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Barbour SJ, Coppo R, Er L, et al., 2024, Histologic and Clinical Factors Associated with Kidney Outcomes in IgA Vasculitis Nephritis., Clin J Am Soc Nephrol, Vol: 19, Pages: 438-451
BACKGROUND: Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts. METHODS: Biopsies from 262 children and 99 adults with IgA vasculitis nephritis ( N =361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists. MEST-C scores were assessed for correlation with eGFR/proteinuria at biopsy. Because most patients ( N =309, 86%) received immunosuppression, risk factors for outcomes were evaluated in this group using latent class mixed models to identify classes of eGFR trajectories over a median follow-up of 2.7 years (interquartile range, 1.2-5.1). Clinical and histologic parameters associated with each class were determined using logistic regression. RESULTS: M, E, T, and C scores were correlated with either eGFR or proteinuria at biopsy. Two classes were identified by latent class mixed model, one with initial improvement in eGFR followed by a late decline (class 1, N =91) and another with stable eGFR (class 2, N =218). Class 1 was associated with a higher risk of an established kidney outcome (time to ≥30% decline in eGFR or kidney failure; hazard ratio, 5.84; 95% confidence interval, 2.37 to 14.4). Among MEST-C scores, only E1 was associated with class 1 by multivariable analysis. Other factors associated with class 1 were age 18 years and younger, male sex, lower eGFR at biopsy, and extrarenal noncutaneous disease. Fibrous crescents without active changes were associated with class 2. CONCLUSIONS: Kidney outcome in patients with biopsied IgA vasculitis nephritis treated with immunosuppression was determined by clinical risk factors and endocapillary hypercellularity (E1) and fibrous crescents, which are features that are not part of the International Study of Diseases of Children classifica
Tam FWK, Tumlin J, Barratt J, et al., 2023, Randomized trial on the effect of an oral spleen tyrosine kinase inhibitor in the treatment of IgA nephropathy, Kidney International Reports, Vol: 8, Pages: 2546-2556, ISSN: 2468-0249
IntroductionWe reported increased spleen tyrosine kinase (SYK) expression in kidney biopsies of patients with IgA nephropathy (IgAN) and that inhibition of SYK reduces inflammatory cytokines production from IgA stimulated mesangial cells.MethodsThis study was a double-blind, randomized, placebo-controlled phase 2 trial of fostamatinib (an oral SYK inhibitor) in 76 patients with IgAN. Patients were randomized to receive placebo, fostamatinib at 100 mg or 150 mg twice daily for 24 weeks on top of maximum tolerated dose of renin-angiotensin system inhibitors. The primary end point was reduction of proteinuria. Secondary end points included change from baseline in estimated glomerular filtration rate (eGFR) and kidney histology.ResultsAlthough we could not detect significant reduction in proteinuria with fostamatinib overall, in a predetermined subgroup analysis, there was a trend for dose-dependent reduction in median proteinuria (from baseline to 24 weeks by 14%, 27%, and 36% in the placebo, fostamatinib 100 mg, and 150 mg groups, respectively) in patients with baseline urinary protein-to-creatinine ratios (UPCR) more than 1000 mg/g. Kidney function (eGFR) remained stable in all groups. Fostamatinib was well-tolerated. Side effects included diarrhea, hypertension, and increased liver enzymes. Thirty-nine patients underwent repeat biopsy showing reductions in SYK staining associated with therapy at low dose (−1.5 vs. 1.7 SYK+ cells/glomerulus in the placebo group, P < 0.05).ConclusionsThere was a trend toward reduction in proteinuria with fostamatinib in a predefined analysis of high risk patients with IgAN despite maximal care, as defined by baseline UPCR greater than 1000 mg/g. Further study may be warranted.
