IgA Deposits Research Articles

Rutin reduces inflammation and fibrosis via TGF-β/SMAD pathways in IgA nephropathy induced rats.

Rutin is a flavonoid glycoside obtained from the plant Ruta graveolens. It was known to have immunosuppressant activities. This study was focused on effect of rutin against immunoglobulin A (IgA) nephropathy. IgA nephropathy was induced in Sprague-Dawley rats with various inducing agents described in text. During the later part of the induction phase, rutin was administered. Control group rats did not receive any treatment or inducing agent, induced group rats received only the inducing agents, whereas treatment group received the inducing agents as well as rutin. During the study, various biochemical parameters pertaining to kidney function were evaluated and also, the expression of proteins and cytokines responsible for inflammation and fibrosis were assessed. The effect of rutin in IgA nephropathy was promising as treatment with rutin reduced the deposition of IgA in the glomeruli of rats. Along with this we also tried to establish the probable mechanism of action of rutin and based on the summary of the results it was concluded that rutin reduced the inflammation and fibrosis related to IgA nephropathy by inhibiting the TGF-β/SMAD pathways and ultimately reducing the expression of α-smooth muscle actin (α-SMA). Comprehending all the above consideration, it may be safely said that that rutin alleviated inflammation and also fibrosis mediated by IgA, by suppressing the transforming growth factor-β (TGF-β) activities through suppressor of mothers against decapentaplegic pathways and reduced the epithelial-to-mesenchymal transition by downregulating the α-SMA which is a marker for fibrosis.

Clinicopathological Features of Membranous Nephropathy Complicated by IgA Nephropathy: A Retrospective Analysis of Seven Cases.

Aims/Background Both membranous nephropathy (MN) and immunoglobulin A nephropathy (IgAN) are immune complex-mediated glomerular diseases, but the concurrent occurrence of these two conditions in the same patient is not common, a phenomenon that is currently not supported by clinical data in terms of treatment and prognosis. This study explores the clinical and pathological characteristics, as well as the treatment outcomes, of patients affected by MN and IgAN simultaneously. Methods The clinical data, pathological features, and diagnostic and therapeutic information of seven cases of MN complicated by IgAN, treated between December 2015 and December 2022, were retrospectively analyzed. Results Among the seven cases, there were two male and five female patients, with an average age of 57.3 ± 9.2 years. All patients presented with clinical manifestations of proteinuria and edema upon admission, with an average 24-hour urine protein of 3716.6 ± 1519.4 mg/24 h. Phospholipase A2 receptor (PLA2R) expression was detected in all seven cases, and nephrotic syndrome was clinically diagnosed in five cases. Additionally, all seven cases showed microscopic hematuria, with intermittent gross hematuria in two cases. All seven patients included in this study underwent renal biopsy. After disease staging, the patients had MN stages I-III and IgAN stages II-III. Pathological findings revealed abnormal glomerular basement membrane (GBM) and diffuse immunoglobulin G (IgG) deposition in the subepithelial space, predominantly of the IgG4 subtype. Simultaneously, there was diffuse mesangial zone deposition of immunoglobulin A (IgA) to varying degrees, co-localization of complement component C3 and IgA, and mesangial cell proliferation. Treatment strategies included angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in combination with steroids or immunosuppressive therapies such as tacrolimus, cyclophosphamide, and rituximab. After 2-6 months of treatment, all patients achieved complete remission with a favourable prognosis. Conclusion MN accompanied by IgAN tends to occur more frequently in middle-aged and elderly individuals, with a relatively low incidence. The latent feature of the comorbidities manifests as a form of IgAN superimposed on the background of MN. Utilizing ACEI or ARB in combination with steroids or various immunosuppressive therapies represents a potentially effective treatment strategy.

Combination treatment with telitacicept, mycophenolate mofetil and glucocorticoids for immunoglobulin A nephropathy: A case report

BACKGROUND Telitacicept reduces B cell activation and abnormal immunoglobulin A (IgA) antibody production by inhibiting the activity of B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), thereby decreasing IgA deposition in the glomeruli and local inflammatory response. This ultimately protects the kidneys from damage. This mechanism suggests that Telitacicept has potential efficacy in the treatment of IgA nephropathy. CASE SUMMARY We present the case of a 24-year-old female who was diagnosed with IgA nephropathy due to significant proteinuria and mild renal impairment. Pathologically, she exhibited focal proliferative glomerulonephritis. Treatment with angiotensin II receptor blocker, hormones, and mycophenolate mofetil did not lead to a significant improvement in her condition. However, upon the addition of telitacicept, the patient’s renal function recovered and her proteinuria rapidly reduced. Hormones were swiftly tapered and discontinued, with no occurrence of severe infections or related complications. CONCLUSION Telitacicept combined with hormones and mycophenolate mofetil may be a safe and effective induction therapy for IgA nephropathy.

