Patient Vignette (part 1)
A Case of Mistaken Immunologic Identity?
In the evaluation of suspected primary immunodeficiency disorders, screening assays are particularly helpful to guide the diagnostic workup. This includes developing strategies for targeted (and cost-effective) genetic testing. In addition, these assays add relevance and significance to abnormal genetic analyses by linking the genotype of a particular genetic sequence variation (or variations) to the clinical and immunological phenotype. Examples of screening assays performed in our Laboratories include measurement of intracellular perforin and granzyme B for hemophagocytic disorders, detection of the gamma chain of the IL-2 receptor (CD132) on lymphocytes for X-linked SCID, amongst many others.
The figures on this page depict results of our CD40L (a.k.a. CD154) assay. This assay screens for the presence of the X-linked form of Hyper IgM syndrome (HIGM1). The basic immunological defect in HIGM1 concerns defective CD40L up-regulation on activated (CD4-expressing) T cells. The top two histograms represent two patient samples, while the bottom histogram shows a healthy control for comparison. The green lines correspond to CD40L expression on (CD4+) T cells at baseline, while the blue lines show up-regulation of CD40L after 5 hrs of polyclonal T-cell activation (numbers denote the percentage of gated T cells that express CD40L). The assay also measures upregulation of ICOS (see second Newsletter; Spring, 2006) and CD69 to ensure that lack of CD40L up-regulation is not the consequence of more global T-cell dysfunction.
Is this a case of mistaken Immunologic Identity? Click here for part 2 of the Patient Vignette.