Nester C, Appel GB, Bomback AS, et al., 2023, Clinical Outcomes of Patients with C3G or IC-MPGN Treated with the Factor D Inhibitor Danicopan: Final Results from Two Phase 2 Studies (vol 53, pg 687, 2023), AMERICAN JOURNAL OF NEPHROLOGY, ISSN: 0250-8095
Podos SD, Trachtman H, Appel GB, et al., 2023, Baseline Clinical Characteristics and Complement Biomarkers of Patients with C3 Glomerulopathy Enrolled in Two Phase 2 Studies Investigating the Factor D Inhibitor Danicopan, AMERICAN JOURNAL OF NEPHROLOGY, Vol: 53, Pages: 675-686, ISSN: 0250-8095
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Nester C, Appel GB, Bomback AS, et al., 2023, Clinical Outcomes of Patients with C3G or IC-MPGN Treated with the Factor D Inhibitor Danicopan: Final Results from Two Phase 2 Studies, AMERICAN JOURNAL OF NEPHROLOGY, Vol: 53, Pages: 687-700, ISSN: 0250-8095
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- Citations: 9
Bolognesi MM, Capitoli G, Galimberti S, et al., 2022, Dissecting the histological features of lupus nephritis highlights new common patterns of injury in class III/IV, ANNALS OF THE RHEUMATIC DISEASES, Vol: 81, Pages: 1704-1711, ISSN: 0003-4967
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- Citations: 5
Vivarelli M, Dixon BP, Fakhouri F, et al., 2022, PHASE 3, RANDOMIZED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF PEGCETACOPLAN IN TREATMENT OF C3G OR IC-MPGN, Publisher: SPRINGER, Pages: 2946-2947, ISSN: 0931-041X
Pickering M, Dixon B, Walker P, et al., 2022, Corrigendum to PHASE 2 STUDY TO EVALUATE EFFICACY AND SAFETY OF PEGCETACOPLAN IN THE TREATMENT OF PATIENTS WITH POSTTRANSPLANT RECURRENCE OF C3G OR IC MPGN(VOL 7 , PAGE 2321, YEAR 2022), KIDNEY INTERNATIONAL REPORTS, Vol: 7, Pages: 2321-2321, ISSN: 2468-0249
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- Citations: 1
Tang X, VanBeek C, Haas M, et al., 2022, Cell-Mediated Glomerulonephritis Without Immune Complexes in Native Kidney Biopsies: A Report of 7 Cases br, AMERICAN JOURNAL OF KIDNEY DISEASES, Vol: 80, Pages: 416-421, ISSN: 0272-6386
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Roufosse C, Cook H, Dominy K, et al., 2022, Diagnostic application of transcripts associated with antibody-mediated rejection in kidney transplant biopsies, Nephrology Dialysis Transplantation, Vol: 37, Pages: 1576-1584, ISSN: 0931-0509
BackgroundThe diagnosis of antibody-mediated rejection (AMR) is reached using the Banff Classification for Allograft Pathology, which now includes gene expression analysis. In this study, we investigate the application of “Increased Expression Of Thoroughly Validated Gene Transcripts/Classifiers Strongly Associated With AMR” as a diagnostic criteria.MethodWe used qRT-PCR for 10 genes associated with AMR in a retrospective cohort of 297 transplant biopsies, including biopsies that met the full diagnostic criteria for AMR, even without molecular data (AMR, n = 27); biopsies that showed features of AMR, but that would only meet criteria for AMR with increased transcripts (AMRsusp, n = 49) and biopsies that would never meet criteria for AMR (No-AMR, n = 221).ResultsA 10-gene AMR score trained by a receiver-operating characteristic to identify AMR found 16 cases with a high score amongst the AMRsusp cases (AMRsusp-high) that had significantly worse graft survival than those with a low score (AMRsusp-low) (n = 33). In both univariate and multivariate Cox regression analysis, the AMR 10-gene score was significantly associated with an increased hazard ratio for graft loss in the AMRsusp group (HR 1.109, p = 0.004 and HR 1.138, p = 0.012), but not in the whole cohort. Net reclassification index and integrated discrimination improvement analyses demonstrated improved risk classification and superior discrimination respectively for graft loss when considering the gene score in addition to histological and serological data, but only in the AMRsusp group, not the whole cohort.ConclusionsThis study provides evidence that a gene score strongly associated with AMR helps identify cases at higher risk of graft loss in biopsies that are suspicious for AMR but don’t meet full criteria.
