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Frontiers in Nephrology 2023Immunoglobulin A nephropathy (IgAN), characterized by mesangial deposition of galactose-deficient-IgA1 (Gd-IgA1), is the most common biopsy-proven primary... (Review)
Review
Immunoglobulin A nephropathy (IgAN), characterized by mesangial deposition of galactose-deficient-IgA1 (Gd-IgA1), is the most common biopsy-proven primary glomerulonephritis worldwide. Recently, an improved understanding of its underlying pathogenesis and the substantial risk of progression to kidney failure has emerged. The "four-hit hypothesis" of IgAN pathogenesis outlines a process that begins with elevated circulating levels of Gd-IgA1 that trigger autoantibody production. This results in the formation and deposition of immune complexes in the mesangium, leading to inflammation and kidney injury. Key mediators of the production of Gd-IgA1 and its corresponding autoantibodies are B-cell activating factor (BAFF), and A proliferation-inducing ligand (APRIL), each playing essential roles in the survival and maintenance of B cells and humoral immunity. Elevated serum levels of both BAFF and APRIL are observed in patients with IgAN and correlate with disease severity. This review explores the complex pathogenesis of IgAN, highlighting the pivotal roles of BAFF and APRIL in the interplay between mucosal hyper-responsiveness, B-cell activation, and the consequent overproduction of Gd-IgA1 and its autoantibodies that are key features in this disease. Finally, the potential therapeutic benefits of inhibiting BAFF and APRIL in IgAN, and a summary of recent clinical trial data, will be discussed.
PubMed: 38362118
DOI: 10.3389/fneph.2023.1346769 -
Life Science Alliance Apr 2024IgA nephropathy (IgAN) is caused by deposition of IgA in the glomerular mesangium. The mechanism of selective deposition and production of IgA is unclear; however, we...
IgA nephropathy (IgAN) is caused by deposition of IgA in the glomerular mesangium. The mechanism of selective deposition and production of IgA is unclear; however, we recently identified the involvement of IgA autoantibodies. Here, we show that CBX3 is another self-antigen for IgA in gddY mice, a spontaneous IgAN model, and in IgAN patients. A recombinant antibody derived from gddY mice bound to CBX3 expressed on the mesangial cell surface in vitro and to glomeruli in vivo. An elemental diet and antibiotic treatment decreased the levels of autoantibodies and IgAN symptoms in gddY mice. Serum IgA and the recombinant antibody from gddY mice also bound to oral bacteria of the mice and binding was competed with CBX3. One species of oral bacteria was markedly decreased in elemental diet-fed gddY mice and induced anti-CBX3 antibody in normal mice upon immunization. These data suggest that particular oral bacteria generate immune responses to produce IgA that cross-reacts with mesangial cells to initiate IgAN.
Topics: Humans; Mice; Animals; Glomerulonephritis, IGA; Glomerular Mesangium; Immunoglobulin A; Kidney Glomerulus; Autoantibodies; Chromosomal Proteins, Non-Histone
PubMed: 38331476
DOI: 10.26508/lsa.202402588 -
Poultry Science Apr 2024Goose astrovirus (GAstV)-2, a novel pathogen identified in 2018, mainly causes visceral gout in goslings, leading to approximately 50% mortality. At present, no...
Goose astrovirus (GAstV)-2, a novel pathogen identified in 2018, mainly causes visceral gout in goslings, leading to approximately 50% mortality. At present, no commercial veterinary products are available to prevent and treat the disease. Our previous studies showed that nitric oxide (NO) and inducible NO synthase (iNOS) were markedly higher in the kidney and spleen of goslings infected with GAstV-2, but their effects during GAstV-2 infection remain unclear. In the present study, goslings were intraperitoneally injected with aminoguanidine (AG)-an iNOS inhibitor-to examine the role of NO during GAstV-2 infection. AG significantly decreased the serum NO concentration and iNOS mRNA expression in the kidney. Moreover, AG reduced the mortality, serum uric acid and creatinine content, and urate deposition in visceral organs and joints. Histopathological analysis demonstrated that AG reduced renal tubular cell necrosis, inflammatory cell infiltration, glycogen deposition in glomerular mesangium, and interstitial fibrosis, suggesting alleviation of kidney lesions. Furthermore, AG decreased the expression of renal injury markers such as KIM-1 and desmin; inflammatory cytokine-related genes such as IL-1β, IL-8, and MMP-9; and autophagy-related genes and proteins such as LC3II, ATG5, and Beclin1. However, quantitative real-time PCR and immunohistochemistry showed that treatment with AG did not affect the kidney and liver viral load. These findings suggest that AG decreases the mortality rate and kidney lesions in goslings infected with GAstV-2 through mechanisms associated with autophagy and inhibition of inflammatory cytokine production in the kidney but not with GAstV-2 replication.
