Revisiting proliferative glomerulonephritis with monoclonal immunoglobulin deposits through immunoglobulin repertoire sequencing
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PROVIDER: PRJEB88838 | ENA |
REPOSITORIES: ENA
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Project description:As aging increases, monoclonal gammopathy is becoming more common and monoclonal gammopathy of renal significance (MGRS) is gaining attention due to frequent renal involvement. Within MGRS, proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a special category. The disease was first described in 2004 and the research history on it is relatively short. Compared with other MGRS, the detection rate of circulating clones is lower in patients with PGNMID, which is easy to miss and misdiagnose in clinical work. In this review, the etiology and clinical features of PGNMID are discussed. It is noted that PGNMID is associated not only with MGRS, but also with malignancy, infection and other factors. PGNMID is not a disease exclusive to the elderly-young people can also develop this disease. Due to the low detection rate of circulating clones in most patients, confirmation of the disease needs to be combined with renal pathology, which emphasizes the importance of completing light and heavy chain subtype staining. Treatment options for patients with PGNMID differ by etiology. For MGRS-associated PGNMID, the current treatment is primarily empirical and more research evidence is needed to fill the treatment gap.
| S-EPMC9155251 | biostudies-literature
Project description: Not available
| S-EPMC8343787 | biostudies-literature
Project description:Introduction Immunomodulatory drugs (IMiDs) plus dexamethasone are effective for plasma cell dyscrasias, but the treatment efficacy of IMiD in proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) has been rarely reported. Methods We retrospectively analyzed the clinicopathologic data of 64 patients with PGNMID (steroid, IMiD, and bortezomib and dexamethasone/Rituximab [BD/RTX] groups) from January 1, 2010 to December 31, 2020, at the National Clinical Research Center of Kidney Disease in Nanjing. The prognosis of patients receiving different treatment regimens were compared. Factors potentially affecting renal prognosis and renal response were evaluated. Results Twenty-eight, 26 and 10 PGNMID patients were divided into IMiD group, steroid group and BD/RTX group respectively. The rate of serum M protein detection was significantly lower in the steroid group than in the other 2 groups. Renal remission (P = 0.001 and P = 0.03, respectively) rates and renal complete remission (CR) (P = 0.001 and P = 0.01, respectively) rates were significantly higher in the IMiD and BD/RTX groups than in the steroid group at the last follow-up. Multivariate logistic analysis identified that hypertension and high serum creatinine (SCr) levels (>1.24 mg/dl) decreased renal remission, whereas low C3 levels, IMiD and BD/RTX treatments were positively associated with renal remission. Multivariate Cox analysis identified IgG3 in renal tissue and high SCr levels as poor renal prognostic indicators. Severe adverse events were more common in the IMiD and BD/RTX groups than in the steroid group (P = 0.072 and P = 0.035, respectively). Conclusion Our results suggest that IMiDs plus dexamethasone is effective for achieving renal remission in PGNMID patients. Graphical abstract
| S-EPMC9546741 | 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:Despite treatment with immunosuppressive or clone-targeted chemotherapy, patients with proliferative glomerulonephritis with monoclonal immunoglobulin deposit (PGNMID) frequently progress into end-stage kidney failure, and early recurrence of PGNMID after kidney transplantation is common. The standard management of PGNMID has been unclear, currently based on data from small cohorts, which requires a need for additional therapeutic regimens in this disease. A human IgG monoclonal antibody that targets CD38 (daratumumab) was recently identified as a potential therapeutic option for treating PGNMID. To date, rare data on the application of daratumumab in patients with PGNMID after kidney transplantation have been reported. Herein, we first described a unique patient with recurrent PGNMID in kidney allograft who was treated with daratumumab after not responding to bortezomib-based regimens. Daratumumab was shown to successfully reduce proteinuria with stabilizing kidney function and was well-tolerated in this patient, which supports that daratumumab appears to be a viable option for treatment-resistant PGNMID.
| S-EPMC11786820 | biostudies-literature
Project description: Not available
| S-EPMC7270977 | 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: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:BackgroundTreatment of proliferative GN with monoclonal Ig deposits (PGNMID) is not established. A monoclonal anti-CD38 antibody (daratumumab) is effective in treating multiple myeloma. Abnormal plasma cell clones may play a role in the pathogenesis of PGNMID.MethodsWe evaluated daratumumab's safety and efficacy in an open-label, phase 2 trial in 11 adults with PGNMID and one with C3 glomerulopathy (C3G) with monoclonal gammopathy. Patients had an eGFR >20 ml/min per 1.73 m2 and proteinuria >1 g/d. They received daratumumab intravenously (16 mg/kg) once weekly for 8 weeks, and then every other week for eight additional doses. Primary outcome was safety, defined as major infections, grade 3 or 4 anemia, leukopenia, or thrombocytopenia. Secondary outcomes were rate of complete remission (proteinuria <500 mg/d with <15% decline in baseline eGFR) or partial remission (>50% reduction in 24-hour proteinuria with <30% decline in eGFR) and proteinuria at 6 and 12 months.ResultsOne patient with C3G had GN unrelated to the monoclonal gammopathy, and one with PGNMID did not complete the first infusion. Five serious adverse events occurred. During the 12 months of the trial, six of the ten patients with PGNMID who received at least one dose of daratumumab had a partial response, and four had a complete response (an overall response rate of 100%). Three patients experienced relapse, two of whom re-entered partial remission after resuming daratumumab therapy. Proteinuria declined significantly, from a median of 4346 mg/d to 1264 mg/d by 12 months.ConclusionsDaratumumab demonstrated an acceptable safety profile and resulted in significant improvement in proteinuria while stabilizing kidney function in patients with PGNMID, suggesting the drug merits further investigation.Clinical trial registry name and registration numberDaratumumab in Treatment of PGNMID and C3 GN, NCT03095118.
| S-EPMC8259683 | biostudies-literature