Lomax-Browne HJ, Medjeral-Thomas NR, Barbour SJ, et al., 2022, Association of histologic parameters with outcome in C3 glomerulopathy and idiopathic immunoglobulin-associated membranoproliferative glomerulonephritis, Clinical Journal of the American Society of Nephrology, Vol: 17, Pages: 994-1007, ISSN: 1555-9041
Background and objectivesC3 glomerulopathy and idiopathic immunoglobulin-associated membranoproliferative glomerulonephritis (Ig-MPGN) are kidney diseases characterised by abnormal glomerular complement C3 deposition. These conditions are heterogeneous in outcome, but approximately 50% of patients reach end stage kidney disease within 10 years. Design, setting, participants and measurementsTo improve identification of patients with poor prognosis we performed a detailed analysis of percutaneous kidney biopsies in a large cohort of patients. Using a validated histological scoring system, we analysed 156 native diagnostic kidney biopsies from a retrospective cohort of 123 patients with C3 glomerulopathy and 33 patients with Ig-MPGN. We used linear regression, survival analysis and Cox proportional hazards models to assess the relationship between histological and clinical parameters with outcome. ResultsFrequent biopsy features were mesangial expansion and hypercellularity, glomerular basement membrane (GBM) double contours and endocapillary hypercellularity. Multivariable analysis showed negative associations between estimated glomerular filtration rate (eGFR) and crescents, interstitial inflammation, and interstitial fibrosis and tubular atrophy (IFTA). Proteinuria positively associated with endocapillary hypercellularity and GBM double contours. Analysis of second native biopsies did not demonstrate associations between immunosuppression treatment and improvement in histology. Using a composite outcome, risk of progression to kidney failure associated with eGFR and proteinuria at time of biopsy, and cellular/fibrocellular crescents, segmental sclerosis and IFTA scores. ConclusionsOur detailed assessment of kidney biopsy data indicated that cellular/fibrocellular crescents and IFTA scores were significant determinants of deterioration in kidney function.
Barbour SJ, Coppo R, Zhang H, et al., 2022, Application of the International IgA Nephropathy Prediction Tool one or two years post-biopsy., Kidney Int, Vol: 102, Pages: 160-172
The International IgA Nephropathy (IgAN) Prediction Tool is the preferred method in the 2021 KDIGO guidelines to predict, at the time of kidney biopsy, the risk of a 50% drop in estimated glomerular filtration rate or kidney failure. However, it is not known if the Prediction Tool can be accurately applied after a period of observation post-biopsy. Using an international multi-ethnic derivation cohort of 2,507 adults with IgAN, we updated the Prediction Tool for use one year after biopsy, and externally validated this in a cohort of 722 adults. The original Prediction Tool applied at one-year without modification had a coefficient of variation (R2) of 55% and 54% and four-year concordance (C statistic) of 0.82 but poor calibration with under-prediction of risk (integrated calibration index (ICI) 1.54 and 2.11, with and without race, respectively). Our updated Prediction Tool had a better model fit with higher R2 (61% and 60%), significant increase in four-year C-statistic (0.87 and 0.86) and better four-year calibration with lower ICI (0.75 and 0.35). On external validation, the updated Prediction Tool had similar R2 (60% and 58%) and four-year C-statistics (both 0.85) compared to the derivation analysis, with excellent four-year calibration (ICI 0.62 and 0.56). This updated Prediction Tool had similar prediction performance when used two years after biopsy. Thus, the original Prediction Tool should be used only at the time of biopsy whereas our updated Prediction Tool can be used for risk stratification one or two years post-biopsy.
