susceptibility to infections in ataxia telangiectasia

Conditions: Ataxia Telangiectasia; Infections; Immunodeficiency; Lung Disease

Summary: death in ataxia telangiectasia (a-t) is usually due to cancer or chronic lung failure around 20 years of age. despite low lymphocyte counts (cd3, cd4, cd8 and cd19), iga and igg subclass deficiency opportunistic and acute severe respiratory infections are rare. the prevailing wisdom is that an immunoglobulin replacement therapy is not necessary in most of the patients. however no placebo controlled trials have been performed so far. the aim of this trial was to investigate the prevalence of mild and severe respiratory infections and / or chronic cough in classical a-t patients compared to healthy controls.

ataxia telangiectasia is an autosomal recessive multisystem disorder which is characterized by a progressive ataxia, conjunctival telangiectasia, a humoral and cellular immunodeficiency, an increased radiosensitivity and an increased risk for cancer (boder e, pediatrics, 1957). most patients die in their 2nd or 3rd decade of life due to a respiratory failure caused by progressive (interstitial) lung disease or due to malignancies (schroeder sa, pediatr pulmonol, 2010). in 1995 the sequence of the mutated at gene (atm) on chromosome 11q22-23 was identified. main problems besides the progressive neurodegeneration are recurrent infections of upper and lower respiratory tract and a growth retardation and malnutrition. these problems are caused by a mutation in the atm gene on chromosome 11, which encodes for a protein with several key functions in control of cell cycle and apoptosis (savitsky k et al., hum mol gen, 1995). several works already showed that patients with at have a variable immunodeficiency which is characterized by low lymphocyte counts, a lack of immunoglobulin a (iga), immunoglobulin g subclasses (igg2 and 4) and specific pneumococcal antibodies (schubert r, clin exp immunol, 2002). the course of disease is dependent on the at mutation respectively the residual kinase activity of atm which is found in about 10% of a-t patients. these patients are described as 'variant ats´ and have a better prognosis regarding immunodeficiency, susceptibility to infections and a possible growth retardation and malnutrition (verhagen m, hum mutat, 2012). despite the evidence for a humoral immunodeficiency a treatment with polyvalent immunoglobulins (igg) is not practiced in generally. in the 'clinical workshop on ataxia teleangiectasia´, that took place in frankfurt in january 2011, the investigators found out that the percentage of a-t patient, that are supplemented with immunoglobulins was only 10% to 60% depending on the different clinical centres.the goethe university childrens hospital in frankfurt, the biggest a-t centre in germany, takes care for more than 40 a-t patients. at the moment about 15% of these patients are treated with immunoglobulins. some observations show that the progress of the chronic lung disease cannot be prevented the usage of immunoglobulins. by now it´s not clear in what way patients suffer from an increased susceptibility to infections and if a substitution with immunoglobulins is needed. the aim of this trial is to investigate the incidence, intensity and duration of infections in patients with a-t compared to age matched healthy controls.

Eligibility criteria:
inclusion criteria: * a-t: clinically and/or genetically diagnosed a-t * no igg treatment from the point of being included into the study * healthy controls: healthy children or adults matched for gender and age * age 2 - 45 years * written informed consent exclusion criteria: * age \ 45 years * patient has to be treated with igg-replacement regularly * other diseases with influence on the immune system (e.g. diabetes mellitus, malignancy, dialysis-dependent renal failure)