DOUBLE IMMUNOFLUORESCENCE STUDIES OF IMMUNOGLOBULINS, COMPLEMENT COMPONENTS AND THEIR CONTROL PROTEINS IN PATIENTS WITH IgA NEPHROPATHY

1982 ◽  
Vol 32 (2) ◽  
pp. 251-256
Author(s):  
Yasuhiko Tomino ◽  
Masayuki Endoh ◽  
Yasuo Nomoto ◽  
Hideto Sakai
Keyword(s):  
Iga Nephropathy ◽  
Double Immunofluorescence ◽  
Complement Components ◽  
Immunofluorescence Studies

scholarly journals History of IgA Nephropathy Mouse Models

2021 ◽  
Vol 10 (14) ◽  
pp. 3142
Author(s):  
Batoul Wehbi ◽  
Virginie Pascal ◽  
Lina Zawil ◽  
Michel Cogné ◽  
Jean-Claude Aldigier
Keyword(s):  
Iga Nephropathy ◽  
Small Animal ◽  
Experimental Models ◽  
Murine Models ◽  
Therapeutic Approaches ◽  
Complement Components ◽  
Simple Description ◽  
Primary Glomerulonephritis ◽  
History Of ◽  
Small Animal Models

IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world. It was first described in 1968 by Jean Berger and Nicole Hinglais as the presence of intercapillary deposits of IgA. Despite this simple description, patients with IgAN may present very broad clinical features ranging from the isolated presence of IgA in the mesangium without clinical or biological manifestations to rapidly progressive kidney failure. These features are associated with a variety of histological lesions, from the discrete thickening of the mesangial matrix to diffuse cell proliferation. Immunofluorescence on IgAN kidney specimens shows the isolated presence of IgA or its inconsistent association with IgG and complement components. This clinical heterogeneity of IgAN clearly echoes its complex and multifactorial pathophysiology in humans, inviting further analyses of its various aspects through the use of experimental models. Small-animal models of IgAN provide the most pertinent strategies for studying the multifactorial aspects of IgAN pathogenesis and progression. Although only primates have the IgA1 subclass, several murine models have been developed in which various aspects of immune responses are deregulated and which are useful in the understanding of IgAN physiopathology as well as in the assessment of IgAN therapeutic approaches. In this manuscript, we review all murine IgAN models developed since 1968 and discuss their remarkable contribution to understanding the disease.

Detection of IgAl-Dominant Immune Complexes in Peripheral Blood Polymorphonuclear Leukocytes by Double Immunofluorescence in Patients with IgA Nephropathy

Nephron ◽  
1984 ◽  
Vol 37 (2) ◽  
pp. 137-139 ◽  
Author(s):  
Yasuhiko Tomino ◽  
Masahiko Miura ◽  
Takao Suga ◽  
Masayuki Endoh ◽  
Yasuo Nomoto ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Immune Complexes ◽  
Peripheral Blood ◽  
Polymorphonuclear Leukocytes ◽  
Double Immunofluorescence

scholarly journals Complement components, proteolysis‑related, and cell communication‑related proteins detected in urine proteomics are associated with IgA nephropathy

2014 ◽  
Vol 124 (7-8) ◽  
pp. 380-386
Author(s):  
Krzysztof Mucha ◽  
Magdalena Bakun ◽  
Radosław Jaźwiec ◽  
Michał Dadlez ◽  
Michał Florczak ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Cell Communication ◽  
Complement Components ◽  
Urine Proteomics ◽  
Related Proteins

scholarly journals microRNA-630 Regulates Underglycosylated IgA1 Production in the Tonsils by Targeting TLR4 in IgA Nephropathy

2020 ◽  
Vol 11 ◽  
Author(s):  
Chan Liu ◽  
Mu-Yao Ye ◽  
Wen-Zhe Yan ◽  
Xiao-Fei Peng ◽  
Li-Yu He ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Immunohistochemical Analysis ◽  
Bioinformatic Analysis ◽  
Cell Culture Supernatant ◽  
Mechanism Study ◽  
Complement Components ◽  
Mesangial Area ◽  
Primary Glomerular Disease

