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Free light chains in plasma of patients with light chain amyloidosis and non‐amyloid light chain deposition disease. High proportion and heterogeneity of disulfide‐linked monoclonal free light chains as pathogenic features of amyloid disease
Author(s) -
Kaplan Batia,
RamirezAlvarado Marina,
Sikkink Laura,
Golderman Sicilia,
Dispenzieri Angela,
Livneh Avi,
Gallo Gloria
Publication year - 2009
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2008.07522.x
Subject(s) - immunoglobulin light chain , amyloidosis , al amyloidosis , chemistry , amyloid (mycology) , monoclonal , monoclonal antibody , biophysics , antibody , pathology , biology , medicine , immunology , inorganic chemistry
Summary Immunoglobulin light chain amyloidosis (AL) and non‐amyloid light chain deposition disease (NALCDD) are different forms of protein aggregation disorders accompanied by a monoclonal gammopathy. Monoclonal free light chains (FLCs) are precursors of the pathological light chain tissue deposits that are fibrillar in AL and granular in NALCDD. However, direct biochemical examination of plasma FLC precursors, which would allow comparison and better understanding of these two diseases, is still lacking. In this study, we examined FLCs in plasma of patients with AL and NALCDD by employing separation on Sep‐PaK C18 cartridges, micro‐preparative electrophoresis, Western blotting and mass spectrometry. Comparative analysis of AL versus NALCDD and control plasma samples showed new evidence of increased level and heterogeneity of circulating disulfide‐bound FLC species in AL. In addition to full length monomers comprising the disulfide‐linked FLCs, the monoclonal disulfide‐bound FLC fragments were typically revealed in AL plasma. We hypothesized that enhanced disulfide binding of FLCs in AL interferes with their normal clearance and metabolism, which in turn might play a role in amyloid formation. The applied methods might be useful to diagnose or predict the pathological form of the disease and shed light on the mechanisms involved in light chain aggregation in tissues.