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Complement factor and iga nephropathy

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https://www.readbyqxmd.com/read/30298653/complement-in-glomerular-diseases
#1
REVIEW
Ying Tan, Ming-Hui Zhao
Complement activation has been identified to play a vital role in the pathogenesis of many glomerulonephritis, either as direct complement activation-driven factor in thrombotic microangiopathy and C3 glomerulopathy, and/or as an important contributor in lupus nephritis and anti-neutrophil cytoplasmic antibody-associated vasculitis. Recent studies indicated that complement activation may also play roles in the pathogenesis of immunoglobulin A nephropathy and focal segmental glomerulosclerosis. Interestingly, monoclonal immunoglobulins/light chains from patients with monoclonal gammopathy may interfere with complement activation and thus indirectly result in complement-mediated glomerulonephritis...
October 2018: Nephrology
https://www.readbyqxmd.com/read/30219152/coding-and-noncoding-variants-in-cfh-act-synergistically-for-complement-activation-in-immunoglobulin-a-nephropathy
#2
Wei-Yi Guo, Qing-Zhen Liu, Li Zhu, Zeng-Yan Li, Si-Jun Meng, Su-Fang Shi, Li-Jun Liu, Ji-Cheng Lv, Ping Hou, Hong Zhang
BACKGROUND: In immunoglobulin A nephropathy (IgAN), complement activation occurs in both the systemic circulation and in situ (glomerular). A recent IgAN-genome-wide association study (GWAS) identified 1q32 as an IgAN susceptible locus that contained the complement regulatory protein coding gene complement factor H (CFH). Here, we explored the combined genetic effects of coding and noncoding variants in CFH, rs6677604 and rs800292 on complement activation in IgAN. METHODS: In total, 1,194 IgAN patients and 900 healthy controls who were the same as the Beijing Discovery Cohort in our recent IgAN-GWAS were recruited...
August 2018: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/30141239/high-levels-of-urinary-complement-proteins-are-associated-with-chronic-renal-damage-and-proximal-tubule-dysfunction-in-iga-nephropathy
#3
Lu Wen, Zhanzheng Zhao, Zheng Wang, Jing Xiao, Henrik Birn, Jon Waarst Gregersen
AIM: Complement activation is involved in the pathogenesis and progression of IgA nephropathy (IgAN); however, the clinical implication of abnormal complement protein levels in serum and urine is not clear. To address this we analysed the correlation between disease activity and complement proteins in serum and urine from IgAN patients, and compared to patients with other types of chronic kidney disease (CKD) as well as healthy controls. METHODS: We included 85 Chinese patients with IgAN, 23 patients with non-proliferative CKD, and 20 healthy individuals...
August 23, 2018: Nephrology
https://www.readbyqxmd.com/read/30050540/self-damage-caused-by-dysregulation-of-the-complement-alternative-pathway-relevance-of-the-factor-h-protein-family
#4
REVIEW
Pilar Sánchez-Corral, Richard B Pouw, Margarita López-Trascasa, Mihály Józsi
The alternative pathway is a continuously active surveillance arm of the complement system, and it can also enhance complement activation initiated by the classical and the lectin pathways. Various membrane-bound and plasma regulatory proteins control the activation of the potentially deleterious complement system. Among the regulators, the plasma glycoprotein factor H (FH) is the main inhibitor of the alternative pathway and its powerful amplification loop. FH belongs to a protein family that also includes FH-like protein 1 and five factor H-related (FHR-1 to FHR-5) proteins...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29969623/clinical-and-prognostic-significance-of-glomerular-c1q-deposits-in-primary-mn
#5
Mu-Fan Zhang, Zhao Cui, Yi-Miao Zhang, Zhen Qu, Xin Wang, Fang Wang, Li-Qiang Meng, Xu-Yang Cheng, Gang Liu, Ming-Hui Zhao
BACKGROUND: Although complement activation is believed to be important in mediating PMN, the pathways involved and clinical consequences remain controversial. Many cases of idiopathic or primary membranous nephropathy (PMN) present with subepithelial C1q deposits along with IgG and C3 on glomerular capillary walls but without deposits of IgA or IgM ("full house") by immunofluorescence or any causes of secondary MN. We sought to define the clinical and pathological significance of these C1q deposits in PMN by comparing a variety of clinical parameters, outcomes and other serum and urine factors in patients with and without significant glomerular C1q deposits...