Monoclonal Membranous Glomerulopathy in a Patient with Positive Serology for Lupus Nephritis

Abstract Introduction/Objective Monoclonal membranous glomerulopathy (M-MGN) is a rare entity; only two reports are available in the literature. Monoclonal membranous glomerulopathy has been called either monoclonal immunoglobulin deposition disease associated with membranous features in a 3-patient small series report or membranous glomerulopathy with light chain restriction in another larger series with 28 cases. We report M-MGN in a patient with positive serology lupus. Methods/Case Report The patient was a 74-year-old man with hypertension and nephrotic range proteinuria (protein/creatinine ratio at 8.5). His serum creatinine remained normal at 0.6 mg/dL. The patient was positive for double-stranded DNA and ANA at low titer, but had reduced complement C3 and C4. Immunofixation was negative for monoclonal protein. The light microscopy of the renal biopsy revealed thickened loops of glomeruli with mild interstitial nephritis. Immunofluorescent studies showed a positive linear/granular pattern of IgG and lambda but negative kappa staining along the glomerular loops. Electron microscopy revealed smooth contoured stage 2 subepithelial deposits. An outside consultation confirmed our diagnosis and found IgG2 restriction in glomeruli. Electrophoresis revealed no monoclonal protein in the serum. Results (if a Case Study enter NA) NA Conclusion Our patient demonstrated M-MGN with mild interstitial nephritis; the latter may be related to his lupus status. As 30% of patients with M-MGN have either monoclonal serology or B-cell lymphoproliferative disorders, with most having a restricted IgG subtyping, a close follow-up and even chemotherapy for a B-cell clone should be considered.

A case of de novo glomerulonephritis following COVID-19 in a patient with preexistent IgA vasculitis.

During the unprecedented COVID-19 outbreak, new-onset or relapsing glomerulonephritis, such as ANCA-associated glomerulonephritis and Immunoglobulin A (IgA) nephropathy, following COVID-19 has been reported. However, to date, the association of COVID-19 with preexistent IgA vasculitis (IgAV) remains unclear. Here, we present the case of a 20-something old Japanese woman with preexistent IgAV who newly developed glomerulonephritis following COVID-19. At the diagnosis of IgAV, she had cutaneous purpura, joint pains, and gastrointestinal symptoms, but no signs of kidney involvement. Three months ago, she was tested positive for COVID-19 and subsequently developed hematuria and proteinuria. She was then admitted to our hospital and renal biopsy showed glomerular mesangial expansion and hypercellularity and cellular and fibrocellular crescents, accompanied by diffuse IgA and C3 deposits. With the diagnosis of de novo IgAV nephritis, the patient was treated with intravenous methylprednisolone followed by oral prednisolone. She had favorable responses to this treatment and has achieved and maintained the remission of hematuria and proteinuria after initiation of glucocorticoid therapy. Our case highlights that immune response to SARS-CoV-2 infection could trigger the onset of glomerulonephritis in the IgAV patients who have no renal involvement.

Immunoglobulin A-dominant membranoproliferative glomerulonephritis-like pattern of injury as a possible paraneoplastic nephropathy in a breast cancer patient.

