People with Job’s Syndrome Have Impaired Immune Memory

A research team at the National Institute of Allergy and Infectious Diseases (NIAID) has found that people with Job’s syndrome (also known as autosomal-dominant hyper-immunoglobulin E syndrome) have a lower number of immune memory cells, which makes them more susceptible to viral reactivation. The findings, which appear in the Nov. 23, 2011, issue of Immunity, provide a potential treatment strategy for people with Job’s syndrome, as well as offer clues about how immune cells in healthy people control chronic viral infections.

The NIAID team examined patients with Job’s syndrome to better understand how immune memory develops. Job’s syndrome is a condition caused by a mutation in a gene for the protein STAT3, which aids in the development and specialization of specific types of immune memory T cells. The team observed that, when compared with healthy people, patients with Job’s syndrome lack a major population of circulating memory T cells, which are thought to be a source for long-term T cell memory. These low numbers of central memory T cells are closely associated with these patients’ increased susceptibility to varicella zoster virus reactivation, causing them to have a significantly higher chance of developing shingles at a young age (less than 50 years old) and of experiencing repeated episodes of shingles compared with healthy people. What’s unique about this finding is that people with Job’s syndrome do not typically experience severe chicken pox or have difficulty clearing the initial infection. This means that Job’s syndrome is one of the few diseases that predisposes patients to developing shingles, but it does not affect their response to chicken pox.

Based on these findings, the researchers concluded that measuring circulating central memory T cells, or STAT3 function, could be a way to identify someone who is at greater risk for developing shingles or could benefit from the shingles vaccine. In addition, new therapeutics that boost the activity of STAT3 also could help protect people from VZV reactivation. Further study is needed, they said, to determine if young, otherwise healthy people who experience episodes of shingles have impaired memory T cells. In addition, more research is needed to better understand what level of immune memory is needed to protect people who have received the chicken pox vaccine from developing shingles.