Internalization Pathway of Amyloidogenic Serum Free Light Chains

• “Internalization pathway of amiloydogenic Serum Free Light Chains” Ricotta D., Di Noto G., Dossi A., Paolini L., Radeghieri A., Amoroso B. and Caimi L. Poster communication at 6th International Symposium on Clinical Applications of Serum Free Light Chain Analysis (plus Hevylite). Bath, UK on 23rd and 24th September 2010 Primary (AL) Amyloidosis is a disease of protein misfolding. During plasma cell dyscrasia, such as micromolecular myeloma, plasma cells produce a great amount of monoclonal immunoglobulin free light chains (kappa or lambda FLCs) that may accumulate in different peripheral districts and determine tissue damages. It has been shown that FLCs induce oxidative stress and FLCs internalization in cardiac fibroblasts enhances sulfatation of secreted glycosaminoglycans (GAGs) suggesting that the intracellular trafficking pathway of FLCs could be correlated with the amiloydogenic potential of paraproteins. AIMS The mechanism of internalization and trafficking of FLCs is not well understood, so we aimed to characterize this pathway. METHODS In order to identify a correlation between the FLC phenotype and their pathogenicity, we have investigated the internalization rate of different lambda and kappa FLCs (belonging to hospitalized patients) in different cellular lines. Indeed, the mechanisms of internalization in different cellular subtypes might be an important key in the study of different pathological conditions strictly correlated to FLCs (systemic and not only kidney related) metabolism. RESULTS SUMMARY/CONCLUSION Our results highlight that the monoclonal FLCs of every patient behaves in a different way in different cellular lines and we could also show that not only epithelial cells are able to process paraproteins. Considering these data we could hypothesize that the interaction of FLCs with peripheral districts depends on high specific receptors expressed on certain cellular lines and/or that each patient has an individual clinical pattern due to the paraprotein molecular structure.