Free immunoglobulin light chains as a risk factor in renal and extrarenal complications

Immunoglobulin light chains (IgLCs) are part of intact immunoglobulins and contribute to antigen recognition. However, IgLCs are synthesized by B cells slightly in excess of Ig heavy chains and are found in the plasma of healthy people at low concentrations. IgLCs are metabolized primarily by the kidney. In B-cell lymphoproliferative disorders, e.g., multiple myeloma, the serum concentration of monoclonal IgLCs markedly increases and the reabsorptive capacity of the proximal tubuli is exceeded. As a consequence, monoclonal IgLCs appear as Bence Jones proteins (BJPs) in the urine and can give rise to IgLC deposits in the kidney that may result in renal insufficiency. In patients with chronic kidney disease (CKD) of various origins, reduced excretion leads to increased serum levels of polyclonal IgLCs. Free IgLCs interfere with essential functions of neutrophils, cells of the first-line nonspecific immune defense, and therefore contribute to the disturbed immune function in CKD patients. IgLCs attenuate the coordinated apoptotic cell death of neutrophils and therefore may interfere with the normal resolution of inflammation and contribute to the chronic inflammatory state found in CKD patients. Recently it was shown that IgLCs may confer mast cell-dependent hypersensitivity and thereby play an important role in the development of contact sensitivity.