Bos EMJ, Sangle SR, Wilhelmus S, et al., 2022, Use of Glomerular CD68+ Cells as a Surrogate Marker for Endocapillary Hypercellularity in Lupus Nephritis, KIDNEY INTERNATIONAL REPORTS, Vol: 7, Pages: 841-847, ISSN: 2468-0249
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Prendecki M, McAdoo SP, Turner-Stokes T, et al., 2022, Glomerulonephritis and autoimmune vasculitis are independent of P2RX7 but may depend on alternative inflammasome pathways., Journal of Pathology, Vol: 257, ISSN: 0022-3417
P2RX7, an ionotropic receptor for extracellular ATP, is expressed on immune cells, including macrophages, monocytes and dendritic cells and is up-regulated on non-immune cells following injury. P2RX7 plays a role in many biological processes, including production of pro-inflammatory cytokines such as IL-1β via the canonical inflammasome pathway. P2RX7 has been shown to be important in inflammation and fibrosis and may also play a role in autoimmunity. We have developed and phenotyped a novel P2RX7 knock-out (KO) inbred rat strain and taking advantage of the human-resembling unique histopathological features of rat models of glomerulonephritis, we induced three models of disease: nephrotoxic nephritis, experimental autoimmune glomerulonephritis, and experimental autoimmune vasculitis. We found that deletion of P2RX7 does not protect rats from models of experimental glomerulonephritis or the development of autoimmunity. Notably, treatment with A-438079, a P2RX7 antagonist, was equally protective in WKY WT and P2RX7 KO rats, revealing its 'off-target' properties. We identify a novel ATP/P2RX7/K+ efflux-independent and caspase-1/8-dependent pathway for production of IL-1β in rat dendritic cells, which was absent in macrophages. Taken together, these results comprehensively establish that inflammation and autoimmunity in glomerulonephritis is independent of P2RX7 and reveals the off-target properties of drugs previously known as selective P2RX7 antagonists. Rat mononuclear phagocytes may be able to utilise an 'alternative inflammasome' pathway to produce IL-1β independently of P2RX7, which may account for the susceptibility of P2RX7 KO rats to inflammation and autoimmunity in glomerulonephritis. This article is protected by copyright. All rights reserved.
Tempest-Roe S, Prendecki M, McAdoo S, et al., 2022, Inhibition of spleen tyrosine kinase decreases donor specific antibody levels in a rat model of sensitization, Scientific Reports, Vol: 12, ISSN: 2045-2322
Antibody mediated rejection is a major cause of renal allograft loss. Circulating preformed donor specific antibodies (DSA) can result as a consequence of blood transfusion, pregnancy or prior transplantation. Current treatment strategies are limited due to partial or transient efficacy, adverse side-effects or patient unsuitability. Previous in vivo studies exploring autoimmune diseases have shown that spleen tyrosine kinase (SYK) signalling is involved in the development of pathogenic autoantibody. The role of SYK in allogenic antibody production is unknown, and we investigated this in a rodent model of sensitization, established by the transfusion of F344 whole blood into LEW rats. Two-week treatment of sensitized rats with selective SYK inhibitor fostamatinib strongly blocked circulating DSA production without affecting overall total immunoglobulin levels, and inhibition was sustained up to 5 weeks post-completion of the treatment regimen. Fostamatinib treatment did not affect mature B cell subset or plasma cell levels, which remained similar between non-treated controls, vehicle treated and fostamatinib treated animals. Our data indicate fostamatinib may provide an alternative therapeutic option for patients who are at risk of sensitization following blood transfusion while awaiting renal transplant.
