Cover Picture: Proteomics – Clinical Applications 4/2008

AbstractIn this issue of Proteomics you will find the following highlighted articles:MALDI and methyl groups take on lysosomal storage disease diagnosisLysosomal storage disorders (LSD) result from the absence or loss of any of a wide variety of glycan‐processing enzymes that lead to accumulation of incompletely processed glyco‐molecules in lysosomes. Diagnosis of the particular type of LSD requires identification of the accumulated species, usually from urine. LSD diagnosis has been a target for many years, including use of GC/MS, TLC, NMR, HPLC, FACE and other techniques. Faid et al. take a simple approach that is quite successful and much less time consuming. After permethylating crude urine, a sample is first run on GC/MS to look for free sialic acid, an indicator of one set of diseases, then a cleaned up sample (C1–8) is analyzed by MALDI/TOF to characterize glycoproteins and glycopeptides present. The glycans were further analyzed by sequential exoglucosidase digestion on the MALDI target. Sulfated glycocompound analysis requires a desulfation step prior to permethylation.Faid, V. et al., Proteomics Clin. Appl. 2008, 2, 528–542.Popular prostate problem receives piercing lookProstate cancer (PCa) is one of the most frequent male cancers. It is also one of the most frequently misdiagnosed cancers. Prostate specific antigen (PSA) has improved the accuracy somewhat but still generates 700 000 false positives requiring biopsies per year in the US. And very low PSA levels don’t assure freedom from PCa. In short, there is no good biomarker for PCa. Theodorescu et al. recognized that anything recovered from blood had a good chance of being at least partially degraded so they looked at first void urine as a more likely source of stable material. Applying capillary electrophoresis coupled to TOF‐MS, the authors developed an “informative” panel of eight peptides that distinguished between first void and mid‐stream samples and a PCa‐specific panel of 12 proteins that detected the disease. Incorporating the 12 proteins with age and free PSA, sensitivity was 91%, specificity 69%.Theodorescu, D. et al., Proteomics Clin. Appl. 2008, 2, 556–570.No candy in candidiasisCandida albicans is a unicellular yeast that is the third most common nosocomial agent in ICU’s, costing ∼US$ 40 000 per incident. Early diagnosis of systemic candidiasis (SC) is crucial for successful control of the infection by antifungal therapies. Blood cultures are not fast and tissue biopsies are not sensitive but are the current “gold standards.” Pitarch et al. report here a serum protein marker for SC: anti‐Candida enolase (Eno1p) IgG. Comparing healthy with SC patients for antibodies against Candida cytoplasmic antigens, 15 antigens were recognized by the SC patients. The strongest response was to Eno1p which was the only antigen to produce a response in all 12 patients. The IgG was tested for its suitability as an antigen in Western and capture ELISA tests. Although the tests appear reliable for detecting SC, they were not good for prognosis. A considerable amount of work remains for full qualification of the test.Pitarch, A. et al., Proteomics Clin. Appl. 2008, 2, 596–618.