Two Cases of Proliferative Glomerulonephritis With Monoclonal IgG Deposits Treated With Renin Angiotensin Inhibition Alone With Long-term Follow-up.
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ABSTRACT:
SUBMITTER: Rosenstock JL
PROVIDER: S-EPMC8343764 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC8343787 | biostudies-literature
Project description:A 55-year-old man developed rapidly progressive glomerulonephritis and nephrotic syndrome. A kidney biopsy specimen showed diffuse proliferative and crescentic glomerulonephritis with monoclonal IgG1κ, humps, and nephritis-associated plasmin receptor, indicating infection-associated proliferative glomerulonephritis with monoclonal immunoglobulin G deposits (PGNMID). Despite dialysis-dependent renal failure, symptomatic therapy resulted in spontaneous recovery of the renal function, mimicking post-infectious glomerulonephritis (PIGN). A heterozygous complement factor H mutation was detected by comprehensive genetic testing of alternative pathway regulatory genes, which might lead to persistent infection-triggered alternative pathway activation and account for severe glomerulonephritis. Post-infectious PGNMID and PIGN might share common clinical presentations and pathogenesis related to the complement pathway.
| S-EPMC5457925 | biostudies-literature
Project description:BACKGROUND AND OBJECTIVES: Glomerular deposition of monoclonal Ig has been exceptionally described as the cause of membranoproliferative glomerulonephritis, through activation of the complement alternative pathway (CAP). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We retrospectively studied six adults with monoclonal gammopathy and glomerulonephritis (GN) characterized by isolated C3 deposits. RESULTS: All patients presented with hematuria, associated with chronic renal failure and proteinuria in five patients, three of whom had nephrotic syndrome. Five patients had monoclonal gammopathy of undetermined significance and one had smoldering myeloma. The serum monoclonal IgG (κ four of six, λ two of six) was associated with light chain (LC) proteinuria in five patients. Four patients had low serum C3 and/or factor B levels. C4, factor H (CFH), and I protein levels were normal in five of five patients; none had detectable C3NeF. IgG anti-CFH activity was positive in one case. No mutations in CFH, CFI, and MCP genes were identified in four of four patients. Deposits were intramembranous, subepithelial, and mesangial by electron microscopy, and stained positive for C3 (six of six), properdin, and CFH (two of two) but negative for Ig LC and heavy chains, C4, and C1q (6/6) by immunofluorescence. Five patients progressed to end-stage renal disease over a median period of 47 months, despite chemotherapy in four patients. In one patient, monoclonal λLC deposits were observed on a follow-up kidney biopsy after 4 years. CONCLUSIONS: GN with isolated glomerular C3 deposits might represent an unusual complication of plasma cell dyscrasia, related to complement activation through an autoantibody activity of the monoclonal Ig against a CAP regulator protein.
| S-EPMC3358988 | biostudies-other
Project description:Blockade of the renin-angiotensin system is renoprotective in a variety of chronic nephropathies, but the direct effect of such treatment in active, immune complex-mediated glomerulonephritis is unknown. This study investigated the short- and long-term effects of an angiotensin-converting enzyme inhibitor (enalapril) and an angiotensin II type 1 receptor blocker (losartan) in thymic stromal lymphopoietin transgenic (TSLPtg) mice, which develop mixed cryoglobulinemia and severe cryoglobulinemia-associated membranoproliferative glomerulonephritis. Enalapril and losartan each reduced hypertension, proteinuria, glomerular extracellular matrix deposition, and mesangial cell activation in TSLPtg mice. These renoprotective effects were not observed with hydralazine treatment, despite a similar antihypertensive effect. Treatment with enalapril or losartan also decreased renal plasminogen activator inhibitor-1 in TSLPtg mice, assessed by immunohistochemistry and quantitative real-time reverse transcriptase-PCR. None of the treatments affected immune complex deposition or macrophage infiltration. Overall, enalapril- and losartan-treated TSLPtg mice survived significantly longer than untreated TSLPtg mice. These studies demonstrate that angiotensin blockade may provide renoprotective benefits, independent of its BP-lowering effect, in the treatment of active immune complex-mediated glomerulonephritis.
| S-EPMC2396930 | biostudies-literature
Project description:A 74-year-old man presented with nephrotic syndrome and kidney insufficiency. Laboratory tests revealed monoclonal gammopathy of immunoglobulin A-lambda. Renal biopsy revealed diffuse mesangial proliferation and double-contoured basement membranes. Immunofluorescent analyses showed granular deposition of immunoglobulin A and C3 at the capillary walls and mesangial regions. Immunohistochemistry suggested monoclonal deposition of immunoglobulin A1-lambda. Electron microscopic analyses showed finely granular electron-dense deposits at mesangial and subendothelial areas. These findings suggested immunoglobulin A-type proliferative glomerulonephritis with monoclonal immunoglobulin deposits. Based on the results of bone marrow aspiration, multiple myeloma was diagnosed. Because the renal manifestation was considered to be affected by monoclonal gammopathy, chemotherapy was initiated rather than immunomodulatory therapy. Although bortezomib and dexamethasone proved ineffective, second chemotherapy with elotuzumab, lenalidomide, and dexamethasone was successful, and kidney function recovered. Effective treatments for proliferative glomerulonephritis with monoclonal immunoglobulin deposits have not been established. This represents the first description of a patient successfully treated for proliferative glomerulonephritis with monoclonal immunoglobulin deposits by chemotherapy using elotuzumab.
