Liver Assessment in Patients with Ataxia-Telangiectasia: Transient Elastography Detects Early Stages of Steatosis and Fibrosis.

Background: Ataxia-telangiectasia (A-T) is a rare autosomal-recessive multisystem disorder characterized by pronounced cerebellar ataxia, telangiectasia, cancer predisposition, and altered body composition. Liver diseases with steatosis, fibrosis, and hepatocellular carcinoma are frequent findings in older patients but sensitive noninvasive diagnostic tools are lacking. Objectives: To determine the sensitivity of transient elastography (TE) as a screening tool for early hepatic tissue changes and serum biomarkers for liver disease. Methods: Thirty-one A-T patients aged 2 to 25 years were examined prospectively from 2016-2018 by TE. In addition, we evaluated the diagnostic performance of liver biomarkers for steatosis and necroinflammatory activity (SteatoTest and ActiTest, Biopredictive, Paris) compared to TE. For calculation and comparison, patients were divided into two groups (<12, >12 years of age). Results: TE revealed steatosis in 2/21 (10%) younger patients compared to 9/10 (90%) older patients. Fibrosis was present in 3/10 (30%) older patients as assessed by TE. We found a significant correlation of steatosis with SteatoTest, alpha-fetoprotein (AFP), HbA1c, and triglycerides. Liver stiffness correlated significantly with SteatoTest, ActiTest, HbA1c, and triglycerides. Conclusion: Liver disease is a common finding in older A-T patients. TE is an objective measure to detect early stages of steatosis and fibrosis. SteatoTest and ActiTest are a good diagnostic assessment for steatosis and necroinflammatory activity in patients with A-T and confirmed the TE results.

Neurofilament Light Chain Is a Biomarker of Neurodegeneration in Ataxia Telangiectasia.

Ataxia telangiectasia (A-T) is a progressive and life-limiting disease associated with cerebellar ataxia due to progressive cerebellar degeneration. In addition to ataxia, which is described in detail, the presence of chorea, dystonia, oculomotor apraxia, athetosis, parkinsonism, and myoclonia are typical manifestations of the disease. The study aimed to evaluate the specificity and sensitivity of neurofilament light chain (NfL) as a biomarker of neurodegeneration in relation to SARA score. In this prospective trial, one visit of 42 A-T patients aged 1.3-25.6 years (mean 11.6 ± 7.3 years) was performed, in which NfL was determined from serum by ELISA. Additionally, a neurological examination of the patients was performed. Blood was collected from 19 healthy volunteers ≥ 12 years of age. We found significantly increased levels of NfL in patients with A-T compared to healthy controls (21.5 ± 3.6 pg/mL vs. 9.3 ± 0.49 pg/mL, p ≤ 0.01). There was a significant correlation of NfL with age, AFP, and SARA. NfL is a new potential progression biomarker in blood for neurodegeneration in A-T which increases with age.

Altered Cerebrospinal Fluid (CSF) in Children with Ataxia Telangiectasia.

Ataxia telangiectasia (A-T) is a devastating multi-system disorder characterized by progressive cerebellar ataxia and immunodeficiency. The neurological decline may be caused by multiple factors of which ongoing inflammation and oxidative stress may play a dominant role. The objective of the present investigation was to determine cerebrospinal fluid (CSF) proteins and possible low-grade inflammation and its relation to age and neurological deterioration. In the present study, we investigated 15 patients with A-T from 2 to 16 years. Our investigation included blood and CSF tests, clinical neurological examination, A-T score, and MRI findings. The albumin ratio (AR) was analyzed to determine the blood-brain-barrier function. In addition, inflammatory cytokines (IL-1α, IL-6, IL-8, IL-12 p40, IL-17A, IFN-γ, TNF-α) were measured by the multiplex cytometric bead array. We compared the results with those from an age-matched control group. Three of the A-T patients were analyzed separately (one after resection of a cerebral meningioma, one after radiation and chemotherapy due to leukemia, one after stem cell transplantation). Patient had significantly more moderate and severe side effects due to CSF puncture (vomiting, headache, need for anti-emetic drugs) compared with healthy controls. Total protein, albumin, and the AR increased with age indicating a disturbed blood barrier function in older children. There were no differences for cytokines in serum and CSF with the exception of IL-2, which was significantly higher in controls in serum. The AR is significantly altered in A-T patients, but low-grade inflammation is not detectable in serum and CSF.

Calprotectin as a New Sensitive Marker of Neutrophilic Inflammation in Patients with Bronchiolitis Obliterans.

INTRODUCTION: Bronchiolitis obliterans (BO) is a chronic disease in which persistent inflammation leads to obstruction and obliteration of the small airways. The aim of this study was to evaluate the value of calprotectin as an inflammatory marker in induced sputum. METHODS: Twenty-eight patients suffering from BO and 18 healthy controls were examined. Lung function was measured by spirometry, body plethysmography, and lung clearance index (LCI). The induced sputum was obtained, cell counts were performed, and cytokines were measured using cytometric bead array (CBA). Calprotectin was quantified in the sputum and serum samples using commercially available sandwich ELISA. RESULTS: Spirometry parameters including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and maximum expiratory flow rate at 25% vital capacity (MEF25) were significantly lower in BO patients than in healthy controls, whereas the reserve volume (RV), RV to total lung capacity ratio (RV/TLC), and LCI were significantly increased. In sputum, calprotectin levels, neutrophils, and IL-8 were significantly elevated. Calprotectin levels correlated strongly with IL-8 and other biomarkers, neutrophils FEV1 and MEF25. In serum, calprotectin was significantly diminished in BO patients compared to controls. CONCLUSION: Lung function is severely impaired in BO patients. Calprotectin is significantly elevated in the sputum of BO patients and reflects ongoing neutrophilic inflammation.