Biological role of immunoglobulin Free light chains interactomes

Background. Monoclonal Gammopathy of Undetermined
Significance (MGUS) is a plasma cell disorder that could
be diagnosed incidentally and behave like a benign,
asymptomatic entity or progress (1% per year) to different
haematologic malignancies such as multiple myeloma
(MM). Monoclonal plasma cells often secrete high
amounts of immunoglobulin free light chains (FLCs) that
could induce tissue damage. Recently we showed (Di
Noto et al., 2013) that FLCs are internalized in endothelial
and myocardial cell lines and secreted in extracellular
vesicles (EVs). Our data show that MM EVs internalization
is FLCs and GAGs mediated and we could demonstrate
that MM EVs induce NfkB nuclear translocation.
Blocking FLCs with anti FLCs antibodies or masking the
GAGs recognition with heparin altered the EVs intracellular
uptake and NfkB nuclear translocation (Di Noto et al.,
2014). EVs carry determinant information about the onset
of MGUS-MM switching which can be exploited for early
assessment of MM onset and progression. Objectives. We
aim to identify binding partners that associate with the
FLCs in the blood stream (FLCs interactome) and are
involved in the EVs generation and cellular uptake.
Methods. EVs, purified from serum of control, MGUS and
MM patients, were analyzed by a blend of conventional
analytical techniques, MALDI TOF analysis and surface
plasmon resonance (SPR). Results and Conclusions. In a
previous proteomic study immuno-purified FLCs isolated
from patients with monoclonal gammopathies were characterised
and some proteins such as clusterin and albumin
associated with FLCs were identified. We then tracked the
binding isotherms of EVs to a heparin-coated sensorchips.
The results show a marked difference between the binding
isotherms of EVs from healthy individuals and from MM
and MGUS patients.