Gilmore A, Wilson H, Cairns T, et al., 2022, Immune gene expression and functional networks in distinct lupus nephritis classes, Lupus Science & Medicine, Vol: 9, ISSN: 2053-8790
Objective: To explore the utility of the NanoString platform in elucidating kidney immune transcripts for class III, IV and V lupus nephritis (LN) using a retrospective cohort of formalin-fixed paraffin-embedded (FFPE) kidney biopsy tissue.Methods: Immune gene transcript analysis was performed using the NanoString nCounter platform on RNA from LN (n=55), thin basement membrane disease (TBM, n=14) and membranous nephropathy (MN, n=9) FFPE kidney biopsy tissue. LN samples consisted of single class III (n=11), IV (n=23) and V (n=21) biopsies with no mixed lesions. Differential gene expression was performed with NanoString nSolver, with visualisations of volcano plots and heatmaps generated in R. Significant transcripts were interrogated to identify functional networks using STRING and Gene ontogeny terms. Results: In comparison to TBM, we identified 52 significantly differentially expressed genes common to all three LN classes. Pathway analysis showed enrichment for type I interferon (IFN) signalling, complement and MHC II pathways, with most showing the highest expression in class IV LN. Our class IV LN biopsies also showed significant upregulation of NF-κB signalling and immunological enrichment in comparison to class V LN biopsies. Transcripts from the type I IFN pathway distinguished class V LN from MN. Conclusion: Our whole kidney section transcriptomic analysis provided insights into the molecular profile of class III, IV and V LN. The data highlighted important pathways common to all three classes and pathways enriched in our class IV LN biopsies. The ability to reveal molecular pathways in LN using FFPE whole biopsy sections could have clinical utility in treatment selection for LN.
Rovin BH, Adler SG, Barratt J, et al., 2022, Executive summary of the KDIGO 2021 guideline for the management of glomerular diseases, Nephrology and Dialysis, Vol: 24, Pages: 21-51, ISSN: 1680-4422
The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Glomerular Diseases is an update to the KDIGO 2012 guideline. The aim is to assist clinicians caring for individuals with glomerulonephritis (GN), both adults and children. The scope includes various glomerular diseases, including IgA nephropathy and IgA vasculitis, membranous nephropathy, nephrotic syndrome, minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), infectionrelated GN, antineutrophil cytoplasmic antibody (ANCA) vasculitis, lupus nephritis, and anti-glomerular basement membrane antibody GN. In addition, this guideline will be the fi rst to address the subtype of complement-mediated diseases. Each chapter follows the same format providing guidance related to diagnosis, prognosis, treatment, and special situations. The goal of the guideline is to generate a useful resource for clinicians and patients by providing actionable recommendations based on evidence syntheses, with useful infographics incorporating views from experts in the fi eld. Another aim is to propose research recommendations for areas where there are gaps in knowledge. The guideline targets a broad global audience of clinicians treating GN while being mindful of implications for policy and cost. Development of this guideline update followed an explicit process whereby treatment approaches and guideline recommendations are based on systematic reviews of relevant studies, and appraisal of the quality of the evidence and the strength of recommendations followed the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. Limitations of the evidence are discussed, with areas of future research also presented.