| S-EPMC7502091 | biostudies-literature
Project description:BackgroundGlomerulonephritis (GN) with non-Randall-type, non-cryoglobulinaemic monoclonal immunoglobulin G deposits encompasses rare diseases [proliferative GN with non-organized deposits (PGNMID) and immunotactoid GN] that cannot be distinguished without ultrastructural analysis by electron microscopy (EM).MethodsHere, we report and analyse the prognosis of 41 EM-proven (PGNMID for 39/41) and 22 non-EM-proven/DNAJB9-negative cases, diagnosed between 2001 and 2019 in 12 French nephrology centres.ResultsMedian (interquartile range) serum creatinine (SCr) at presentation was 150 (92-256) µmol/L. The predominant histological pattern was membranoproliferative GN (79%), with IgG3 (74%) kappa (78%) deposits the most frequently observed. Disease presentation and patient management were similar between EM-proven and non-EM-proven cases. A serum monoclonal spike was detected for 21 patients and 10 had an underlying haematological malignancy. First-line therapy was mixed between clone-targeted therapy (n = 33), corticosteroids (n = 9) and RAAS inhibitors (n = 19). After 6 months, nine patients achieved complete and 23 partial renal recovery. In univariate analysis, renal recovery was associated with baseline SCr (odds ratio 0.70, P = 0.07). After a median follow-up of 52 (35-74) months, 38% of patients had progressed to end-stage kidney disease independently associated with baseline SCr [hazard ratio (HR) 1.41, P = 0.003] and glomerular crescentic proliferation (HR 4.38, P = 0.004).ConclusionsOur results confirm that non-cryoglobulinaemic and non-Randall GN with monoclonal IgG deposits are rarely associated with haematological malignancy. The prognosis is uncertain but may be improved by early introduction of a specific therapy.
| S-EPMC9394706 | biostudies-literature
Project description: Not available
| S-EPMC8418982 | biostudies-literature
Project description:The diagnosis of membranoproliferative glomerulonephritis (MPGN) has recently undergone change from an electron microscopy-based classification scheme to one based largely on immunofluorescence findings. This change is due to the recognition that many of these cases are driven by abnormalities of the alternative complement cascade, resulting in the concept of C3 glomerulopathy. Here we reviewed our case files to identify those with an MPGN pattern that show false negative staining for monoclonal immunoglobulins by routine immunofluorescence. Monoclonal immunoglobulin deposits were unmasked by performing immunofluorescence on formalin-fixed paraffin embedded tissue after protease digestion. Clinico-pathological details of 16 such cases with a mean serum creatinine of 2.7 mg/dl and mean 24 h proteinuria of 7.1 g were then determined. Hypocomplementemia was present in two-thirds of patients. Fourteen patients had a paraprotein on serum immunofixation, all of which matched the biopsy immunofluorescence staining pattern. Bone marrow biopsy showed plasma cell dyscrasia or B-cell lymphoproliferative disorder in 13 patients. Ten of these patients had findings on biopsy most consistent with C3 glomerulonephritis prior to performing paraffin immunofluorescence. Thus a high index of suspicion is necessary to avoid misdiagnosis in these cases, as many would have been mistakenly diagnosed as C3 glomerulopathy or unclassified MPGN if paraffin immunofluorescence was not performed.
| S-EPMC4687465 | biostudies-literature
Project description:Structural aberrations of O-linked glycans present in the IgA1 hinge region are associated with IgA nephropathy, but their contribution to its pathogenesis remains incompletely understood. In this study, mice implanted with hybridoma secreting 6-19 IgA anti-IgG2a rheumatoid factor, but not 46-42 IgA rheumatoid factor bearing the same IgA allotype, developed mesangial deposits consisting of IgA, IgG2a, and C3. Studies in immunoglobulin- and C3-deficient mice revealed that the development of these glomerular lesions required the formation of IgA-IgG2a immune complexes and subsequent activation of complement. The proportion of polymeric and monomeric forms, the IgG2a-binding affinity, and the serum levels of IgA-IgG2a immune complexes were similar between 6-19 IgA- and 46-42 IgA-injected mice. In contrast, the analysis of oligosaccharide structures revealed highly galactosylated O-linked glycans in the hinge region of 6-19 IgA and poorly O-glycosylated in the hinge region of 46-42 IgA. Furthermore, the structure of N-linked glycans in the CH1 domain was the complex type in 6-19 IgA and the hybrid type in 46-42 IgA. In summary, this study demonstrates the presence of O-linked glycans in the hinge region of mouse IgA and suggests that 6-19 IgA rheumatoid factor-induced GN could serve as an experimental model for IgA nephropathy.
| S-EPMC3294307 | biostudies-literature