An Exercise in Pattern Recognition
The immune system depends on pattern recognition in order to detect danger signals and counteract infections. The diagnostic process of immunodeficiency disorders is largely based on pattern recognition as well. This can be relatively straightforward, such as observing absence of B cells in X-linked Agammaglobulinemia (XLA), but can also be considerably more challenging. Part of the design and execution of immunological assays at the DIL is focused on facilitating pattern recognition, and this includes looking at qualitative aspects of data, as well as evaluating data that is not part of the primary intention of the assay (i.e. the data that is not reported). At regular intervals, we will use the Newsletter to exercise our brains in pattern recognition. Have you discovered an interesting pattern? Share it with us and have it included in a future Newsletter. You can submit your suggestion(s) via e-mail at: immunodeficiencies@cchmc.org
1. Skewed CD4:CD8 ratio. An ALPS panel was obtained in a patient with thrombocytopenia. The figure represents a dotplot of CD4+ T cells (right upper quadrant) versus non- CD4+ T cells (left upper quadrant), which in this case corresponds to CD8+ T cells. The CD4:CD8 ratio is about 16:1. The patient was suspected of having Wiskott-Aldrich syndrome (WAS); the WASP (WAS Protein) assay performed at the same time confirmed this diagnosis. The pattern of skewed CD4:C8 ratios (albeit not always as extreme as in this case), associated with CD8+ T-cell lymphopenia is typical for WAS. Our only recently diagnosed WAS patient, from a series of about 10 patients, who did not reveal this pattern, was an infant with acute CMV infection (also highlighting the ever-present exceptions to a rule and the need to regard data in the context of clinical info).
2. CD21-negative B cells. Sometimes the observed patterns suggest who ordered a particular assay. The predominant population of CD21-negative B cells (figure on next page) is a relatively common pattern, observed in patients with Systemic Lupus Erythematosus (SLE). This is often accompanied with other interesting patterns, including reduced CD5+ B cells, B cells with bright expression of CD27 and the presence of plasma-blasts, defined on the basis of dim CD19 expression in combination with bright expression of CD38 and/or CD138. CD21-negative B cells are also observed as part of B-cell reconstitution following B-cell depletion by rituximab, but in that scenario, the accompanying pattern includes increased CD10+/CD5+ and CD27-negative B cells and no plasma-blasts (see also Spring-2006 and Spring-2007 Newsletters).
3. Bright CD3 expression. As is demonstrated by the top left dotplot, paying attention to qualitative aspects can be revealing. It shows a proportion of T cells expressing a higher level of CD3 fluorescence intensity (A). These cells express the gamma/delta Tcell receptor (TcR), indirectly determined by the lack of expression of the alpha/beta TcR. As discussed in the Fall-2007 Newsletter, gamma/delta T cells often lack CD4 and CD8 (B), and may show increased or decreased expression of other markers, such as HLA-DR and CD27 (C).
