[Nephropathy associated with monoclonal immunoglobulins: From clonal expansion B to renal toxicity of pathological immunoglobulins].

Germinal center regulation pathways are often involved in lymphomagenesis and myelomagenesis. Most of the lymphomas (and multiple myeloma) derive from post-germinal center B-cells that have undergone somatic hypermutation and class switch recombination. Hence, B-cell clonal expansion can be responsible for the presence of a monoclonal component (immunoglobulin) of variable titer which, owing to physicochemical properties, can provoke pathologically defined entities of diseases. These diseases can affect any functional part of the kidney, by multiple mechanisms, either well known or not. The presence of renal deposition is influenced by germinal gene involved, immunoglobulin primary structure, post-translational modifications and microenvironmental interactions. The two ways immunoglobulin can cause kidney toxicity are (i) an excess of production (overcoming catabolism power by proximal tubule epithelial cells) with an excess of free light chains within the distal tubules and a subsequent risk of precipitation due to local physicochemical properties; (ii) by structural characteristics that predispose immunoglobulin to a renal disease (whatever their titer). The purpose of this manuscript is to review literature concerning the pathophysiology of renal toxicities of clonal immunoglobulin, from molecular B-cell expansion mechanisms to immunoglobulin renal toxicity.