Analysis of gamma-globulin mobility on routine clinical CE equipment: exploring its molecular basis and potential clinical utility.
A study was conducted on the variability of gamma-globulin mobility in serum protein electrophoresis and its molecular basis. We found that the migration time of gamma-globulins can be reproducibly determined (CV=1.1%) on clinical CE equipment. Moreover, we found a significant difference (p<0.001) in the migration of gamma-globulins between chronic liver disease patients (n=98) and a healthy reference group (n=47). Serum immunoglobulins were purified from these patients' sera using protein L-agarose and their glycosylation was studied using CE on a DNA sequencer. This glycomics approach revealed that several non-sialylated N-glycans show a moderate Pearson correlation coefficient (r=0.2-0.4) with the migration time of gamma-globulins. Their sialylated structures correlate negatively (r=-0.2 to -0.3). Immunoglobulins are significantly more sialylated in the healthy reference group compared with the patients (p<0.001). We estimated that sialylation heterogeneity contributes about 36% to the molecular variance (carbohydrates and amino acid composition) that affects the electrophoretic mobility of immunoglobulins. This is the first report on the migration time of gamma-globulins on a clinical CE instrument and its potential clinical value to the routinely analyzed serum protein CE profiles.
Vanderschaeghe
Dieter
D
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
Debruyne
Evi
E
Van Vlierberghe
Hans
H
Callewaert
Nico
N
Delanghe
Joris
J
D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D019075:Electrophoresis, Capillary / Q000379:methods*; D005260:Female; D006031:Glycosylation; D006801:Humans; D008107:Liver Diseases / Q000097:blood; D008297:Male; D018709:Statistics, Nonparametric; D005719:gamma-Globulins / Q000737:chemistry / Q000302:isolation & purification*
D015415:Biomarkers; D005719:gamma-Globulins