Clone-directed therapy for proliferative glomerulonephritis with monoclonal immunoglobulin depositions: is it always necessary?
Rob C.M. van KruijsdijkAlferso C AbrahamsTri Q. NguyenMonique C. MinnemaJoannes F.M. JacobsMaarten Limper
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Abstract Monoclonal gammopathy of renal significance (MGRS) encompasses a group of disorders in which a monoclonal immunoglobulin (M-protein) secreted by a B-cell or plasma cell clone causes renal disease. Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a form of MGRS where M-protein is deposited in the glomerulus. Although evidence is limited, the current consensus is that therapy for PGNMID should be directed against the underlying clone. However, it is conceivable that there is heterogeneity in the renal prognosis of PGNMID and that not all patients have need for clone-directed therapy. Here, we report two cases of PGNMID with IgM-kappa gammopathy. In one case of a 53-year-old woman the glomerulonephritis resolved without clone-directed therapy. In the other case of a 34-year-old woman clone-directed therapy was discontinued due to adverse effects. Although no hematological response was achieved, the PGNMID resolved. In both cases there are no signs of a recurrent glomerulonephritis in over 3 years of follow-up. Here, we review the literature and suggest that some PGNMID patients have a favorable renal prognosis in whom clone-directed therapy can be withheld or postponed. Further research is warranted to yield predictors to identify these patients and to better understand the disease course of PGNMID.Keywords:
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Objective: Triclonal gammopathies, although considered a variant of monoclonal gammopathy of unknown signifi cance, have been shown to be associated with other malignancies and infl ammatory pathologies.There is sadly a paucity of triclonal gammopathies reported in the literature.Here, we present a case diagnosed with triclonal gammopathy/ MGUS to add to the small body of knowledge available about this rare condition.Methods: Review of the case history and laboratory investigations. Results:The case history and progression of disease of an 86 year old female diagnosed with triclonal gammopathy/ MGUS (by capillary electrophoresis and immunosubtraction), smoldering plasma cell myeloma, progressive paraproteinemia and worsening renal and hepatic functions and yet no detected bone marrow plasma cell clonality is described with relevant clinical investigations. Conclusion:Given the rarity of triclonal gammopathies, currently available research has yet to establish whether they arise from one clone or three unrelated clones of immunoglobulins.We discussed a case of triclonal gammopathy without any detected bone marrow plasma cell clonality.Increased awareness of this disorder and its associated analytical diffi culties can help in the formulation of future guidelines for their analysis and treatment, as more cases are catalogued.
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Direct measurement of monoclonal plasma cell mass in bone marrow biopsies may be a useful parameter to establish in plasma cell dyscrasia. In this study monoclonal plasma cells/mm in light chain immunoglobulin immunostained archival bone marrow sections from 22 patients in whom a diagnosis of multiple myeloma (MM) had been excluded but who had monoclonal proteins were counted by two observers at light microscopic level. There was good correlation between the counts of the two observers. The levels of monoclonal plasma cells/mm in biopsies were not related to the % counts in the aspirates taken at the same time as the biopsies. Three of seven patients with biopsy levels in excess of the polyclonal levels in patients without plasma cell dyscrasia developed progressive MM within the observation time. Monoclonal plasma cell levels/mm of bone marrow biopsies can be measured and they provide a useful parameter for the assessment of patients with low volume plasma cell dyscrasia.
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We present a patient with multiple myeloma and double (IgAk + IgGk) paraproteinaemia in the serum. Immunofluorescence analysis of bone marrow plasma cell with fluorochrome-conjugated goat antibodies specific for μ, δ, γ or α immunoglobulin heavy chain and k or λ light chains revealed the presence of a plasma cell clone synthesizing simultaneously γ, α and k chains. A minority of plasma cells synthesized γ or α chains separately. Moreover, in the patient's peripheral blood, a few cells with the morphology of lymphoplasmoblasts and simultaneously positive for γ, α and k chains were also detected. These results indicate that in this patient, the neoplastic plasma cell clone was 'frozen' at the differentiative step of the switch from IgG to IgA synthesis.
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Monoclonal immunoglobulins have been implicated in the development of C3 glomerulonephritis (C3GN) and Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID). We report a 58-year-old female who showed a switch from C3GN to PGNMID. She presented with mild proteinuria and normal renal function for the first time. Her renal biopsy showed a severe mesangial proliferation with isolated C3 deposits, thus being diagnosed as C3GN. Two years later, her condition became serious. Repeat renal biopsy showed a membranoproliferative glomerulonephritis with deposition of the κ light chain of IgG3 in the glomeruli. She was diagnosed with proliferative glomerulonephritis with monoclonal IgG deposits (IgG3-κ). This case demonstrates that there are several types of monoclonal gammopathy (MGP)-associated glomerulonephritis, and they can switch among each other in some patients.
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2 patients with multiple myeloma had the same type of crystals in plasma cells, B‐lympho‐cytes, and T‐lymphocytes. It is hypothesized that these crystals are formed in cells belonging to the same clone of pathological cells. The clone would then have to be derived from a common lymphocyte stem cell.
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Abstract Monoclonal gammopathy of renal significance (MGRS) encompasses a group of disorders in which a monoclonal immunoglobulin (M-protein) secreted by a B-cell or plasma cell clone causes renal disease. Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a form of MGRS where M-protein is deposited in the glomerulus. Although evidence is limited, the current consensus is that therapy for PGNMID should be directed against the underlying clone. However, it is conceivable that there is heterogeneity in the renal prognosis of PGNMID and that not all patients have need for clone-directed therapy. Here, we report two cases of PGNMID with IgM-kappa gammopathy. In one case of a 53-year-old woman the glomerulonephritis resolved without clone-directed therapy. In the other case of a 34-year-old woman clone-directed therapy was discontinued due to adverse effects. Although no hematological response was achieved, the PGNMID resolved. In both cases there are no signs of a recurrent glomerulonephritis in over 3 years of follow-up. Here, we review the literature and suggest that some PGNMID patients have a favorable renal prognosis in whom clone-directed therapy can be withheld or postponed. Further research is warranted to yield predictors to identify these patients and to better understand the disease course of PGNMID.
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