The clinical significance of complete class switching defect in Ataxia telangiectasia patients

Abstract

Background: Ataxia telangiectasia (AT) is a primary immunodeficiency associated with recurrent infections. We aimed to investigate clinical and immunological classification in AT patients who suffer from a different spectrum of humoral immune defects.

Methods: AT patients were categorized according to the ability of class switching and patients with hyper IgM (HIgM) profile were defined as class switching defect (CSD).

Results: Serum immunoglobulin profile in 66 AT patients showed normal immunoglobulin level (22.8%), IgA deficiency (37.9%) and hypogammaglobulinemia (18.1%) in the majority of patients, while 21.2% had HIgM profile revealing CSD. CSD does not affect the frequency of infections, however, the frequency of lymphoproliferation (p < 0.001), and autoimmunity (p = 0.004) were significantly higher in this group. Neurologic symptoms in CSD patients are mild or appear after recurrent infections, therefore these patients were usually misdiagnosed as HIgM syndrome.

Conclusions: Although most of AT patients have reduced IgA levels or normal immunoglobulin levels, but a fraction of these patients may show CSD ensuing HIgM-profile. CSD poses affected individuals at higher risk of non-infectious complications.

Keywords: Ataxia telangiectasia; IgA deficiency; class switching defect; humoral immune defects; hyper IgM syndrome; hypogammaglobulinemia; immune deficiency; infection.