IgA nephropathy (IgAN) is the most common primary glomerular disease. The characteristic pathology involves immune complexes formed by the deposition of IgA1 and underglycosylated IgA1 aggregates in the mesangial area, which may be accompanied by the deposition of IgG and/or IgM and complement components. However, the molecular mechanisms of IgAN remain unclear. In the present study, microarray analysis showed that the expression of microRNA-630 (miR-630) was significantly reduced in palatal tonsils from IgAN patients compared with chronic tonsillitis. Additionally, bioinformatic analysis showed that Toll-like receptor 4 (TLR4) was the predicted target gene of miR-630 and was regulated by miR-630. When miR-630 was overexpressed in palatal tonsil mononuclear cells from IgAN patients, the expression of TLR4 was reduced and the content of IgA1 in the cell culture supernatant was decreased, and the level of galactosylation in the IgA1 hinge region was increased. Moreover, immunohistochemical analysis showed that the expression of TLR4 in IgAN patients was significantly increased. After knocking down the expression of TLR4, both the concentration of IgA1 and the binding force of IgA1 with broad bean lectin were significantly reduced in IgAN. Furthermore, the mechanism study demonstrated that TLR4 might regulate the expression of IL-1β and IL-8 through NF-κB signaling pathway to modulate the concentration of IgA1 and the glycosylation level of IgA1. This interesting finding may offer new insight into the molecular mechanism of IgAN.

Coexpression and Accumulation of Ubiquitin +1 and ZZ Proteins in Livers of Children with α1-Antitrypsin Deficiency

2002 ◽  
Vol 5 (3) ◽  
pp. 293-298 ◽  
Author(s):  
Sandy S. Wu ◽  
Jean-Pierre de Chadarevian ◽  
Laron McPhaul ◽  
Nora E. Riley ◽  
Fred W. van Leeuwen ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Polyclonal Antibodies ◽  
Genomic Information ◽  
Double Immunofluorescence ◽  
Mutant Proteins ◽  
Explanted Liver ◽  
Immunofluorescence Studies ◽  
Antitrypsin Deficiency ◽  
Pathologic Processes ◽  
Sectioned Tissue

The ZZ variant of α1-antitrypsin deficiency (AATD) is well known to cause liver damage and cirrhosis in some affected children. Ubiquitin abnormality was recently shown to be significant in AATD in childhood cirrhosis. Molecular misreading (MM), defined as faulty transcription of genomic information from DNA into mRNA, as well as its translation into mutant proteins, has been documented in many pathologic processes where aggregation of abnormal proteins occurs. The misread protein, ubiquitin-B+1 (UBB+1), was recently identified in the hallmarks of various neurological disorders. The objective of this study was to determine whether MM of ubiquitin occurs in AATD. Twelve explanted liver specimens from AATD-affected children with cirrhosis were retrieved from archival sources, along with 10 control liver specimens obtained from autopsies of age-matched children with no clinical, gross anatomic, or histologic evidence of liver disease. Double immunofluorescence studies using rabbit polyclonal antibodies against UBB+1 and AAT were performed on consecutively sectioned tissue. UBB+1 immunoreactivity was colocalized with AAT in all cirrhotic AATD livers. The control livers were consistently negative. Ubiquitin MM is prominent in AATD-affected cirrhotic livers. This indicates that for children with AATD and cirrhosis, ubiquitin MM is a necessary cofactor to the aggregation of mutant ZZ isoform of AATD.

