Clinical Conditions Associated with Elevated Serum Levels of Polyclonal Free Light Chains

Background: Polyclonal gammopathy with elevation of the intact immunoglobulin (Ig) molecules is a laboratory finding commonly observed in a variety of inflammatory disorders, such as infections, autoimmune diseases, and cancer. Little is known about the relative frequency of the conditions associated to the serum elevation of polyclonal free light chains (FLCs). Methods: We reviewed laboratory data and clinical features of 62 patients who were referred to our Hematology/Oncology clinic due to elevated Ig or serum FLCs, and for whom the work-up ruled out the presence of a clonal plasma cell dyscrasia or a hematologic malignancy. Results: Serum elevation of the polyclonal intact Ig, FLCs, or both, was observed in 8 (13%), 30 (48%), and 24 (39%) patients, respectively. The causes of elevated Ig, either alone or in combination with elevated FLCs, were connective tissue diseases (12 cases), autoimmune diseases (6 cases), infections (5 cases), and various other chronic diseases (10 cases). Among the 30 patients with isolated elevation of FLCs, an inflammatory disease was present in 5 cases, and 22 patients (73%) had either acute or chronic kidney disease. In these patients, we found a correlation between FLC level and glomerular filtration rate (GFR): r was −0.61 ( P = 0.003) and −0.49 ( P = 0.021) for kappa and lambda FLCs, respectively. Conclusion: Serum elevation of polyclonal FLCs can be due to either overproduction, associated with various infectious and inflammatory disorders, or underexcretion, related to chronic renal insufficiency. We believe that a term such as polyclonal lightchainemia could be used to indicate the laboratory finding of elevated FLCs in the absence of a clonal hematologic dyscrasia. This should be distinguished from the traditional terms hypergammaglobulinemia and polyclonal gammopathy, which instead refer to the elevation of all Ig molecules.