Immunoglobulin free light chains are produced in excess during normal antibody synthesis. Their evaluation is commonly used in case of a monoclonal gammopathy. In polyclonal hypergammaglobulinemia related to the Sj？gren syndrome or systemic lupus, erythematosus serum free light chain levels are increased and could correlate with disease activity. We show here that the κ ( ) and λ ( ) free light chains and the κ？:？λ ratio ( ) are increased in sixteen patients with IgG4-related disease when compared to healthy controls. The increase of κ and λ free light chains probably reflects the marked polyclonal B cell activation of the disease. We could not assess in this small cohort of patients a significative correlation of serum free light chain levels and disease activity or extension. 1. Introduction Immunoglobulin free light chains (FLCs) are produced during antibody synthesis by B lymphocytes. Immunoglobulins have a tetrameric structure composed of two identical heavy and two identical light chains (kappa or lambda) linked together by disulphide bonds. Heavy and light chains assembly occurs in the endoplasmic reticulum. During antibody synthesis, there is an excess of light chain production. These FLCs are secreted into the circulation, where rapid renal clearance results in a short half-life of 2–6 hours [1]. Nowadays highly sensitive nephelometric immunoassay, with antibodies recognizing epitopes specific for free kappa (κ) or lambda (λ) light chains, are available [2]. Reference and diagnostic ranges for serum FLC (sFLC) and the κ？:？λ ratio have been determined with these assays [3]. In the context of a monoclonal gammopathy of undetermined significance the evaluation of the κ？:？λ ratio has been shown to correlate with the prognosis [4]. Moreover, this assay is now commonly used to quantify the monoclonal component in case of light chain multiple myeloma or AL amyloidosis [5, 6]. Decreased glomerular filtration rate (GFR) in renal insufficiency, associated either with a monoclonal gammopathy or other chronic kidney diseases, has an influence on FLC levels. Polyclonal sFLC levels are increased as a consequence of the reduction of their clearance [1]. The κ？:？λ ratio also increases because the κ FLC clearance is more influenced by the GFR than the λ FLC [1]. sFLC overproduction has also been reported in cases of a polyclonal increase of immunoglobulins. This has been shown in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sj？gren’s syndrome [7–9]. However, in a context of polyclonal hypergammaglobulinemia, the κ？:？λ ratio remains
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