Podos S, Nester C, Appel G, et al., 2022, Clinical and biomarker characteristics of patients with C3G enrolled in two phase II studies investigating the factor D inhibitor danicopan, Publisher: PERGAMON-ELSEVIER SCIENCE LTD, Pages: 148-148, ISSN: 0161-5890
Fakhouri F, Dixon B, Pickering M, et al., 2021, Phase 3, randomized, multicenter study to evaluate the efficacy and safety of pegcetacoplan in treatment of C3G or IC-MPGN, Publisher: E M H SWISS MEDICAL PUBLISHERS LTD, Pages: 33S-33S, ISSN: 1424-7860
Fakhouri F, Walker P, Dixon B, et al., 2021, A phase 2 study to evaluate the efficacy and safety of pegcetacoplan in the treatment of patients with posttransplant recurrence of C3G or IC-MPGN, Publisher: E M H SWISS MEDICAL PUBLISHERS LTD, Pages: 28S-28S, ISSN: 1424-7860
Wong EKS, Marchbank KJ, Lomax-Browne H, et al., 2021, C3 Glomerulopathy and Related Disorders in Children: Etiology-Phenotype Correlation and Outcomes, CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, Vol: 16, Pages: 1639-1651, ISSN: 1555-9041
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Prendecki M, Gulati K, Turner-Stokes T, et al., 2021, Characterisation of an enhanced preclinical model of experimental MPO-ANCA autoimmune vasculitis, Journal of Pathology, Vol: 255, Pages: 107-119, ISSN: 0022-3417
Experimental autoimmune vasculitis (EAV) is a model of antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) induced by immunisation of susceptible rat strains with myeloperoxidase (MPO). Animals develop circulating MPO-ANCA, pulmonary haemorrhage and glomerulonephritis, although renal injury is mild and recovers spontaneously without treatment. In this study we aimed to augment the severity of glomerulonephritis. Following induction of EAV on day 0, a sub-nephritogenic dose of nephrotoxic serum (NTS) containing heterologous antibodies to glomerular basement membrane was administered on day 14. This resulted in a significant increase in disease severity at day 28 compared to MPO immunisation alone - with more urinary abnormalities, infiltrating glomerular leucocytes, and crescent formation that progressed to glomerular and tubulointerstitial scarring by day 56, recapitulating important features of human disease. Importantly, the glomerulonephritis remained pauci-immune, and was strictly dependent on the presence of autoimmunity to MPO, as there was no evidence of renal disease following administration of sub-nephritogenic NTS alone or after immunisation with a control protein in place of MPO. Detailed phenotyping of glomerular leucocytes identified an early infiltrate of non-classical monocytes following NTS administration that, in the presence of autoimmunity to MPO, may initiate the subsequent influx of classical monocytes which augment glomerular injury. We also showed that this model can be used to test novel therapeutics by using a small molecule kinase inhibitor (fostamatinib) that rapidly attenuated both glomerular and pulmonary injury over a four-day treatment period. We believe that this enhanced model of MPO-AAV will prove useful for the study of glomerular leucocyte behaviour and novel therapeutics in AAV in the future. This article is protected by copyright. All rights reserved.
Rovin BH, Adler SG, Barratt J, et al., 2021, Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases, KIDNEY INTERNATIONAL, Vol: 100, Pages: 753-779, ISSN: 0085-2538
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- Citations: 201
Dixon BP, Fakhouri F, Pickering MC, et al., 2021, PHASE 3, RANDOMIZED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF PEGCETACOPLAN IN TREATMENT OF C3G OR IC-MPGN, Publisher: SPRINGER, Pages: 3399-3400, ISSN: 0931-041X
Kidney Disease Improving Global Outcomes KDIGO Glomerular Diseases Work Group, 2021, KDIGO 2021 clinical practice Guideline for the management of glomerular diseases., Kidney International, Vol: 100, Pages: S1-S276, ISSN: 0085-2538
This guideline is published as a supplement supported by KDIGO. The development and publication of this guideline are strictly funded by KDIGO, and neither KDIGO nor its guideline Work Group members sought or received monies or fees from corporate or commercial entities in connection with this work. The opinions or views expressed in this professional education supplement are those of the authors and do not necessarily reflect the opinions or recommendations of the International Society of Nephrology or Elsevier. Dosages, indications, and methods of use for products that are referred to in the supplement by the authors may reflect their clinical experience or may be derived from the professional literature or other clinical sources. Because of the differences between in vitro and in vivo systems and between laboratory animal models and clinical data in humans, in vitro and animal data may not necessarily correlate with clinical results.
