Classification of malnutrition by statistical analysis of quantitative two-dimensional gel electrophoresis of plasma proteins.

An attempt to use the relative concentrations of major plasma proteins for clinical assessment of severe malnutrition is described. Quantitative two-dimensional gel electrophoresis was used to measure the concentrations of 24 major proteins in small aliquots of plasma obtained from children, aged 0 to 3 years, who were patients and outpatients in Liberian hospitals. Fifteen had a clinical diagnosis of kwashiorkor, 36 were diagnosed with marasmus, and 18 were controls. There were also 5 controls from the United States. The individuals were placed in six groups; kwashiorkor, kwashiorkor who died during treatment, marasmus, marasmus who died, Liberian controls, and U.S. controls. The amount of protein in each spot in the two-dimensional gels was estimated by measuring bound stain using a laser scanner and computerized image analysis. We found very low serum transferrin levels in malnourishment, in agreement with reports from other investigators. All of the data for 24 protein variables were pooled for factor analysis; the mean factor scores for each group differed, with the kwashiorkor groups furthest from the controls. Results of discriminant analysis using the amounts of different numbers of protein variables (3 to 24) were compared for posterior assignment of individuals to groups. The validity of the method was tested by analysis of plasma aliquots obtained from patients following initiation of therapy and which were not a part of the training set. Predictive performance (prognosis of patient survival) depended upon the number of protein variables used. Although artifactual fitting of the data is expected to contribute to performance as the number of variables is increased, use of as many as 7 variables may be justified, even with our small patient groups. Possible use of these results for development of a practical clinical test is discussed.