Cover Picture: Proteomics – Clinical Applications 7/09

AbstractProteome of a chromatography columnRheumatoid arthritis is miserable for those who have it. An autoimmune disorder, about 1% of the population is affected, apparently due to a combination of environmental and genetic factors. A substantial sample of the immune system — T‐cells, B‐cells, antigen presenting cells, synovial cells and others — is activated during the chronic phase. One therapy, developed fairly recently, is immuneadsorption apherisis using a column containing a matrix coated with staphylococcal protein A. There are side effects to the treatment so (drum roll, please), proteomics to the rescue. Kienbaum et al. ask “Just what does stick to that column?” Applying 1‐D and 2‐D gel electrophoresis and MALDI‐TOF MS, they find about 500 spots are eluted and evidence of complement involvement. Likely in situ generation of anaphylatoxin C3a is another bullet to dodge during therapy.Kienbaum, M. et al., Proteomics Clin. Appl. 2009, 3, 797–809.BYO salivary protease and inhibitorsSaliva: what is it? Is it just a fluid, like urine or a fluid tissue, like blood, or… In any case, it is a broad but somewhat obscured window on the state of health of the body. Saliva includes a wide variety of enzymes, including proteases and collagenases, which must be regulated to maintain oral health. Many of these have not been identified by MS methods, so Sun et al. took on the task. Their principal tool is zymography, using human histatins, a group of small non‐glycosylated salivary peptides, as substrates, followed by LC‐ESI‐MS/MS. Their work confirmed the identifications made by classical methods of detection for several proteases and (surprise) protease inhibitors. Unexpected were finding both proteases and inhibitors in multi‐band clusters on the zymograms. Whether these are true complexes or coincidences must be looked at carefully.Sun, X. et al., Proteomics Clin. Appl. 2009, 3, 810–820.Topers' MALDI‐TOF/TOF scores reveal more magneticallyCurrently available enzymatic biomarkers for alcohol abuse have several shortcomings that tend to underreport the extent of a patient's problem. As many as 25% of problem drinkers have normal scores for the gamma glutamyltransferase (GGT) test. A CDT test requires that daily alcohol intake be above a minimum to register. Sogawa et al. report here on a 16‐patient trial of a commercially available serum analysis test that uses magnetic beads for sample handling and recovery. The new system is more sensitive and more flexible than the test that was used previously but is less expensive and revealed more than 20 new peaks that had significant shifts in volume with abstinence. Some of the fragments could capture the “normal” GGT patients. A multi‐center trial is being planned.Sogawa, K. et al., Proteomics Clin. Appl. 2009, 3, 821–828.