Topics: Animals; Geese; Uric Acid; Chickens; Astroviridae; Gout; Astroviridae Infections; Kidney; Cytokines; Avastrovirus; Guanidines
PubMed: 38306918
DOI: 10.1016/j.psj.2024.103484 -
Archives of Pathology & Laboratory... Jan 2024Galactose-deficient immunoglobulin A1 (Gd-IgA1) deposition in the renal mesangium plays a role in the pathogenesis of IgA nephropathy.
CONTEXT.—
Galactose-deficient immunoglobulin A1 (Gd-IgA1) deposition in the renal mesangium plays a role in the pathogenesis of IgA nephropathy.
OBJECTIVE.—
To assess the serum Gd-IgA1 level in biopsy-proven IgA nephropathy cases on diagnosis and 3 months post treatment and its relation with histologic Oxford classification.
DESIGN.—
In this hospital-based prospective cohort study, 40 cases and 20 controls were enrolled. Serum samples of biopsy-proven IgA nephropathy cases collected on the day of biopsy and 3 months post treatment were evaluated. Solid-phase ELISA (enzyme-linked immunosorbent assay) was performed for assessment of Gd-IgA1 level. All renal biopsies were scored by using Oxford Classification (C-MEST score). The association of serum Gd-IgA1 levels with other established prognostic parameters was assessed. To estimate the prognostic value of markers, logistic regression analysis and Kruskal-Wallis ANOVA (analysis of variance) were used.
RESULTS.—
Significant difference was observed in the serum Gd-IgA1 level values in the IgA nephropathy cases and healthy controls (P = .001) at baseline. However, no significant correlation between serum Gd-IgA1 levels at baseline and 3 months of follow-up (P = .31) or between baseline levels and age, proteinuria, hematuria, or estimated glomerular filtration rate was noted. There was no significant correlation between C-MEST score and serum Gd-IgA1 levels at baseline (P > .05); however, the distribution of Gd-IgA1 at 3 months was found to differ significantly between different grades of S score (P = .008).
CONCLUSIONS.—
Serum Gd-IgA1 levels may be of utility in predicting disease progression in IgA nephropathy cases. Measurement of serum Gd-IgA1 levels for the diagnosis and prognosis of IgA nephropathy may preclude the need for invasive renal biopsies.
PubMed: 38289288
DOI: 10.5858/arpa.2023-0190-OA -
Medical Science Monitor : International... Jan 2024The clinical association of purpura, arthralgia, and arthritis was first described in 1837 in a publication by Johann Lukas Schönlein, a German physician. In 1874,... (Review)
Review
The clinical association of purpura, arthralgia, and arthritis was first described in 1837 in a publication by Johann Lukas Schönlein, a German physician. In 1874, Eduard Henoch, a student of Schönlein, reported cases of children with purpura, abdominal pain, bloody diarrhea, and joint pain. IgA vasculitis, or Henoch-Schönlein purpura, is a systemic hypersensitivity vasculitis caused by the deposition of immune complexes in small blood vessels, including the renal glomeruli and mesangium. In the skin, the presentation is with non-thrombocytopenic purpura or urticaria. Worldwide, IgA nephropathy is the most common cause of primary glomerulonephritis. Detection of IgA deposition in small blood vessels and the renal glomeruli is diagnostic in most cases. This article aims to review the history, current classification, epidemiology, presentation, and diagnosis of IgA vasculitis and nephropathy, disease associations or trigger factors, including infections, vaccines, and therapeutic agents, and highlights some future approaches to improve diagnosis and clinical management.
Topics: Child; Humans; IgA Vasculitis; Immunoglobulin A; Glomerulonephritis, IGA; Vasculitis; Kidney Glomerulus; Hypersensitivity
PubMed: 38281080
DOI: 10.12659/MSM.943912 -
Cell Reports Feb 2024Recent regenerative studies using human pluripotent stem cells (hPSCs) have developed multiple kidney-lineage cells and organoids. However, to further form functional...
Recent regenerative studies using human pluripotent stem cells (hPSCs) have developed multiple kidney-lineage cells and organoids. However, to further form functional segments of the kidney, interactions of epithelial and interstitial cells are required. Here we describe a selective differentiation of renal interstitial progenitor-like cells (IPLCs) from human induced pluripotent stem cells (hiPSCs) by modifying our previous induction method for nephron progenitor cells (NPCs) and analyzing mouse embryonic interstitial progenitor cell (IPC) development. Our IPLCs combined with hiPSC-derived NPCs and nephric duct cells form nephrogenic niche- and mesangium-like structures in vitro. Furthermore, we successfully induce hiPSC-derived IPLCs to differentiate into mesangial and erythropoietin-producing cell lineages in vitro by screening differentiation-inducing factors and confirm that p38 MAPK, hypoxia, and VEGF signaling pathways are involved in the differentiation of mesangial-lineage cells. These findings indicate that our IPC-lineage induction method contributes to kidney regeneration and developmental research.