Dotz V, Visconti A, Lomax-Browne HJ, et al., 2021, O- and N-glycosylation of serum immunoglobulin A is associated with IgA nephropathy and glomerular function., Journal of the American Society of Nephrology, Vol: 32, Pages: 1-12, ISSN: 1046-6673
BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide and is a leading cause of renal failure. The disease mechanisms are not completely understood, but a higher abundance of galactose-deficient IgA is recognized to play a crucial role in IgAN pathogenesis. Although both types of human IgA (IgA1 and IgA2) have several N-glycans as post-translational modification, only IgA1 features extensive hinge-region O-glycosylation. IgA1 galactose deficiency on the O-glycans is commonly detected by a lectin-based method. To date, limited detail is known about IgA O- and N-glycosylation in IgAN. METHODS: To gain insights into the complex O- and N-glycosylation of serum IgA1 and IgA2 in IgAN, we used liquid chromatography-mass spectrometry (LC-MS) for the analysis of tryptic glycopeptides of serum IgA from 83 patients with IgAN and 244 age- and sex-matched healthy controls. RESULTS: Multiple structural features of N-glycosylation of IgA1 and IgA2 were associated with IgAN and glomerular function in our cross-sectional study. These features included differences in galactosylation, sialylation, bisection, fucosylation, and N-glycan complexity. Moreover, IgA1 O-glycan sialylation was associated with both the disease and glomerular function. Finally, glycopeptides were a better predictor of IgAN and glomerular function than galactose-deficient IgA1 levels measured by lectin-based ELISA. CONCLUSIONS: Our high-resolution data suggest that IgA O- and N-glycopeptides are promising targets for future investigations on the pathophysiology of IgAN and as potential noninvasive biomarkers for disease prediction and deteriorating kidney function.
Singh S, Roufosse C, Smith A, et al., 2021, An Audit of Electron Microscopic Evaluation of Native Renal Biopsies, Publisher: WILEY, Pages: S47-S47, ISSN: 0022-3417
Garcia E, Lightley J, Kumar S, et al., 2021, Application of direct stochastic optical reconstruction microscopy (dSTORM) to the histological analysis of human glomerular disease, JOURNAL OF PATHOLOGY CLINICAL RESEARCH, Vol: 7, Pages: 438-445
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Medjeral-Thomas NR, Cook HT, Pickering MC, 2021, Complement activation in IgA nephropathy, Springer Seminars in Immunopathology, Vol: 43, Pages: 679-690, ISSN: 1863-2297
IgA nephropathy pathogenesis is incompletely understood, and this limits the development of disease-specific biomarkers and effective therapies. Evidence of complement activity in IgA nephropathy is well established. However, a growing body of research indicates complement activity is an important contributor to IgA nephropathy pathology. In particular, multiple associations have been identified between complement alternative, lectin and terminal pathway proteins and IgA nephropathy severity. Recently, we have also gained insight into possible mechanisms that could link glomerular IgA deposition, complement activity, glomerular inflammation and disease severity. Ongoing clinical trials of therapeutic complement inhibitors will provide insight into the importance of complement activity to IgA nephropathy pathogenesis. Further research into mechanisms of complement activity is essential to improving our understanding and management of patients with IgA nephropathy.
Kousios A, Mcadoo S, Blakey S, et al., 2021, Masked crystalline light chain tubulopathy and podocytopathy with focal segmental glomerulosclerosis: a rare MGRS-associated renal lesion, Histopathology, Vol: 79, Pages: 265-268, ISSN: 1365-2559
Monoclonal Gammopathy of Renal Significance (MGRS) encompasses a wide spectrum of histopathology. Characterizing rare forms of MGRS-related renal pathology remains work in progress. Light chain crystalline podocytopathy in the context of MGRS, either in isolation or combined with proximal tubulopathy (LCPT) has rarely been described. Unravelling MGRS pathologies is critical for patient management and often requires ancillary techniques for antigen retrieval to demonstrate light chain (LC) restriction on immunofluorescence (IF).
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