A 5-year-old boy has a history of recurrent pneumococcal pneumonia, Pneumocystis carinii pneumonia (PCP), and bacterial ear infections. His maternal uncle and an older brother experienced the same symptoms, but he has an older sister who is healthy. Laboratory studies indicate normal numbers of B cells and T cells, and the serum contains mostly IgM and very little IgG. Which of the following abnormalities would NOT be likely in this patient?

Question

Quizplus · Accepted Answer

This is a common presentation of hyper-IgM syndrome. Patients with this disease have B cells that are unable to undergo isotype switching, and therefore contain only IgM in the serum but very low levels of IgG, IgA, and IgE. Clinically, these patients are susceptible to bacterial infections and often present with a history of recurrent pneumonia, otitis media, and gastrointestinal infections. Mutations in genes coding for CD40L, CD40, and activation-induced deaminase (AID) have been identified in these patients. During an immune response, T cell interactions with B cells via CD40L-CD40, as well as active AID, are both essential for numerous processes, including isotype switching, somatic mutation, and germinal center formation. Thus, patients with hyper-IgM syndrome produce antibodies that typically have a lower affinity for antigen (due to the lack of somatic mutation) and do not develop large follicles containing a light zone and dark zone (germinal center) within lymph nodes. Mechanisms of generation of diversity of the Ig repertoire should not be impaired in this patient. Although somatic mutation of variable regions will be impaired, this will not be manifest in IgM antibodies. In addition, patients with either CD40L or CD40 mutations, but not AID mutations, will have an increased susceptibility to certain intracellular infections (such as Pneumocystic carinii pneumonia), because the microbicidal activity of macrophages is partially dependent on CD40-mediated signals.

A 5-Year-Old Boy Has a History of Recurrent Pneumococcal Pneumonia