Question

Case study

8-year old girl with recurrent infections caused by Streptococcus pyogenes and Hemophilus influenza was admitted to the hospital following a 5-day sinus infection. Her mother noted that she had developed a productive cough and high fever. Her white blood cell count was 3200/ul (normal count 5000-9000/ul). 25% percent of her white cells were neutrophils (very low), 40% were lymphocytes (normal), and 29% were monocytes (elevated, normal 2 to 8%). A serum test revealed that her IgG level was 35 mg/dl (normal 600-1500 mg/dl), IgA was undetectable (normal 150-225 mg/dl) and her IgM level was 210 mg/dl (normal 75-150 mg/dl). A flow cytometric analysis of her peripheral blood cells revealed that all of her B cells were IgM⁺, IgD⁺.

1. Provide a possible diagnostic for the patient.

Answer 1

Possible diagnosis for the condition described in the above mentioned question can be a Hyper IgM syndrome.

This possible diagnosis is based on the major fact that flow cytometric analysis showed that her her B cells were IgM+, IgD+. Along with this observation there was a pyogenic infection. There was elevated level of IgM and decreased level of other antibodies. up and down levels of other cells also supports the condition of Hyper IgM syndrome.Basically, there are many genetic defects that leads to hyper IgM syndrome. IgM is a very basic antibody produced by B cells. This production takes place initially before the mechanism of class switching which happens due to the exposure to pathogen recognized by the immune system. Active and mature B cells are very efficient in class switching to produce other antibodies required to fight with pathogens. In hyper IgM syndrome B cells keep producing IgM antibodies because of the defect in switching to other class of antibodies, which can be observed with higher levels of IgM and decreased level of other antibodies. possible explanation to this condition can be : T cells in our body expresses CD40L which has a tendency to interact with CD40 receptor on T cells which is also expressed by B cells in constitutive manner. This mechanism is somehow responsible for further functioning of B cells. In patients with hyper IgM syndrome there is a mutation in CD40L which affects its interaction with CD40 present on B cells and therefore further functioning of B cell in terms of antibody class switching is hampered. Reason behind patients of hyper IgM syndrome being susceptible to various infection specially pyogenic infection is the inefficiency of producing other class of antibodies required for specially IgG that are required to act against agents causing these infections. These explained mechanism supports all the symptoms and signs described in the question and hence it can be said that the girl is suffering from hyper IgM syndrome.