October 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29946875/-pathophysiology-and-treatment-of-iga-nephropathy
#6
REVIEW
R Bollin, H Haller
The IgA nephropathy is the most frequent form of glomerulonephritis worldwide. In approximately 30% of patients a reduction in the glomerular filtration rate of approximately 50% is observed within 10 years. Patients with IgA nephropathy form IgG autoantibodies against galactose-deficient IgA1 antibodies. This results in deposition of these antibodies in the mesangium and activation of complement with mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis and atrophying interstitial fibrosis...
July 2018: Der Internist
https://www.readbyqxmd.com/read/29933843/iga-nephropathy-new-insights-into-the-role-of-complement
#7
Jürgen Floege, Mohamed R Daha
Glomerular complement deposition is common in IgA nephropathy, and recent genome-wide association studies point to a role of complement factor H and complement factor H-related proteins in disease susceptibility. A number of recent studies have now documented elevated levels of some factor H-related proteins in IgA nephropathy, which might contribute to enhanced complement activation.
July 2018: Kidney International
https://www.readbyqxmd.com/read/29759419/circulating-complement-factor-h-related-protein-5-levels-contribute-to-development-and-progression-of-iga-nephropathy
#8
Li Zhu, Wei-Yi Guo, Su-Fang Shi, Li-Jun Liu, Ji-Cheng Lv, Nicholas R Medjeral-Thomas, Hannah J Lomax-Browne, Matthew C Pickering, Hong Zhang
IgA nephropathy (IgAN) is a disease associated with activation of the complement system. But the factors influencing complement activation in IgAN are not fully understood. Complement factor H (FH) is an essential negative regulator of complement C3 activation. Complement factor H-related protein (FHR)-5 shares high sequence similarity with factor H. However, unlike factor H, on binding to activated C3 it enables further activation to proceed. Previously, we reported the contribution of rare variants of the CFHR5 gene to IgAN susceptibility...
July 2018: Kidney International
https://www.readbyqxmd.com/read/29725647/progressive-iga-nephropathy-is-associated-with-low-circulating-mannan-binding-lectin-associated-serine-protease-3-masp-3-and-increased-glomerular-factor-h-related-protein-5-fhr5-deposition
#9
Nicholas R Medjeral-Thomas, Anne Troldborg, Nicholas Constantinou, Hannah J Lomax-Browne, Annette G Hansen, Michelle Willicombe, Charles D Pusey, H Terence Cook, Steffen Thiel, Matthew C Pickering
Introduction: IgA nephropathy (IgAN) is characterized by glomerular deposition of galactose-deficient IgA1 and complement proteins and leads to renal impairment. Complement deposition through the alternative and lectin activation pathways is associated with renal injury. Methods: To elucidate the contribution of the lectin pathway to IgAN, we measured the 11 plasma lectin pathway components in a well-characterized cohort of patients with IgAN. Results: M-ficolin, L-ficolin, mannan-binding lectin (MBL)-associated serine protease (MASP)-1 and MBL-associated protein (MAp) 19 were increased, whereas plasma MASP-3 levels were decreased in patients with IgAN compared with healthy controls...
March 2018: KI Reports
https://www.readbyqxmd.com/read/29606258/treatment-of-iga-nephropathy-recent-advances-and-prospects
#10
REVIEW
Rosanna Coppo
IgA nephropathy, identified 50 years ago in France, is the most frequent glomerular disease worldwide. The course is variable, but in most of the cases there is a relentless decline in renal function, reaching end-stage renal failure in 10-60% of the cases after 10 years and in 40% after 20 years. These data justify the interest for finding a suitable therapeutic approach particularly in progressive cases. A supportive care, including renin-angiotensin system inhibitors is the priority in cases with slowly declining renal function, particularly when developing proteinuria...
April 2018: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/29241200/atypical-hemolytic-uremic-syndrome-associated-with-complement-factor-h-mutation-and-iga-nephropathy-a-case-report-successfully-treated-with-eculizumab
#11
Hironori Nakamura, Mariko Anayama, Mutsuki Makino, Yasushi Makino, Katsuhiko Tamura, Masaki Nagasawa
We present a rare case of IgA nephropathy in a patient who developed atypical hemolytic uremic syndrome (aHUS) associated with a complement factor H (CFH) gene mutation, and who was successfully treated with eculizmab. A 76-year-old man was admitted as the patients had thrombotic microangiopathies findings. The patient was treated with plasma exchange, hemodialysis and methylprednisolone. A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 level was not decreased. Light microscopy findings were consistent with hemolytic uremic syndrome and immunofluorescence analysis revealed IgA and C3 were detected...
