Proteomics in human disease: Cancer, heart and infectious diseases

In recent years, genomics has increased the understanding of many diseases. Proteomics is a rapidly growing research area that encompasses both geneti c and environmental factors. The protein composition represents the functio nal status of a biological compartment. The five approaches presented here resulted in the detection of disease-associated proteins. Calgranulin B was upregulated in colorectal cancer, and hepatoma-derived aldose reductase-li ke protein was reexpressed in a rat model during hepatocarcinogenesis. In t hese two investigations, attention was focused on one protein, obviously di ffering in amount, directly after two-dimensional electrophoresis (2-DE). A dditional methods, such as enzyme activity measurements and immunohistochem istry, confirmed the disease association of the two candidates resulting fr om 2-DE subtractive analysis. The following three investigations take advan tage of the holistic potential of the 2-DE approach. The comparison of 2-DE patterns from dilated cardiomyopathy patients with those of controls revea led 25 statistically significant intensity differences, from which 12 were identified by amino acid analysis, Edman degradation or matrix-assisted las er desorption/ionization-mass spectrometry (MALDI-MS). A human myocardial 2 -DE database was constructed, containing 3300 protein spots and 150 identif ied protein species. The number of identified proteins was limited by the c apacity of our group, rather than by the principle of feasibility. Another field where proteomics proves to be a valuable tool in identifying proteins of importance for diagnosis is proteome analysis of pathogenic microorgani sms such as Borrelia burgdorferi (Lyme disease) and Toxoplasma gondii (toxo plasmosis). Sera from patients with early or late symptoms of Lyme borrelio sis contained antibodies of various classes against about 80 antigens each, containing the already described antigens OspA, B and C, flagellin, p83/10 0, and p39. Similarly, antibody reactivity to seven different marker antige ns of T. gondii allowed differentiation between acute and latent toxoplasmo sis, an important diagnostic tool in both pregnancy and immunosuppressed pa tients.