Double immunofluorescence studies of glomerular sialic acids in patients with diabetic nephropathy

1987 ◽  
Vol 1 (2) ◽  
pp. 61-64 ◽  
Author(s):  
Yasuhiko Tomino ◽  
Mitsunori Yagame ◽  
Wataru Inoue ◽  
Seiichi Watanabe ◽  
Hideaki Kaneshige ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Sialic Acids ◽  
Double Immunofluorescence ◽  
Immunofluorescence Studies

scholarly journals POS0110 ASSOCIATION OF miR-155 AND miR-34a EXPRESSION IN LUPUS NEPHRITIS RENAL TISSUE WITH DISEASE ONSET AND OUTCOMES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 266.1-266
Author(s):  
C. Di Mario ◽  
L. Petricca ◽  
M. R. Gigante ◽  
S. Costanzi ◽  
G. Vischini ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Disease Activity ◽  
Iga Nephropathy ◽  
Lupus Erythematosus ◽  
Clinical Laboratory ◽  
Demographic Data ◽  
Renal Involvement ◽  
Disease Onset ◽  
Control Group ◽  
Complement Components

Background:Epigenetic factors such as non-coding RNA (miRNA) have been shown to be deregulated in Systemic Lupus Erythematosus (SLE). In mouse models, different miRNAs have been associated with lupus nephritis (LN), one of the most severe manifestations of the disease1.Objectives:To evaluate the expression of miR-155 and miR-34a in renal tissues as biomarkers of organ involvement and inflammatory tissue activity in patients with LN.Methods:Thirty-two SLE patients with LN (age: 32.2 ± 9.2 years) with active renal involvement undergoing ultrasound-guided renal biopsy were enrolled between 2010 and 2019. The nephritic manifestation was present in 13 (41%) patients at disease onset (early-LN SLE), while 19 (59%) patients showed a renal involvement after disease onset (long-LN SLE, mean disease duration at LN onset: 7.3 ± 5.7 years). Twelve age-matched patients with IgA nephropathy were enrolled as control group. Clinical, laboratory and demographic data were collected for each patient. Disease activity was recorded using SLEDAI-2K and renal activity, using the total SLEDAI-2K fraction including the items related to the renal involvement. MiR-155 and miR-34a expression in renal tissues was carried out by extraction of total RNA from paraffin-preserved biopsies and was evaluated, after a retrotrascription protocol, using real-time PCR by relative quantification considering the ΔCt (Ct miRNA- Ct housekeeping gene)2.Results:MiR-155 and miR-34a expression in renal tissues was higher in LN-SLE patients as compared to IgA nephropathy patients (ΔCt miR-155: 9.4 ± 10.1 vs 21.9 ± 3.6, p<0.01; ΔCt miR-34a: 10.1 ± 9.8 vs 19.2 ± 3.1, p=0.02). MiR-155 and miR-34a expression in LN-SLE patients renal tissues was comparable in the different histological classes. Furthermore, a direct correlation was observed between the expression of miR-155 and miR-34a (r = 0.91, p <0.001). Dividing patients based on nephritic onset, SLE patients with long-LN showed higher expression of miR-155 (ΔCt 6.1 ± 8.7) and miR-34a (ΔCt 7.1 ± 9.0) as compared to patients with early-LN (miR-155: ΔCt 13.4 ± 10.6 p = 0.08; miR-34a: ΔCt 15.1 ± 9.5 p = 0.02) or patients with IgA nephropathy (miR-155 p<0.01 and miR-34a p<0.01). Moreover, in early-LN SLE it was observed an inverse correlation between miR-34a expression and C3 and C4 complement components (r=-0.7.2; p=0.05 and r=-0.86; p=0.01, respectively) and a direct correlation between miR-155 and 24h-UP (r=0,67; p=0.03). Considering SLE patients with early-LN, the expression of miR-34a was slightly significant in patients who had relapsed (ΔCt 8.2 ± 11.4 vs ΔCt 18.4 ± 7.9 p = 0.08), although no correlation emerged between the expression of miR-155 and miR-34a at the time of the biopsy and with disease activity indices.Conclusion:MiR-155 and miR-34a may represent tissue biomarkers of inflammatory activation in SLE patients with LN; in particular, the higher expression of these miRNA in long-LN and the correlation between miR-155 expression with p24h-UP in early-LN could indicate a possible role of these biomarkers in renal involvement in patients with SLE with later renal onset. The increased expression of miR-34a could give indications of a disease recurrence suggesting a closer monitoring of patients.References:[1]Leiss H et al. Plosone 2017.[2]Alivernini S et al. Nat Commun 2018.Disclosure of Interests:None declared

scholarly journals Renal cortical complement C3 gene expression in IgA nephropathy.

