Monoclonal immunoglobulin-related nephropathies: From B cell clonal expansion to the renal toxicity of pathological immunoglobulins
Gueye, Serigne
Monoclonal immunoglobulin-related nephropathies: From B cell clonal expansion to the renal toxicity of pathological immunoglobulins - 2022.
77
Germinal center regulation pathways are often involved in lymphomagenesis and myelomagenesis. Most lymphomas (and multiple myeloma) derive from post-germinal center B cells that have undergone somatic hypermutation and class switch recombination. B cell clonal expansion is thus sometimes responsible for the presence of a monoclonal component (immunoglobulin) of variable titer that, owing to physicochemical properties, can provoke pathologically defined disease entities. These diseases can affect any functional part of the kidney, by multiple mechanisms, some well known and others not. The presence of renal deposits is influenced by the germinal gene involved, the primary structure of the immunoglobulin, post-translational modifications, and microenvironmental interactions. Pathological immunoglobulins can cause renal toxicity in two ways: (i) excess production (overcoming the catabolism capacity of 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 the immunoglobulin to causing renal disease (whatever their titer). The purpose of this article is to review the literature concerning the pathophysiology of renal toxicities of clonal immunoglobulin, from molecular B cell expansion mechanisms to immunoglobulin renal toxicity.
Monoclonal immunoglobulin-related nephropathies: From B cell clonal expansion to the renal toxicity of pathological immunoglobulins - 2022.
77
Germinal center regulation pathways are often involved in lymphomagenesis and myelomagenesis. Most lymphomas (and multiple myeloma) derive from post-germinal center B cells that have undergone somatic hypermutation and class switch recombination. B cell clonal expansion is thus sometimes responsible for the presence of a monoclonal component (immunoglobulin) of variable titer that, owing to physicochemical properties, can provoke pathologically defined disease entities. These diseases can affect any functional part of the kidney, by multiple mechanisms, some well known and others not. The presence of renal deposits is influenced by the germinal gene involved, the primary structure of the immunoglobulin, post-translational modifications, and microenvironmental interactions. Pathological immunoglobulins can cause renal toxicity in two ways: (i) excess production (overcoming the catabolism capacity of 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 the immunoglobulin to causing renal disease (whatever their titer). The purpose of this article is to review the literature concerning the pathophysiology of renal toxicities of clonal immunoglobulin, from molecular B cell expansion mechanisms to immunoglobulin renal toxicity.
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