Flow Cytometric Diagnosis of X-Linked Hyper-IgM Syndrome: Application of an Accurate and Convenient Procedure

Hyper-IgM (HIM) syndrome encompasses a family of congenital immunodeficiency states characterized by frequent infections and markedly low serum levels of IgG, IgA, and IgE but normal or elevated levels of IgM. Many patients have neutropenia. The major defect shared by all forms of HIM syndrome is a failure of immunoglobulin isotype-switching. Recently, a flow cytometric assay was described in the immunology literature for diagnosis of patients with inherited X-linked (X-HIM) syndrome. Using this assay, activated CD4 peripheral blood T lymphocytes from two patients suspected of having HIM syndrome, and from their mothers, were subjected to immunofluorescent flow cytometric analysis for the expression of CD40 ligand (CD154 antigen). Test results established the diagnosis of X-HIM syndrome that was inherited in one patient and spontaneous in the other. The authors' experience illustrates that the flow cytometric assay used and described in detail here can facilitate an accurate and timely diagnosis of X-HIM syndrome. Because the assay can be carried out in most clinical flow cytometry facilities, it lends itself to use by pediatric hematologists in the standard evaluation of patients whose differential diagnosis includes that disorder. The authors hope this report will raise awareness of the value of this procedure.