A middle-aged woman was found to have proteinuria during a health check-up. About sixteen months later, she was diagnosed with stage IIA invasive ductal carcinoma of the right breast. Her proteinuria progressed to nephrotic syndrome with significant hematuria. Hormone therapy was initiated for her estrogen and progesterone receptor-positive breast cancer. A kidney biopsy performed 47days after starting the therapy revealed an IgA-dominant membranoproliferative glomerulonephritis-like pattern of injury. Electron microscopy showed subendothelial-dominant electron-dense deposits (EDD), with small amounts of mesangial EDD and a single occurrence of subepithelial hump-like EDD, along with occasional mesangial interpositions. Similar pathology can be caused by IgA vasculitis with nephritis, IgA-dominant infection-associated glomerulonephritis, and liver disease-associated glomerulopathy, but all of these were ruled out. The deposited IgA was found to be galactose-deficient IgA1. Thus, IgA nephropathy with glomerular capillary IgA deposition was considered. She underwent a right partial mastectomy and sentinel lymph node biopsy in the right axilla 75days after starting hormone therapy, followed by adjuvant radiation. Proteinuria and hematuria tended to decrease after the treatment, and this trend continued even after corticosteroid therapy for glomerulonephritis, which was administered 156days after starting hormone therapy. Approximately 15months after starting hormone therapy, her proteinuria had reduced to around 1.0g/g of creatinine, and her hematuria was negative. IgA nephropathy with glomerular capillary IgA deposition is known to be resistant to corticosteroid therapy. The favorable clinical course of the rare glomerulopathy following breast cancer treatment suggested a diagnosis of paraneoplastic glomerulopathy secondary to breast cancer in our patient.

Single-Cell Transcriptome Sequencing Identifies New Molecular Markers for Pathogenicity of IgA Deposition in the Mesangial Region

Single-Cell Transcriptome Sequencing Identifies New Molecular Markers for Pathogenicity of IgA Deposition in the Mesangial Region

Integrative Multi-Omics and Network Pharmacology Reveal the Mechanisms of Fangji Huangqi Decoction in Treating IgA Nephropathy

Ethnopharmacological relevanceFangji Huangqi Decoction (FJHQD), a classical Chinese herbal formulation, has demonstrated significant clinical efficacy in the treatment of IgA nephropathy (IgAN), although its mechanisms remain poorly understood. Aim of the studyThis study aims to investigate the renal protective mechanisms of FJHQD using an integrated approach that combines transcriptomics, proteomics, and network pharmacology. MethodsRenal glomerular structure changes were assessed via hematoxylin and eosin (H&E) and Masson staining. IgA expression in the glomeruli was quantified using immunofluorescence. Furthermore, the potential mechanisms underlying the effects of FJHQD were explored through a combined strategy of network pharmacology, transcriptomics, and proteomics. The expression of signaling pathway-related proteins was detected using Western blot. ResultsFJHQD inhibited mesangial cell proliferation and renal interstitial fibrosis, and significantly reduced excessive IgA deposition in the glomerular mesangium. Network pharmacology identified 113 important active components and 8 common active components in FJHQD, with quercetin, isorhamnetin, jaranol, and kaempferol having the highest number of target interactions. Integration of network pharmacology with multi-omics approaches revealed that 44 active components regulated numerous immune and inflammatory signaling pathways through 17 hub targets. These pathways include the Calcium signaling pathway, cAMP signaling pathway, Ras signaling pathway, MAPK signaling pathway, and PI3K-AKT signaling pathway. Subsequent in vivo experiments demonstrated that FJHQD effectively regulates the identified pathways in IgAN mice. Ultimately, molecular docking results further validated the reliability of the network pharmacology combined with multi-omics analyses. ConclusionThe findings suggest that FJHQD exerts a renal protective effect, potentially through modulation of the Calcium signaling pathway, cAMP signaling pathway, Ras signaling pathway, MAPK signaling pathway, and PI3K-AKT signaling pathway. These insights offer valuable support for the clinical use of FJHQD and open new avenues for exploring the active compounds and molecular mechanisms of Traditional Chinese Medicines (TCMs).

Profiles of IgA Deposition and Patterns in Kidney Diseases

Profiles of IgA Deposition and Patterns in Kidney Diseases

Renal Progenitor Cells Isolated from Urine of Patients with IgA Nephropathy Formed Renal Spheroids That Can Recapitulate Typical IgA1 Deposition

Renal Progenitor Cells Isolated from Urine of Patients with IgA Nephropathy Formed Renal Spheroids That Can Recapitulate Typical IgA1 Deposition

Dépôts tissulaires non amyloïdes d’immunoglobuline monoclonale (hors atteinte rénale)

Monoclonal immunoglobulins can form deposits other than amyloidosis in various tissues. Immunofluorescence is the key analysis for the identification of monoclonal immunoglobulin deposits. Pulmonary light chain deposition disease is a diagnosis to be considered when dealing with diffuse cystic lung disease.

Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits in a Patient with Recent Deceased Donor Kidney Transplant Successfully Treated with Rituximab Monotherapy

Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits in a Patient with Recent Deceased Donor Kidney Transplant Successfully Treated with Rituximab Monotherapy

Fabry Disease with Genetic Variants of Unknown Significance and Concomitant Immunoglobulin A Nephropathy

Introduction: The diagnosis of Fabry disease (FD) with genetic variants of unknown significance (VUSs) is relatively difficult. We explored patients with novel VUS variants and concomitant immunoglobulin A nephropathy (IgAN) to improve the understanding of VUS. Methods: The study retrospectively investigated patients with genetically confirmed FD. Probands with VUS were selected from the database of FD patients who underwent genetic analysis. Demographic, clinicopathological, and laboratory data from probands and family members were collected and analyzed. Results: Fourteen probands and their family members were included in the study. The probands were divided into group 1 (patients with VUS, n = 5) and group 2 (patients with pathologic/likely pathologic variants, n = 9). The group 1 included 2 missense mutations and 1 deletion mutation, while the group 2 included 6 missense mutations and 2 deletion mutations. There were no significant differences in gender, age, serum creatinine, eGFR, and proteinuria between the two groups. IgA deposition with myeloid bodies was found in all VUS patients. The cardiac involvement in group 2 was more severe than that in group 1. Seven families performed the pedigree analysis, and after the comprehensive evaluation, two GLA variants (c.479C>A, p.Ala160Asp; c.1032-1058 del, p.Ser345_Met353del) were upgraded from VUS to the likely pathogenic. Conclusion: The clinical manifestations of FD are heterogeneous. FD often coexists with nephrotic disorders, such as IgAN and MCD. Comprehensive evaluation, especially tissue-specific biopsy, is necessary for patients with GLA-VUSs. Two GLA variants (c.479C>A, p.Ala160Asp; c.1032-1058 del, p.Ser345_Met353del) were upgraded from VUS to the likely pathogenic after the comprehensive evaluation.

A unique and rare presentation of Henoch-Schonlein purpura: a case report

Henoch-Schönlein purpura (HSP), or IgA vasculitis, is a common small vessel vasculitis in children, typically presenting with palpable purpura, abdominal pain, arthritis, and renal involvement. However, atypical presentations can delay diagnosis and management. A 12-year-old girl presented with multiple episodes of loose stools and abdominal pain. The initial diagnosis focused on acute gastroenteritis, and she was treated symptomatically. Subsequently, she developed urticarial rashes with breathing difficulty, complicating the diagnosis. Despite symptomatic treatment, she experienced severe abdominal pain, hematemesis and melena. Further investigations revealed antral gastritis, duodenitis, and cystitis. On the 14th day of admission, the patient developed characteristic palpable purpura on the lower limbs. Skin biopsy confirmed leukocytoclastic vasculitis with IgA deposits, consistent with HSP. The patient recovered with supportive care and remained symptom-free on follow-up. This case underscores the importance of considering HSP in pediatric patients with atypical presentations, such as gastrointestinal symptoms and urticaria without initial purpura. Early recognition and appropriate management are essential to prevent complications and ensure favourable outcomes. The variability in HSP presentations necessitates a high index of suspicion for timely diagnosis and treatment.

Characterization of Porcine Immunoglobulin Deposition in Human Livers Recovered Using a Xenogeneic Cross-Circulation.

Characterization of Porcine Immunoglobulin Deposition in Human Livers Recovered Using a Xenogeneic Cross-Circulation.

Cytogenetic abnormality in non-systemic light chain amyloidosis monoclonal gammopathy of renal significance: A field needs to be explored.

The role of cytogenetic abnormalities in non-systemic light chain amyloidosis monoclonal gammopathy of renal significance diseases still needs to be clarified. Bhutani etal. present the results of a study investigating the underlying plasma cell cytogenetic abnormalities in monoclonal immunoglobulin deposition disease (MIDD). The results show that translocation (11;14) is a common abnormality in MIDD and affects the presentation and outcomes. Commentary on: Bhutani etal. Translocation (11;14) is a common cytogenetic abnormality in clonal plasma cells in monoclonal immunoglobulin deposition disease. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19748.

Proanthocyanidins alleviate Henoch-Schönlein purpura by mitigating inflammation and oxidative stress through regulation of the TLR4/MyD88/NF-κB pathway.