2018: Nephron
https://www.readbyqxmd.com/read/29240274/complement-factor-h-gene-polymorphism-rs6677604-and-the-risk-severity-and-progression-of-iga-nephropathy-a-systematic-review-and-meta-analysis
#12
See Cheng Yeo, Xinyang Liu, Adrian Liew
BACKGROUND & AIM: Complement activation plays a key role in the pathogenesis of IgA nephropathy (IgAN). Several studies have reported an association between complement factor H gene rs6677604 polymorphism and susceptibility to IgAN; however, attempts at validating this relationship had yielded inconsistent results. We performed a systematic review and meta-analysis to clarify the association between rs6677604 and IgAN susceptibility, disease severity and chronic progression. METHODS: A comprehensive database search was performed to identify eligible studies...
December 14, 2017: Nephrology
https://www.readbyqxmd.com/read/29114042/deletion-variants-of-cfhr1-and-cfhr3-associate-with-mesangial-immune-deposits-but-not-with-progression-of-iga-nephropathy
#13
Perrine Jullien, Blandine Laurent, Guillaume Claisse, Ingrid Masson, Miriana Dinic, Damien Thibaudin, Francois Berthoux, Eric Alamartine, Christophe Mariat, Nicolas Maillard
Activation of complement through the alternative pathway has a key role in the pathogenesis of IgA nephropathy (IgAN). Large, international, genome-wide association studies have shown that deletion of complement factor H-related genes 1 and 3 ( CFHR3,1Δ ) is associated with a reduced risk of developing IgAN, although the prognostic value of these deletions in IgAN remains unknown. Here, we compared the renal outcomes of patients with IgAN according to their CFHR3,1Δ genotype. This retrospective, monocentric cohort study included 639 white patients with biopsy-proven IgAN since 1979 (mean age at diagnosis, 40...
February 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29092674/autoantibodies-against-complement-components-in-systemic-lupus-erythematosus-role-in-the-pathogenesis-and-clinical-manifestations
#14
M H Hristova, V S Stoyanova
Many complement structures and a number of additional factors, i.e. autoantibodies, receptors, hormones and cytokines, are implicated in the complex pathogenesis of systemic lupus erythematosus. Genetic defects in the complement as well as functional deficiency due to antibodies against its components lead to different pathological conditions, usually clinically presented. Among them hypocomplementemic urticarial vasculitis, different types of glomerulonephritis as dense deposit disease, IgA nephropathy, atypical haemolytic uremic syndrome and lupus nephritis are very common...
December 2017: Lupus
https://www.readbyqxmd.com/read/29037908/new-insights-in-the-pathogenesis-of-immunoglobulin-a-vasculitis-henoch-sch%C3%A3-nlein-purpura
#15
REVIEW
Marieke H Heineke, Aranka V Ballering, Agnès Jamin, Sanae Ben Mkaddem, Renato C Monteiro, Marjolein Van Egmond
Immunoglobulin A vasculitis (IgAV), also referred to as Henoch-Schönlein purpura, is the most common form of childhood vasculitis. The pathogenesis of IgAV is still largely unknown. The disease is characterized by IgA1-immune deposits, complement factors and neutrophil infiltration, which is accompanied with vascular inflammation. Incidence of IgAV is twice as high during fall and winter, suggesting an environmental trigger associated to climate. Symptoms can resolve without intervention, but some patients develop glomerulonephritis with features similar to IgA nephropathy that include hematuria, proteinuria and IgA deposition in the glomerulus...
December 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28938951/complement-factor-h-related-proteins-in-iga-nephropathy-sometimes-a-gentle-nudge-does-the-trick
#16
COMMENT
Joshua M Thurman, Jennifer Laskowski
Complement activation probably contributes to glomerular inflammation and damage in IgA nephropathy. In this issue, 2 groups report that levels of factor H-related protein 1 are elevated in patients with IgA nephropathy and correlate with disease progression. These studies provide new evidence that the complement cascade is important to the pathogenesis of this disease. These results also suggest that factor H-related protein 1 levels may be useful for identifying those patients at high risk of disease progression...
