphism was genotyped in 641 Chinese Han patients with chronic HBV infection, including 23 IT, 25 IC, 292 CHB, 153 LC, and 148 HCC patients and 265 healthy controls. Serum IL-6 levels were measured in 23 IT, 25 IC, 47 CHB, 41 LC, and 49 HCC patients and 45 healthy controls, and the classifications of HCC were accorded to BCLC staging system. We found no significant association between rs1800796 polymorphism and disease progression of chronic HBV infection; however, serum IL-6 levels showed significant statistical differences between patients with CHB, LC, and HCC. Moreover, statistical differences can be observed in patients with terminal stage HCC compared with those of early to intermediate or advanced stage HCC. Our findings suggest that rs1800796 polymorphism unlikely contribute significantly to affect the progression of chronic HBV infection, and serum IL-6 levels can act as a useful indicator for disease progression and severity of chronic HBV infection.

scholarly journals Neurochemical correlates of functional decline in amyotrophic lateral sclerosis

2018 ◽  
Vol 90 (3) ◽  
pp. 294-301 ◽  
Author(s):  
Ian Cheong ◽  
Dinesh K Deelchand ◽  
Lynn E Eberly ◽  
Małgorzata Marjańska ◽  
Georgios Manousakis ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Cortex ◽  
Disease Progression ◽  
Upper Limb ◽  
Functional Decline ◽  
Body Regions ◽  
Neurochemical Changes ◽  
Lateral Sclerosis ◽  
Over Time

ObjectiveTo determine whether proton magnetic resonance spectroscopy (1H-MRS) can detect neurochemical changes in amyotrophic lateral sclerosis (ALS) associated with heterogeneous functional decline.MethodsNineteen participants with early-stage ALS and 18 age-matched and sex ratio-matched controls underwent ultra-high field 1H-MRS scans of the upper limb motor cortex and pons, ALS Functional Rating Scale-Revised (ALSFRS-R total, upper limb and bulbar) and upper motor neuron burden assessments in a longitudinal observational study design with follow-up assessments at 6 and 12 months. Slopes of neurochemical levels over time were compared between patient subgroups classified by the rate of upper limb or bulbar functional decline. 1H-MRS and clinical ratings at baseline were assessed for ability to predict study withdrawal due to disease progression.ResultsMotor cortex total N-acetylaspartate to myo-inositol ratio (tNAA:mIns) significantly declined in patients who worsened in upper limb function over the follow-up period (n=9, p=0.002). Pons glutamate + glutamine significantly increased in patients who worsened in bulbar function (n=6, p<0.0001). Neurochemical levels did not change in patients with stable function (n=5–6) or in healthy controls (n=14–16) over time. Motor cortex tNAA:mIns and ALSFRS-R at baseline were significantly lower in patients who withdrew from follow-up due to disease progression (n=6) compared with patients who completed the 12-month scan (n=10) (p<0.001 for tNAA:mIns; p<0.01 for ALSFRS-R), with a substantially larger overlap in ALSFRS-R between groups.ConclusionNeurochemical changes in motor areas of the brain are associated with functional decline in corresponding body regions. 1H-MRS was a better predictor of study withdrawal due to ALS progression than ALSFRS-R.

scholarly journals Clinical Determinants of Disease Progression in Amyotrophic Lateral Sclerosis—A Retrospective Cohort Study

2021 ◽  
Vol 10 (8) ◽  
pp. 1623
Author(s):  
Maria Viktoria Requardt ◽  
Dennis Görlich ◽  
Torsten Grehl ◽  
Matthias Boentert
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Disease Progression ◽  
Rating Scale ◽  
Rapid Decline ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Hazard Ratios ◽  
Sum Score ◽  
Lateral Sclerosis

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is ultimately fatal but characterized by substantial phenotypic heterogeneity, which is known to impact long-term course and survival. This study investigated clinical determinants of disease progression and outcome in a large cohort of patients with ALS. Methods: Retrospective analysis included comprehensive data from 625 patients who attended a tertiary ALS centre at least twice. Patients were stratified according to five distinct clinical phenotypes: classical ALS; bulbar ALS; ALS with frontotemporal dementia (ALS-FTD); upper motor neuron predominant (UMNP); and lower motor neuron predominant (LMNP). Results: This study confirmed higher age at symptom onset, shorter latency to diagnosis and more rapid decline in the revised ALS Functional Rating Scale sum score as predictors of poor prognosis. Hazard ratios for shorter survival were higher in patients with ALS-FTD versus classical ALS, and in patients with versus without chronic obstructive pulmonary disease (COPD). Mean survival was longest in the UMNP phenotype group. Conclusions: This study confirmed established predictors of shorter survival in ALS and showed that concomitant COPD in particular relates to poor outcome.

Intravenous infusion of mesenchymal stem cells delays disease progression in the SOD1G93A transgenic amyotrophic lateral sclerosis rat model

2021 ◽  
Vol 1757 ◽  
pp. 147296
Author(s):  
Hirotoshi Magota ◽  
Masanori Sasaki ◽  
Yuko Kataoka-Sasaki ◽  
Shinichi Oka ◽  
Ryo Ukai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Amyotrophic Lateral Sclerosis ◽  
Mesenchymal Stem Cells ◽  
Disease Progression ◽  
Rat Model ◽  
Intravenous Infusion ◽  
Lateral Sclerosis
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