Topics: Humans; Animals; Mice; Induced Pluripotent Stem Cells; Kidney; Cell Lineage; Regeneration; Erythropoietin
PubMed: 38237600
DOI: 10.1016/j.celrep.2023.113602 -
AME Case Reports 2024Mesenteric cystic lymphatic malformation (LM) is a rare congenital benign malformation in adults, and its location in the mesentery of the sigmoid colon is even rarer.
BACKGROUND
Mesenteric cystic lymphatic malformation (LM) is a rare congenital benign malformation in adults, and its location in the mesentery of the sigmoid colon is even rarer.
CASE DESCRIPTION
We describe a rare case of LM of the mesentery in a 49-year-old woman. The patient was inadvertently identified during a physical examination 1 month earlier. Transvaginal ultrasound and magnetic resonance imaging (MRI) revealed the presence of an intrapelvic mass posterior to the uterus and right anterior to the sigmoid colon. According to the results of the ultrasound, the mass showed hypoechoic solid features with a blood flow signal, and MRI showed that the internal enhancement of the mass was uneven. According to its imaging characteristics, it was preliminarily speculated as a stromal tumor. The patient underwent laparoscopic fenestration and drainage of a sigmoid mesocolic cyst. The patient underwent laparoscopic fenestration and drainage of the sigmoid mesocolic cyst. The pathological diagnosis was cystic lymphangioma of the sigmoid mesangium. After the operation, the patient recovered well without any complications. No recurrence was observed during the 3-month follow-up.
CONCLUSIONS
LM is a challenging and rare disease, and its diagnosis is difficult. However, the combination of imaging examination and endoscopic ultrasound (EUS) technology can significantly improve the accurate diagnosis rate of the disease. Complete resection is the best choice for definite diagnosis and prevention of recurrence. It has been proved that laparoscopic surgery is a safe and feasible method for the treatment of this disease.
PubMed: 38234359
DOI: 10.21037/acr-23-143 -
Indian Journal of Clinical Biochemistry... Jan 2024Amyloidosis is an infiltrative disease where amyloid fibrils get deposited in the organs like kidney, liver and spleen. Amyloid deposition in the kidneys classically...
UNLABELLED
Amyloidosis is an infiltrative disease where amyloid fibrils get deposited in the organs like kidney, liver and spleen. Amyloid deposition in the kidneys classically meant deposition in the glomeruli and mesangium until 2008 when interstitial amyloid deposits were isolated and named as` Leukocyte cell-derived chemotaxin 2-associated amyloidosis. It is a progressive disease which clinically manifests as slowly progressive renal dysfunction and/or proteinuria. Our case 34 year old renal transplant recipient underwent graft biopsy post transplantation which revealed interstitial LECT-2 amyloid deposits. Unfortunately, he developed page kidney post biopsy which was managed conservatively with percutaneous drainage.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s12291-022-01072-6.
PubMed: 38223013
DOI: 10.1007/s12291-022-01072-6 -
Kidney International Jan 2024Mesangial complement C3 deposits, reflecting alternative and possibly lectin pathway activation, are characteristic in biopsies of patients with IgA nephropathy (IgAN)....
Mesangial complement C3 deposits, reflecting alternative and possibly lectin pathway activation, are characteristic in biopsies of patients with IgA nephropathy (IgAN). A recent randomized controlled trial tested the efficacy and safety of iptacopan, a factor B inhibitor, in patients with IgAN. Iptacopan dose-dependently reduced proteinuria, and there was a pronounced decrease of urinary C5b-9. This offers the perspective of "personalizing" therapy, which would be a unique feature of this novel approach to IgAN. A phase III clinical trial (APPLAUSE-IgAN) is ongoing.
Topics: Humans; Glomerulonephritis, IGA; Complement Activation; Glomerular Mesangium; Biopsy; Complement Factor B
PubMed: 38182298
DOI: 10.1016/j.kint.2023.10.012 -
Aging Jan 2024Immunoglobulin A nephropathy (IgAN), one type of glomerulonephritis, displays the accumulation of glycosylated IgA in the mesangium. Studies have demonstrated that both... (Review)
Review
Immunoglobulin A nephropathy (IgAN), one type of glomerulonephritis, displays the accumulation of glycosylated IgA in the mesangium. Studies have demonstrated that both genetics and epigenetics play a pivotal role in the occurrence and progression of IgAN. Post-translational modification (PTM) has been revealed to critically participate in IgAN development and progression because PTM dysregulation results in impaired degradation of proteins that regulate IgAN pathogenesis. A growing number of studies identify that PTMs, including sialylation, o-glycosylation, galactosylation, phosphorylation, ubiquitination and deubiquitination, modulate the initiation and progression of IgAN. Hence, in this review, we discuss the functions and mechanisms of PTMs in regulation of IgAN. Moreover, we outline numerous compounds that govern PTMs and attenuate IgAN progression. Targeting PTMs might be a useful strategy to ameliorate IgAN.
Topics: Humans; Glomerulonephritis, IGA; Glycosylation; Phosphorylation; Protein Processing, Post-Translational
PubMed: 38175721
DOI: 10.18632/aging.205406