Focused Microarray Analysis of Peripheral Mononuclear Blood Cells from Churg-Strauss Syndrome Patients

DNA diagnostics are useful but are hampered by difficult ethicalissues. Moreover, it cannot provide enough information on theenvironmental factors that are important for pathogenesis ofcertain diseases. However, this is not a problem for RNA diagnostics,which evaluate the expression of the gene in question. We herereport a novel RNA diagnostics tool that can be employed withperipheral blood mononuclear cells (PBMCs). To establish thistool, we identified 290 genes that are highly expressed in normalPBMCs but not in TIG-1, a normal human fibroblast cell. Thesegenes were entitled PREP after predominantly expressed in PBMCand included 50 uncharacterized genes. We then conducted PREPgene-focused microarray analysis on PBMCs from seven cases ofChurg–Strauss syndrome (CSS), which is a small-vesselnecrotizing vasculitis. We found that PREP135 (coactosin-likeprotein), PREP77 (prosaposin), PREP191 (cathepsin D), PREP234(c-fgr), and PREP136 (lysozyme) were very highly up-regulatedin all seven CSS patients. Another 28 genes were also up-regulated,albeit more moderately, and three were down-regulated in allCSS patients. The nature of these up- and down-regulated genessuggest that the immune systems of the patients are activatedin response to invading microorganisms. These observations indicatethat focused microarray analysis of PBMCs may be a practical,useful, and low-cost bedside diagnostics tool.