>>Proteomics. 2003 Jun;3(6):957-61.
Analysis of complex autoantibody repertoires by surface-enhanced laser desorption/ionization-time of flight mass spectrometry.
Grus FH, Joachim SC, Pfeiffer N.
Department of Ophthalmology, University of Mainz, Mainz, Germany.
Normal sera contain a large number of naturally occurring autoantibodies which can mask important disease-associated ones. Western blotting has evolved as the most important tool to demonstrate autoantibodies in autoimmune diseases, because of its ability to simultaneous screening for a wide spectrum of different antigens. In previous studies we have shown the diagnostic potential of the analysis of autoantibodies in autoimmune diseases by means of multivariate statistics and artificial neural networks. However, the Western blotting procedure remains very time-consuming and is also limited in sensitivity. Therefore, we used an on-chip approach for the analysis of autoantibodies. This ProteinChip system uses ProteinChip arrays and SELDI-TOF MS (surface-enhanced laser desorption/ionization-time of flight mass spectrometry) technology for capturing, detection, and analysis of proteins without labelling or without the need of chemical modification. The microscale design of the arrays allows the analysis of very small quantities of proteins. In the present study, we used arrays with biologically activated surfaces that permit antibody capture studies. Protein-A-Chips were incubated with sera of patients (n = 12). After washing, the chips were incubated with a complex solution of autoantigens and subsequently washed again. If the Protein-A bound autoantibodies recognized their antigens, these proteins could be separated by their molecular masses and were to be detected by mass spectrometry. Previous studies using monoclonal antibodies have demonstrated that the detection limit is in the attomole level. Furthermore, all sera were analyzed by conventional Western blotting for direct comparison. In the present study, we have shown complex on-chip antibody-antigen reactions. At higher molecular weights (> 30 kDa) the detection sensitivity of this on-chip method was comparable to conventional Western blotting. At lower molecular mass, the Western blot technique is easily exceeded by the on-chip method. Considering that this on-chip procedure is quite easy to use, is much less time-consuming than Western blotting, and is much more sensitive at least in the low molecular weight range, the SELDI-TOF technology is a very promising approach for the screening of autoantibodies in autoimmune diseases. Due to its versatility, this on-chip technology could allow the large-scale screening for complex autoantibody distributions for diagnostic purposes and early detection of autoimmune diseases might be possible.<<
This is the first publication I've seen pointing to the use of Ciphergen equipment to establish diagnostics for autoimmune disease. It also notes the superiority over Western blotting, and we recently saw some pharma scientists comparing it favorably to gel electropheresis. Signs that acceptance in the bench scientist community continues to build, IMO.
Peter, I too, am looking forward to their articulating their business plan in commercializing diagnostics. Other parts of the plan seem pretty clear. With the litigation out of the way, they may also talk more about the biomarker centers and deals related to them. Though they've been fairly forthcoming about that despite legal overhang.
Supposedly, they were going to choose the two most promising indications and move on those. We could probably make an educated guess as to what those will be by looking at 1) the funding, since they get rights to markers developed by collaborators they fund, such as the Hopkins and East Virginia Med School teams, 2) the size of the market, 3) the relative performance of their biomarker patterns versus the gold standard, and 4) the clinical meaningfulness of screening/early detection in the given indication.
I would further guess that they would let a third party like Biosite do the manufacturing and marketing, and simply collect royalties. Ciphergen contends that there is plenty of market left to penetrate in terms of selling their machines and chips. Their recent performance in a market that has been tough for the last couple of years augurs well. It's a razor/razor blade model, of course, but you knew that.
I'm wondering if a PR blast will come with the AACR meeting, which starts next week, if memory serves. Might go sniff around in the late breaking abstracts section . . . Anyhow, a spike related to developments presented there might tempt me to take some off the table until they say something concrete about commercializing diagnostic tests.
Cheers, Tuck |