1997 ◽  
Vol 8 (3) ◽  
pp. 415-425
Author(s):  
V Montinaro ◽  
L Gesualdo ◽  
E Ranieri ◽  
R Monno ◽  
G Grandaliano ◽  
...  
Keyword(s):  
Gene Expression ◽  
In Situ Hybridization ◽  
Iga Nephropathy ◽  
Immunoglobulin A ◽  
Complement C3 ◽  
Tubular Atrophy ◽  
Complement Components ◽  
Tubular Cells ◽  
C3 Gene

Glomerular C3 deposits are commonly found in immunoglobulin A (IgA) nephropathy. Renal gene expression and protein synthesis of complement components have been shown in settings of tissue inflammation. In this study, the pathogenetic involvement of locally produced C3 in IgA nephropathy was analyzed. C3 gene expression was analyzed by reverse transcription, polymerase chain reaction, and in situ hybridization techniques. C3 mRNA was detected in 56% of cases, with a significantly higher percentage in patients with moderate-to-severe lesions than in those with mild lesions (P < 0.01). By in situ hybridization, C3 transcript was predominantly expressed by tubular cells and some interstitial cells. C3 mRNA was also observed on glomerular parietal epithelial cells. Immunoreactive native C3 was detected on cortical tubuli by an anti-C3c immunoalkaline-phosphatase technique. A significant correlation was found between renal C3 transcription and glomerulosclerosis, intracapillary proliferation (both P < 0.005) and markers of interstitial damage, including tubular atrophy (P < 0.05), interstitial infiltration (P < 0.05), and fibrosis (P < 0.005). Proteinuria (P < 0.05), but not serum creatinine, at the time of renal biopsy correlated with C3 mRNA. In conclusion, it was demonstrated that the C3 gene was expressed primarily in proximal tubular cells and occasionally in glomerular crescents, and that its expression correlated with clinical and histologic markers of severity and poor outcome of IgA nephropathy. Thus, a pathogenetic involvement of the local transcription and translation of the C3 gene in IgA nephropathy was suggested.

Localization of cell-surface and basement-membrane heparan-sulfate proteoglycans using the malaria circumsporozoite protein

1994 ◽  
Vol 52 ◽  
pp. 294-295
Author(s):  
U. Frevert ◽  
S. Sinnis ◽  
C. Cerami ◽  
V. Nussenzweig
Keyword(s):  
Heparan Sulfate ◽  
Protein A ◽  
Kidney Tissue ◽  
Plasmodium Species ◽  
Its Region ◽  
Basement Membranes ◽  
Heparan Sulfate Proteoglycans ◽  
Infected Mosquito ◽  
Complement Components ◽  
Region Ii

Malaria sporozoites, which invade hepatocytes within minutes after transmission by an infected mosquito, are covered with the circumsporozoite (CS) protein, which in all Plasmodium species contains the conserved region II-plus. This region is also found as a cell-adhesive motif in a variety of host proteins like thrombospondin, properdin and the terminal complement components.The CS protein with its region II-plus specifically binds to heparan sulfate proteoglycans (HSPG) on the basolateral surface of hepatocytes in the space of Disse (FIG. 1), to certain basolateral cell membranes and basement membranes of the kidney (FIG. 2) as well as to heparin in the granules of connective tissue mast cells. The distribution of the HSPG receptors for the CS protein was examined by incubation of Lowicryl K4M or LR White sections of liver and kidney tissue with the recombinant CS ligand, whose binding sites were detected with a monoclonal anti-CS antibody and protein A gold.

Sign in / Sign up

Export Citation Format

Share Document