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Diabetic Nephropathy Assessment: Microtubule-Associated Protein 1 Light-Chain 3B a New Promising Biomarker.

ABSTRACT: Autophagy is a highly conserved pathway. Impairment of autophagy is implicated in the pathogenesis of diabetic nephropathy. The current study applied a bioinformatics analysis to retrieve promising autophagy biomarker relevant diabetic nephropathy. Urinary expression of Microtubule-associated protein 1 light-chain 3B (LC3B) RNA was assessed. Urine samples of 86 type II diabetic kidney disease Egyptian patients (albuminuria group) were provided to quantify urinary expression of LC3B. A group of 30 healthy volunteers were also enrolled in addition to non-albuminuria group including 44 patients. Our study revealed a cut-off value for urinary LC3B expression level that was calculated by receiver-operating characteristic curve as 0.866. Sensitivity and specificity of LC3B were 83.7 and 78.4% respectively. The positivity rate of urinary LC3B expression level was significantly lower in diabetic nephropathy patients than control group. LC3B has great clinical value as promising biomarker in diabetic nephropathy assessment.

SUBMITTER: Mohamed MM

PROVIDER: S-EPMC6801283 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Diabetic Nephropathy Assessment: Microtubule-Associated Protein 1 Light-Chain 3B a New Promising Biomarker.

Mohamed Magdy M MM Eissa Sanaa S Mostafa Mona M Hegazy Marwa G A MGA

Indian journal of clinical biochemistry : IJCB 20180622 4

Autophagy is a highly conserved pathway. Impairment of autophagy is implicated in the pathogenesis of diabetic nephropathy. The current study applied a bioinformatics analysis to retrieve promising autophagy biomarker relevant diabetic nephropathy. Urinary expression of Microtubule-associated protein 1 light-chain 3B (LC3B) RNA was assessed. Urine samples of 86 type II diabetic kidney disease Egyptian patients (albuminuria group) were provided to quantify urinary expression of LC3B. A group of 3 ...[more]

PMID: 31686735

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Project description:BACKGROUND:Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of autosomal dominantly inherited spinocerebellar ataxias (SCAs). No validated blood biomarker is available to assess either disease progression or therapeutic response. Neurofilament light chain (NfL) was recently proposed as a serum biomarker for many neurodegenerative disorders. The present study investigated whether NfL was a promising serum biomarker for SCA3. METHODS:Seventeen SCA3 patients and 9 controls were enrolled in cohort A, and 116 SCA3 individuals (preclinical and patients) and 91 controls were recruited as cohort B. We assessed whether serum NfL correlated with cerebrospinal fluid (CSF) NfL in cohort A and correlations between serum NfL levels and clinical features and brain volumes were determined in cohort B. The single-molecule array method was used to measure serum NfL levels. Disease severity was determined using the scale for the assessment and rating of ataxia (SARA) and the international cooperative ataxia rating scale (ICARS). Cerebellar and brainstem volumes were assessed using MRI neuroimaging measurements. RESULTS:Serum/CSF NfL levels in cohort A were elevated in SCA3 patients, and serum and CSF NfL exhibited a significant positive correlation (r = 0.9179, p < 0.0001). Levels of serum NfL in cohort B were significantly higher in preclinical SCA3 (15.03 ± 7.49 vs 6.88 ± 2.72 pg/ mL, p < 0.0001) and manifest SCA3 subjects (37.56 ± 13.47 vs 9.07 ± 6.02 pg/ mL, p < 0.0001) compared to those in controls. Serum NfL concentrations increased from early disease stage to the next stage. Levels of serum NfL in ATXN3 mutation carriers were positively associated with SARA (r = 0.5458, p < 0.0001) and ICARS scores (r = 0.5522, p < 0.0001). Significant negative associations with cerebellar volumes (r = - 0.4217, p = 0.0003) and brainstem volumes (r = - 0.4263, p = 0.0003) were observed. All changes remained significant after adjustment for age and CAG repeat. CONCLUSIONS:Levels of serum NfL were significantly elevated in SCA3 individuals and correlated with disease severity. Serum NfL is a promising serum biomarker of disease onset and progression, and a potential candidate biomarker of treatment response in SCA3.

Project description:Aims/hypothesisNo established blood-based biomarker exists to monitor diabetic sensorimotor polyneuropathy (DSPN) and evaluate treatment response. The neurofilament light chain (NFL), a blood biomarker of neuroaxonal damage in several neurodegenerative diseases, represents a potential biomarker for DSPN. We hypothesised that higher serum NFL levels are associated with prevalent DSPN and nerve dysfunction in individuals recently diagnosed with diabetes.MethodsThis cross-sectional study included 423 adults with type 1 and type 2 diabetes and known diabetes duration of less than 1 year from the prospective observational German Diabetes Study cohort. NFL was measured in serum samples of fasting participants in a multiplex approach using proximity extension assay technology. DSPN was assessed by neurological examination, nerve conduction studies and quantitative sensory testing. Associations of serum NFL with DSPN (defined according to the Toronto Consensus criteria) were estimated using Poisson regression, while multivariable linear and quantile regression models were used to assess associations with nerve function measures. In exploratory analyses, other biomarkers in the multiplex panel were also analysed similarly to NFL.ResultsDSPN was found in 16% of the study sample. Serum NFL levels increased with age. After adjustment for age, sex, waist circumference, height, HbA1c, known diabetes duration, diabetes type, cholesterol, eGFR, hypertension, CVD, use of lipid-lowering drugs and use of non-steroidal anti-inflammatory drugs, higher serum NFL levels were associated with DSPN (RR [95% CI] per 1-normalised protein expression increase, 1.92 [1.50, 2.45], p<0.0001), slower motor (all p<0.0001) and sensory (all p≤0.03) nerve conduction velocities, lower sural sensory nerve action potential (p=0.0004) and higher thermal detection threshold to warm stimuli (p=0.023 and p=0.004 for hand and foot, respectively). There was no evidence for associations between other neurological biomarkers and DSPN or nerve function measures.Conclusions/interpretationOur findings in individuals recently diagnosed with diabetes provide new evidence associating higher serum NFL levels with DSPN and peripheral nerve dysfunction. The present study advocates NFL as a potential biomarker for DSPN.

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Diabetic Nephropathy Assessment: Microtubule-Associated Protein 1 Light-Chain 3B a New Promising Biomarker.

Publications

Diabetic Nephropathy Assessment: Microtubule-Associated Protein 1 Light-Chain 3B a New Promising Biomarker.

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