Cell Biochemistry Martinsried
Human Disease

G.Valet

Potential of Cytometry

1. General Considerations:

Diseases are caused by biochemical changes in cellular systems or organs. The analysis of such changes should provide information on individual patient disease diagnosis and prognosis as well as on therapeutic efficiency.

The prediction of individual patient disease prognosis is of high clinical interest but practically impossible in most instances by the traditional biochemical analysis of body fluids as well as by other clinical or histo- and cytopathological analyses.

A major reason for this is that the results of humoral biochemistry measurements reflect cell biochemical disease processes only indirectly. Cell derived biomolecules may not appear outside cells, they may be metabolically altered or remain undetectable due to their high dilution in the body's fluid compartments. The results of biochemical measurements on organ tissue preparations as an alternative are difficult to interpret because organs contain a variety of discrete cell types whith potentially different reactivities to disease processes.

The combination of microscopic single cell observation with the simultaneous multiparameter biochemical cell analysis represents the important advantage of cytometry for disease detection and monitoring.

2. Potential of Cytometry

Patterns of various biomolecules can be reliably quantitated by cytometric analysis of viable or fixed cells following staining with biochemically specific fluorescent dyes. The particular effort of this laboratory consists in the development of specific stains for cell functions in viable cells as sensitive indicators of the altered cellular metabolism in disease. The simultaneous multiparameter data collection by the cytometer provides high amounts of functional and structural information on heterogeneous i.e. essentially unprocessed ex-vivo cell suspensions shortly after removal from the human body.

Unlike tissue biochemistry, the cellular heterogeneity of human samples offers important advantages for clinical and experimental cytometry because of the high information content of simultaneously collected multiparameter data from a great variety of different cell types.

3. Individual Patient Prognosis by Standardized Multiparameter Data Classification (SMDC)

The exhaustive extraction of information from cytometric or clinical chemistry multiparameter measurements by a laboratory and instrument independent, self learning and standardized data classification algorithm, developed earlier (2) by this laboratory, provides single patient prognostic as well as diagnostic evaluations with unprecedented accuracy.

Clinical examples from several different medical disciplines underline this point.

The practical consequence of this approach is that complications in a number of common diseases like severe infections, shock, exacerbation of rheumatoid and asthmatic disease, thromboembolic complications in diabetes, myocardial infarction and stroke sensitive patients or survival in cancer patients may become predictable at the individual patient level by combined multiparameter cytometry and SMDC.

Minor interventions like cytometry supervised punctual antiphlogistic therapy e.g. shortly before the imminent exacerbation of rheumatoid disease may prevent severe tissue destruction leading otherwise to the stepwise disabling of the patient. The cell biochemical approach would have in this case the potential to significantly postpone the invalidization of patients. The higher quality of patients's life would be paralleled by shorter disease periods at substantially lower costs of therapy.