Dataset Information

Serum Interleukin-6 Levels and Pulmonary Function in Ataxia-Telangiectasia.

ABSTRACT: To evaluate the potential link between systemic inflammation and impaired lung function in people with ataxia-telangiectasia (A-T), we hypothesized that serum levels of interleukin (IL)-6, a proinflammatory cytokine, would correlate inversely with lung function in subjects with A-T.Consecutive subjects with A-T were recruited from the Johns Hopkins Outpatient A-T Clinical Center. Serum levels of IL-6 and 8 were measured by enzyme-linked immunosorbent assay. Spirometry was performed in subjects ≥ 6 years of age on the same day that serum was obtained for measurements of cytokines.Approximately 80% of subjects had elevated serum IL-6 levels (> 1.0 pg/mL). No association was found between elevated IL-6 and age. Elevated IL-8 levels were found in 23.6% of subjects, and all subjects with elevated IL-8 levels had elevated IL-6 levels. Subjects with elevated IL-6 levels (mean: 6.14 ± 7.47 pg/mL) had significantly lower mean percent forced vital capacity (FVC%, 50.5% ± 17.8%) compared with subjects with normal serum IL-6 levels (FVC% of 66.2 ± 16.1, P = .018). Greater IL-6 levels were associated with lower FVC% even after adjustment for receiving gamma globulin therapy (P = .024) and supplemental nutrition (P = .055).An association was found between elevated serum IL-6 levels and lower lung function in subjects with A-T. In addition, subjects with both elevated IL-6 and IL-8 had the lowest mean lung function. These findings indicate that markers for systemic inflammation may be useful in identifying individuals with A-T at increased risk for lower lung function and may help in assessing response to therapy.

SUBMITTER: McGrath-Morrow SA

PROVIDER: S-EPMC5562399 | biostudies-other | 2016 Apr

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:Ataxia telangiectasia (A-T) is an autosomal recessive disorder primarily characterized by cerebellar degeneration, telangiectasia, immunodeficiency, cancer susceptibility and radiation sensitivity. A-T is often referred to as a genome instability or DNA damage response syndrome.The world-wide prevalence of A-T is estimated to be between 1 in 40,000 and 1 in 100,000 live births.A-T is a complex disorder with substantial variability in the severity of features between affected individuals, and at different ages. Neurological symptoms most often first appear in early childhood when children begin to sit or walk. They have immunological abnormalities including immunoglobulin and antibody deficiencies and lymphopenia. People with A-T have an increased predisposition for cancers, particularly of lymphoid origin. Pulmonary disease and problems with feeding, swallowing and nutrition are common, and there also may be dermatological and endocrine manifestations.A-T is caused by mutations in the ATM (Ataxia Telangiectasia, Mutated) gene which encodes a protein of the same name. The primary role of the ATM protein is coordination of cellular signaling pathways in response to DNA double strand breaks, oxidative stress and other genotoxic stress.The diagnosis of A-T is usually suspected by the combination of neurologic clinical features (ataxia, abnormal control of eye movement, and postural instability) with one or more of the following which may vary in their appearance: telangiectasia, frequent sinopulmonary infections and specific laboratory abnormalities (e.g. IgA deficiency, lymphopenia especially affecting T lymphocytes and increased alpha-fetoprotein levels). Because certain neurological features may arise later, a diagnosis of A-T should be carefully considered for any ataxic child with an otherwise elusive diagnosis. A diagnosis of A-T can be confirmed by the finding of an absence or deficiency of the ATM protein or its kinase activity in cultured cell lines, and/or identification of the pathological mutations in the ATM gene.There are several other neurologic and rare disorders that physicians must consider when diagnosing A-T and that can be confused with A-T. Differentiation of these various disorders is often possible with clinical features and selected laboratory tests, including gene sequencing.Antenatal diagnosis can be performed if the pathological ATM mutations in that family have been identified in an affected child. In the absence of identifying mutations, antenatal diagnosis can be made by haplotype analysis if an unambiguous diagnosis of the affected child has been made through clinical and laboratory findings and/or ATM protein analysis.Genetic counseling can help family members of a patient with A-T understand when genetic testing for A-T is feasible, and how the test results should be interpreted.Treatment of the neurologic problems associated with A-T is symptomatic and supportive, as there are no treatments known to slow or stop the neurodegeneration. However, other manifestations of A-T, e.g. immunodeficiency, pulmonary disease, failure to thrive and diabetes can be treated effectively.

Project description:Ataxia-telangiectasia (A-T) is an autosomal recessive multi-system disorder caused by mutation in the ataxia-telangiectasia mutated gene (ATM). ATM is a large serine/threonine protein kinase, a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) family whose best-studied function is as master controller of signal transduction for the DNA damage response (DDR) in the event of double strand breaks (DSBs). The DDR rapidly recognizes DNA lesions and initiates the appropriate cellular programs to maintain genome integrity. This includes the coordination of cell-cycle checkpoints, transcription, translation, DNA repair, metabolism, and cell fate decisions, such as apoptosis or senescence. DSBs can be generated by exposure to ionizing radiation (IR) or various chemical compounds, such as topoisomerase inhibitors, or can be part of programmed generation and repair of DSBs via cellular enzymes needed for the generation of the antibody repertoire as well as the maturation of germ cells. AT patients have immunodeficiency, and are sterile with gonadal dysgenesis as a result of defect in meiotic recombination. In the cells of nervous system ATM has additional role in vesicle dynamics as well as in the maintenance of the epigenetic code of histone modifications. Moderate levels of ATM are associated with prolonged lifespan through resistance to oxidative stress. ATM inhibitors are being viewed as potential radiosensitizers as part of cancer radiotherapy. Though there is no cure for the disease at present, glucocorticoids have been shown to induce alternate splicing site in the gene for ATM partly restoring its activity, but their most effective timing in the disease natural history is not yet known. Gene therapy is promising but large size of the gene makes it technically difficult to be delivered across the blood-brain barrier at present. As of now, apart from glucocorticoids, use of histone deacetylase inhibitors/EZH2 to minimize effect of the absence of ATM, looks more promising.

Dataset Information

Serum Interleukin-6 Levels and Pulmonary Function in Ataxia-Telangiectasia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets