The previous edition summarised data from many observational studies reporting elevated polyclonal sFLCs in association with various diseases. Subsequently, in 2012, Dispenzieri et al.  published data from follow-up of over 15000 people seen at the Mayo Clinic in Rochester, Minnesota, USA. After removal of all subjects with an abnormal sFLC ratio or other evidence of a monoclonal process, there was a significant association between elevated polyclonal sFLC concentrations and early mortality (Section 35.10). These findings have been corroborated in two further, independent, populations by Eisele et al.  and Anandram et al. . The risk associated with elevated sFLC was found to be independent of other markers of renal function, inflammation or acute-phase response but the early mortality was attributable to multiple causes, indicating no obvious path for clinical intervention. This remains an area of active research.