Susceptibility to Infections, Tumor Risk and Liver Disease in Patients With Ataxia Telangiectasia

Susceptibility to Infections, Tumor Risk and Liver Disease in Patients With Ataxia Telangiectasia With and Without Substitution of Immunoglobulin G: a Prospective Observational Study

Ataxia telangiectasia (A-T) is a rare devastating human recessive disorder characterized by progressive cerebellar ataxia, immunodeficiency, chromosomal instability and cancer susceptibility. The immunodeficiency is expressed by recurring infections. It's characterised by decreased lymphocytes data as well as lack of immunglobulin A, immunglobulin G subclasses and specific antibodies against pneumococcus. Aim of the present clinical trial is to investigate frequency-, intensity- and duration of the infections as well as changes oft immune status, dimension of liver disease and tumor risk in patients with A-T, with and without immunoglobulin G substitution therapy. Transient elastography (FibroScan) will be performed in order to measure liver stiffness as an indication of fatty liver and liver fibrosis. A bioelectrical impedance analysis (BIA) is conducted to investigate the exact body composition. Ataxia Score is determined to define neurological problems. Every subject receives a diary to compile symptoms of infection.

Ataxia teleangiectasia (A-T) is a rare devastating human recessive disorder characterized by progressive cerebellar ataxia, immunodeficiency, chromosomal instability and cancer susceptibility. The immunodeficiency is expressed by recurring infections. It's characterised by decreased lymphocytes data as well as lack of immunglobulin A, immunglobulin G subclasses and specific antibodies against pneumococcus as shown in many trials. Additionally the patients suffer from a fatty liver with increased transaminases and have the risk for a cirrhosis of the liver and a hepatocellular carcinoma. It's known that the dimension of the liver disease affects susceptibility to infection. Nevertheless there are only a few studies treating this problem. Despite the proof of the immunodeficiency polyvalent immunoglobulins (IgG) are not given regularly. Own observations show that in spite of the treatment with immunoglobulins the progression of a chronic destructive lung disease with development of bronchiectasis hardly can prohibited. Up to now it isn't cleared if a substitution therapy with immunoglobulins reduces the susceptibility to infection. Therefore the aim oft the present clinical trial ist to explore frequency-, intensity, and duration oft the infections as well as changes oft the immune status, measure of liver disease and tumor risk in patients with A-T, with and without immunoglobulin therapy. The study includes five visits, which are performed in all A-T patients. Visit 1, 3, 5 are realized in the context of annual follow ups: To evaluate weight and length of all subjects To analyze the exact structure of single body compartments such as the lean mass, the water compartment or the fat compartment using bioelectrical impedance analysis To define the neurological status by ataxia score To get a detailed immune status, vaccination status and liver values as well as special tumor markers in blood To check the lung function using spirometry To measure liver stiffness using transient elastography (FibroScan) To compile any symptoms of infection by diary To investigate the ataxia status and physical condition by means of the Five-Times-Sit-to-Stand Test Visit 2 and 4 are additionally conducted as study visits: To get a detailed immune status in blood To check the lung function using spirometry

A-T patients aged 2 to 45 years with and without immunoglobulin G Substitution bioelectrical impedance Analysis blood draw transient elastography (FibroScan) ataxia score Five-Times-Sit-to-Stand Test

Electrophysical measurement that allows to determine the exact composition of single body compartments by producing a magnetic field and detecting the potential difference through the body

FibroScan is a noninvasive tool to measure liver stiffness as an indication of fatty liver and liver fibrosis using ultrasound

Klockgether ataxia score ranges from 0 to 35 points in which 0 means no symptoms and 35 stands for final stage of disease. It includes seven ataxia associated symptoms: dysarthria, intention tremor, ataxia of gait, stance, dysdiadochokinesia, upper limb and lower limb

The test measures the complete time which is necessary for an individual to stand up and sit down on a chair five times in series

Evaluation of frequency, severity and intensity of infections in A-T patients with and without immunoglobulin G substitution

Evaluation of the degree of liver disease measured by liver enzymes and structural changes by transient elastography (Fibroscan) in A-T patients

Inclusion Criteria: aim group: genetically and/or clinically diagnosed A-T age 2-45 years written informed consent Exclusion Criteria: age < 2 or > 45 years other diseases with influence on the immune system (i.e. diabetes mellitus, malignoma, dialysis-dependent renal failure)

Zielen S, Duecker RP, Woelke S, Donath H, Bakhtiar S, Buecker A, Kreyenberg H, Huenecke S, Bader P, Mahlaoui N, Ehl S, El-Helou SM, Pietrucha B, Plebani A, van der Flier M, van Aerde K, Kilic SS, Reda SM, Kostyuchenko L, McDermott E, Galal N, Pignata C, Perez JLS, Laws HJ, Niehues T, Kutukculer N, Seidel MG, Marques L, Ciznar P, Edgar JDM, Soler-Palacin P, von Bernuth H, Krueger R, Meyts I, Baumann U, Kanariou M, Grimbacher B, Hauck F, Graf D, Granado LIG, Prader S, Reisli I, Slatter M, Rodriguez-Gallego C, Arkwright PD, Bethune C, Deripapa E, Sharapova SO, Lehmberg K, Davies EG, Schuetz C, Kindle G, Schubert R. Simple Measurement of IgA Predicts Immunity and Mortality in Ataxia-Telangiectasia. J Clin Immunol. 2021 Nov;41(8):1878-1892. doi: 10.1007/s10875-021-01090-8. Epub 2021 Sep 3.