Investigate Proanthocyanidins (PCs) efficacy and mechanisms in treating Henoch-Schönlein purpura (HSP)-like rat models, focusing on inflammatory and oxidative stress (OS) responses. An HSP-like rat model was established using ovalbumin (OVA) injection, leading to symptoms mimicking HSP. The study measured inflammatory markers (IL-4, IL-17, TNF-α), OS markers (MDA, SOD, CAT), and assessed the TLR4/MyD88/NF-κB signaling pathway's involvement via histopathological and immunofluorescence analyses. PCs treatment significantly improved HSP-like symptoms, reduced inflammatory cell infiltration, and decreased IgA deposition in renal mesangial areas. Serum analyses revealed that PCs effectively lowered IL-4, IL-17, TNF-α, and MDA levels while increasing SOD and CAT levels (p<0.05). Crucially, PCs also downregulated TLR4, MyD88, and NF-κB expressions, highlighting the blockage of the TLR4-mediated signaling pathway as a key mechanism. PCs show promising therapeutic effects in HSP-like rats by mitigating inflammatory responses and oxidative damage, primarily through inhibiting the TLR4/MyD88/NF-κB pathway. These findings suggest PCs as a potential treatment avenue for HSP, warranting further investigation.

Mucosal targeting in IgA nephropathy targeting the gut associated lymphoid tissue.

IgA nephropathy is a mucosally driven disease and new therapeutic approaches are specifically targeting the mucosal production of IgA in the hope that this will lead to a reduction in circulating IgA immune complexes and mesangial IgA deposition. In this lecture, I discuss the rationale for targeting the mucosal immune system of the gut and the existing data from clinical trials supporting such an approach as a disease modifying treatment for IgA nephropathy.

Paraneoplastic pembigus: clinical and diagnostic features

Paraneoplastic pemphigus is an autoimmune dermatosis following against the background of neoplasia. It can occur before cancer is diagnosed, during or shortly after treatment, and even during remission of the underlying disease. Typically, paraneoplastic pemphigus only refers to the deposition of IgG. The article is devoted to paraneoplastic IgA/IgG pemphigus, which is one of the rare forms of paraneoplastic pemphigus in which deposition of IgA together with IgG is observed. We have described a clinical case of a patient who developed various rashes during the period of remission of chronic lymphocytic leukemia. Diagnosis of paraneoplastic IgA/IgG pemphigus based on clinical and anamnestic data, the results of a diagnostic skin biopsy, immunofluorescence test, consultation with a hematologist and lab tests. Difficulties in diagnosing paraneoplastic pemphigus are due to the polymorphism of rashes and the variety of clinical and laboratory parameters, which may depend on concomitant oncological pathology. A diagnostic search requires an assessment of the clinical picture of the disease, a carefully collected anamnesis, and a complete diagnostic algorithm for patients with bullous dermatoses.

C4d, rather than C3d and C5b-9, is associated with graft loss in recurrent IgA deposition after kidney transplantation.

Recurrent IgA deposition is common after kidney transplantation. However, it is difficult to define whether IgA deposition is innocuous or contributes to organ damage. Next, although complement is known to be involved in the pathogenesis of IgA nephropathy (IgAN), its involvement has not been studied systematically in kidney transplant recipients (KTR). KTR with biopsy-proven native IgAN who underwent kidney biopsy after transplantation between 1995 and 2020 were included. Recurrent IgA deposition was defined as IgA deposit in the glomerulus. Staining of complement factors C4d, C3d, and C5b-9 were quantitatively evaluated using ImageScope. Sixty-seven KTR (85% male, 46±13 years old, 12 [6-24] months after transplantation, 58% with indication biopsy) were included in the analyses. Of them, 25 (37%) had recurrent IgA deposition. There were no clinical differences between KTR with and without recurrent IgA deposition. C3d and C5b-9 were always present in biopsies with IgA deposition, while C4d was present in 48% of the biopsies. During a median follow-up of 9.6 [4.8-14] years, 18 (27%) KTR developed death-censored graft failure. Recurrent IgA deposition was not associated with graft failure. Of the evaluated complement factors, only C4d staining was associated with graft failure in KTR with recurrent IgA deposition (Hazard ratio = 2.55, 95% confidence interval = 1.07-6.03, p = 0.034). Recurrent IgA deposition was not associated with graft failure in itself. C4d, when present, is strongly associated with graft loss in KTR with recurrent IgA deposition, suggesting a pathogenic role for the lectin pathway in recurrent IgAN.