Jadranka Kelečić

A contiguous deletion syndrome of X‐linked agammaglobulinemia and sensorineural deafness

Hearing loss in patients with X‐linked agammaglobulinemia is often attributed to recurrent infections. However, recent genetic studies suggest a different etiology in some patients. We present three unrelated patients, 6, 9, and 14 years of age, with large deletions of the terminal portion of the Bruton tyrosine kinase (Btk) gene extending 4.2–19 kb beyond the 3′ end of the gene. The DNA immediately downstream of the 3′ end of Btk contains the deafness‐dystonia protein gene (DDP). Mutations in this gene have recently been shown to underlie the Mohr–Tranebjaerg syndrome, which is characterized by sensorineural deafness, dystonia, and mental deficiency. Besides the immunodeficiency, our patients exhibited progressive sensorineural deafness. The clue to an associated hearing problem was delayed development of speech in one patient and post‐lingual deafness noticed between the age of 3–4 years in the other two. These patients have not yet exhibited significant associated neurologic deficits.

Expression of chemokine receptor CX3CR1 in infants with respiratory syncytial virus bronchiolitis

Respiratory syncytial virus (RSV) glycoprotein G mimics fractalkine, a CX3C chemokine, which mediates chemotaxis of leukocytes expressing its receptor, CX3CR1. The aim of this study was to examine the relationship between RSV infection and expression of perforin and IFN‐γ in CX3CR1‐expressing peripheral blood CD8+ T cells. Samples were collected from infants with RSV bronchiolitis, both in the acute and convalescence phase (n = 12), and from their age‐ and sex‐matched healthy controls (n = 15). Perforin expression and IFN‐γ secretion in CX3CR1+ CD8+ T cells were assessed by four‐color flow cytometry. The NF‐κB p50 and p65 subunit levels were also determined as markers of RSV‐induced inflammation. Study results showed perforin and CX3CR1 expression to be significantly lower in the convalescent phase of infected infants than in healthy controls. There was no significant difference in IFN‐γ secretion and NF‐κB binding activity between two time‐points in RSV‐infected infants, or when compared with healthy controls. Infants with prolonged wheezing had lower acute‐phase CX3CR1 levels in peripheral blood. These data indicate existence of an event persisting after acute RSV infection that is able to modulate effector functions of cytotoxic T cells, and also link disease severity with CX3CR1 expression.