October 2017: Kidney International
https://www.readbyqxmd.com/read/28915952/iga-nephropathy-during-treatment-with-tnf-alpha-blockers-could-it-be-predicted
#17
Vito Di Lernia
Immunoglobulin A (IgA) nephropathy (IgAN) may sometimes be related to exposure to pharmacological agents, among which anti-Tumor Necrosis Factor (TNF)-alpha agents. The characteristic pathological feature is a deposition of IgA-containing immune complexes in vessel walls in the kidney mesangium. The link between TNF-alpha blockers and IgAN may be hypothesized examining diseases which share pathologic features. In this respect, idiopathic IgAN and Henoch Schonlein Purpura have been the object of studies revealing a pathogenetic role of aberrant glycosylation of IgA1 molecules...
September 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28673452/circulating-complement-factor-h-related-proteins-1-and-5-correlate-with-disease-activity-in-iga-nephropathy
#18
Nicholas R Medjeral-Thomas, Hannah J Lomax-Browne, Hannah Beckwith, Michelle Willicombe, Adam G McLean, Paul Brookes, Charles D Pusey, Mario Falchi, H Terence Cook, Matthew C Pickering
IgA nephropathy (IgAN) is a common cause of chronic kidney disease and end-stage renal failure, especially in young people. Due to a wide range of clinical outcomes and difficulty in predicting response to immunosuppression, we need to understand why and identify which patients with IgAN will develop progressive renal impairment. A deletion polymorphism affecting the genes encoding the complement factor H-related protein (FHR)-1 and FHR-3 is robustly associated with protection against IgAN. Some FHR proteins, including FHR-1 and FHR-5, antagonize the ability of complement factor H (fH), the major negative regulator of the complement alternative pathway, to inhibit complement activation on surfaces, a process termed fH deregulation...
October 2017: Kidney International
https://www.readbyqxmd.com/read/28637589/elevated-factor-h-related-protein-1-and-factor-h-pathogenic-variants-decrease-complement-regulation-in-iga-nephropathy
#19
COMPARATIVE STUDY
Agustín Tortajada, Eduardo Gutiérrez, Elena Goicoechea de Jorge, Jaouad Anter, Alfons Segarra, Mario Espinosa, Miquel Blasco, Elena Roman, Helena Marco, Luis F Quintana, Josué Gutiérrez, Sheila Pinto, Margarita Lopez-Trascasa, Manuel Praga, Santiago Rodriguez de Córdoba
IgA nephropathy (IgAN), a frequent cause of chronic kidney disease worldwide, is characterized by mesangial deposition of galactose-deficient IgA1-containing immune complexes. Complement involvement in IgAN pathogenesis is suggested by the glomerular deposition of complement components and the strong protection from IgAN development conferred by the deletion of the CFHR3 and CFHR1 genes (ΔCFHR3-CFHR1 ). Here we searched for correlations between clinical progression and levels of factor H (FH) and FH-related protein 1 (FHR-1) using well-characterized patient cohorts consisting of 112 patients with IgAN, 46 with non-complement-related autosomal dominant polycystic kidney disease (ADPKD), and 76 control individuals...
October 2017: Kidney International
https://www.readbyqxmd.com/read/28166191/decreased-serum-c3-levels-in-immunoglobulin-a-iga-nephropathy-with-chronic-kidney-disease-a-propensity-score-matching-study
#20
Xi Yang, Ri-Bao Wei, Yang Wang, Ting-Yu Su, Qing-Ping Li, Ting Yang, Meng-Jie Huang, Kun-Ying Li, Xiang-Mei Chen
BACKGROUND The effects of low serum C3 levels and the activation of the complement system on the development and the prognosis of IgAN are unclear. The present study aimed to determine whether decreased levels of complement C3 influence the prognosis of IgAN patients with chronic kidney disease. MATERIAL AND METHODS We enrolled a total of 1564 patients with primary IgAN diagnosed by renal biopsy at the Chinese PLA General Hospital from January 2011 to March 2015. The endpoint was end-stage renal disease (ESRD) or a doubling of the baseline serum creatinine (D-SCr) level...
February 6, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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