We present a simple method for subclass typing of IgG paraproteins, wi
th which we have demonstrated a large number of paraproteins that were
undetected by conventional immunofixation techniques. The types and d
istribution of IgG subclass paraproteins were analyzed in 92 human ser
a in which IgG paraproteins had been demonstrated. The IgG subclass pa
raproteins were separated by agarose gel electrophoresis rapidly and s
imply and then typed with the use of sheep anti-human monospecific IgG
1-IgG4 antibodies. In 24 of the sera analyzed, IgG subclass typing rev
ealed 25 additional monoclonal bands that were not detected by convent
ional immunofixation electrophoresis with anti-IgG antisera. Most of t
hese belonged to a different subclass type. The overall subclass frequ
encies were 68% IgG1, 13% IgG2, 16% IgG3, and 3% IgG4. The distributio
n of paraprotein subclasses, however, was different in monoclonal gamm
opathies of undetermined significance in which more IgG3 was shown, wh
ereas in non-Hodgkin lymphomas the number of IgG2 paraproteins was gre
ater than expected; this finding may have diagnostic and prognostic si
gnificance.