B cell clones, either malignant or benign, normally produce high amounts of monoclonal immunoglobulins (paraproteins). Paraproteins are made up of intact immunoglobulins, single light chains (Free Ig Light Chains – FLC), or more rarely, single heavy chains. The Free Ig Light Chains, kappa or lambda, have been considered for a long time as a byproduct of plasma cells but recent published data indicate that FLCs may account for some specific functions during immune response. Indeed a new disease entity termed light chain MGUS was defined: an abnormal free light chain ratio (FLCR) has proven to be predictive for progression of MGUS, solitary plasmacytoma of bone, amyloidosis, multiple myeloma (MM), Waldenstrom’s macroglobulinemia, and smoldering MM. Furthermore, a subset of monoclonal FLCs possesses intrinsic pathogenicity being a trigger factor of diseases such as AL amyloidosis or light chain deposition disease (LCDD). In the present study we combine different FLCs purification protocols and LC-MS/MS analysis to identify binding partners that associate with the light chains in the blood stream (FLCs interactome). We decided to compare MGUS and MM patients with Healthy donors. 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. In our study we characterized directly in LC-MS/MS different proteins associated with the FLCs with respect to their different patient origin.

Characterization of Immunoglobulin Free Light Chains Interactome

DI NOTO, Giuseppe;PAOLINI, Lucia;CAIMI, Luigi;RICOTTA, Doris
2012

Abstract

B cell clones, either malignant or benign, normally produce high amounts of monoclonal immunoglobulins (paraproteins). Paraproteins are made up of intact immunoglobulins, single light chains (Free Ig Light Chains – FLC), or more rarely, single heavy chains. The Free Ig Light Chains, kappa or lambda, have been considered for a long time as a byproduct of plasma cells but recent published data indicate that FLCs may account for some specific functions during immune response. Indeed a new disease entity termed light chain MGUS was defined: an abnormal free light chain ratio (FLCR) has proven to be predictive for progression of MGUS, solitary plasmacytoma of bone, amyloidosis, multiple myeloma (MM), Waldenstrom’s macroglobulinemia, and smoldering MM. Furthermore, a subset of monoclonal FLCs possesses intrinsic pathogenicity being a trigger factor of diseases such as AL amyloidosis or light chain deposition disease (LCDD). In the present study we combine different FLCs purification protocols and LC-MS/MS analysis to identify binding partners that associate with the light chains in the blood stream (FLCs interactome). We decided to compare MGUS and MM patients with Healthy donors. 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. In our study we characterized directly in LC-MS/MS different proteins associated with the FLCs with respect to their different patient origin.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11379/237912
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