S. Ozaki et al., PREFERENTIAL EXPRESSION OF HUMAN LAMBDA-LIGHT-CHAIN VARIABLE-REGION SUBGROUPS IN MULTIPLE-MYELOMA, AL AMYLOIDOSIS, AND WALDENSTROMS MACROGLOBULINEMIA, Clinical immunology and immunopathology, 71(2), 1994, pp. 183-189
We have compared the distribution of lambda-light-chain variable-regio
n (V-lambda) subgroups among Ig lambda molecules found in the serum of
normal individuals with that of monoclonal Ig lambda components obtai
ned from patients with plasma cell and related immunoproliferative dis
orders. A panel of monoclonal antibodies specific for each of the majo
r human V-lambda subgroups-V-lambda I, V-lambda II, V-lambda III, V-la
mbda IV, VlambdaVI, and V-lambda VIII-was used in a highly sensitive e
nzyme-linked immunosorbent assay (ELISA) to quantitate each of these p
opulations. The mean distribution of Ig lambda I, Ig lambda II, Ig lam
bda III, Ig lambda IV, Ig lambda VI, and Ig lambda VIII molecules in s
erum specimens collected from 20 normal adults was similar to 40, 3, 4
3, 5, 5, and 3% of the total Ig lambda population, respectively. In co
ntrast, that of monoclonal IgG, IgA, and IgD proteins and Bence Jones
proteins obtained from patients with multiple myeloma and related gamm
opathies (n = 196) was similar to 27, 28, 39, 5, 0, and 1%, respective
ly. The percentage of monoclonal Ig lambda II components found in indi
viduals with AL lambda amyloidosis (n = 41) was comparably increased t
o that seen in multiple myeloma and was even higher in patients with W
aldenstrom's macroglobulinemia (n = 16), in whom 63% of the IgM lambda
proteins were of the V-lambda II subgroup. Also evidenced were differ
ences in the distribution of other V-lambda subgroups in the disease s
tates: Most striking was the predominance (41%) of the V-lambda VI sub
group among monoclonal lambda chains obtained from patients with AL am
yloidosis and that this subgroup was found exclusively on amyloidosis-
associated proteins. No Ig lambda VI-type myeloma- or macroglobulinemi
a-related proteins were identified. The observed alterations in V lamb
da subgroup distribution among ''pathologic'' monoclonal Igs were attr
ibuted to the particular disease and not related to the heavy-chain cl
ass. Our finding that certain V-lambda subgroups are nonstochastically
expressed in lambda-type multiple myeloma, AL amyloidosis, and Walden
strom's macroglobulinemia provides evidence for abnormal V-L gene usag
e in these disorders and, thus, furnishes new insight into their patho
genesis. (C) 1994 Academic Press, Inc.