Monoclonal gammopathy of clinical significance (MGCS) is an umbrella term to describe a spectrum of disorders with remarkable organ dysfunctions from the underlying non-malignant secreting B cell clone. Although the clone is usually very small, it is associated with diverse clinical manifestations through different mechanisms, such as monoclonal protein deposition, biological activity of immunoglobulin, or cytokine hyper-secretion. Some predominantly involve a single organ, typically the nerve, kidney, or skin, and others are systemic diseases with syndromic presentations. Recognizing the clinical features with appropriate tissue biopsies is critical to making the diagnosis, especially when the kidneys or skin is affected. Treatment is often challenging and requires a multidisciplinary approach. In several conditions, immunomodulation with intravenous immunoglobulin and/or clone-directed therapy are the best options with significant improvement of clinical symptoms and reversal of organ dysfunctions.
Not every patient with a monoclonal gammopathy has MGCS, given the prevalence of true monoclonal gammopathy of undetermined significance in the elderly. Their various clinical manifestations and rarity can delay diagnosis, with devastating organ consequences. The underlying pathogenic mechanisms are complex and sometimes intertwined with several different components. Most treatment recommendations are based on anecdotal reports and retrospective experiences. Overall, more research efforts are required to better characterize these disorders from a multidisciplinary perspective, in order to pave the way to a pathogenesis-driven therapeutic approach. Therefore, the goal of this Research Topic is to compile articles on MGCS, aiming to (1) provide updated descriptions of their clinical profiles from an organ based approach, (2) delineate a novel pathophysiological basis underlying their different manifestations, (3) identify applicable clinical biomarkers to assist the diagnosis, risk stratification, and disease activity monitoring and, (4) guide the development of more targeted therapeutic options.
In this Research Topic, we welcome the submission of Original Research articles, Mini-Reviews, and Reviews that cover the novel pathogenesis, unique manifestations or profiles, clinically applicable biomarkers, and innovative therapeutic approaches of the following MGCS’s:
• Nerve predominant disorders: POEMS syndrome, distal acquired demyelinating symmetric neuropathy with monoclonal protein (DADS-M), chronic ataxic neuropathy, ophthalmoplegia, IgM paraprotein, cold agglutinins, and disialosyl antibodies (CANOMAD), or sporadic late-onset nemaline myopathy.
• Kidney predominant disorders: AL amyloidosis, monoclonal immunoglobulin deposition disease, proliferative glomerulonephritis with monoclonal immunoglobulin deposition (PGMID), light chain proximal tubulopathies, C3 glomerulonephritis, monoclonal gammopathy–associated thrombotic microangiopathy.
• Skin predominant disorders: Schnitzler syndrome, scleromyxedema, necrobiotica xanthogranuloma, acquired cutis laxa.
• Others: Clarkson syndrome, TEMPI syndrome, acquired C1 inhibitor deficiency, acquired von Willebrand disease, cold agglutinin disease.
Monoclonal gammopathy of clinical significance (MGCS) is an umbrella term to describe a spectrum of disorders with remarkable organ dysfunctions from the underlying non-malignant secreting B cell clone. Although the clone is usually very small, it is associated with diverse clinical manifestations through different mechanisms, such as monoclonal protein deposition, biological activity of immunoglobulin, or cytokine hyper-secretion. Some predominantly involve a single organ, typically the nerve, kidney, or skin, and others are systemic diseases with syndromic presentations. Recognizing the clinical features with appropriate tissue biopsies is critical to making the diagnosis, especially when the kidneys or skin is affected. Treatment is often challenging and requires a multidisciplinary approach. In several conditions, immunomodulation with intravenous immunoglobulin and/or clone-directed therapy are the best options with significant improvement of clinical symptoms and reversal of organ dysfunctions.
Not every patient with a monoclonal gammopathy has MGCS, given the prevalence of true monoclonal gammopathy of undetermined significance in the elderly. Their various clinical manifestations and rarity can delay diagnosis, with devastating organ consequences. The underlying pathogenic mechanisms are complex and sometimes intertwined with several different components. Most treatment recommendations are based on anecdotal reports and retrospective experiences. Overall, more research efforts are required to better characterize these disorders from a multidisciplinary perspective, in order to pave the way to a pathogenesis-driven therapeutic approach. Therefore, the goal of this Research Topic is to compile articles on MGCS, aiming to (1) provide updated descriptions of their clinical profiles from an organ based approach, (2) delineate a novel pathophysiological basis underlying their different manifestations, (3) identify applicable clinical biomarkers to assist the diagnosis, risk stratification, and disease activity monitoring and, (4) guide the development of more targeted therapeutic options.
In this Research Topic, we welcome the submission of Original Research articles, Mini-Reviews, and Reviews that cover the novel pathogenesis, unique manifestations or profiles, clinically applicable biomarkers, and innovative therapeutic approaches of the following MGCS’s:
• Nerve predominant disorders: POEMS syndrome, distal acquired demyelinating symmetric neuropathy with monoclonal protein (DADS-M), chronic ataxic neuropathy, ophthalmoplegia, IgM paraprotein, cold agglutinins, and disialosyl antibodies (CANOMAD), or sporadic late-onset nemaline myopathy.
• Kidney predominant disorders: AL amyloidosis, monoclonal immunoglobulin deposition disease, proliferative glomerulonephritis with monoclonal immunoglobulin deposition (PGMID), light chain proximal tubulopathies, C3 glomerulonephritis, monoclonal gammopathy–associated thrombotic microangiopathy.
• Skin predominant disorders: Schnitzler syndrome, scleromyxedema, necrobiotica xanthogranuloma, acquired cutis laxa.
• Others: Clarkson syndrome, TEMPI syndrome, acquired C1 inhibitor deficiency, acquired von Willebrand disease, cold agglutinin disease.
