Perforin gene expression in T lymphocytes correlates with disease activity in immunoglobulin A nephropathy

1992 ◽  
Vol 82 (4) ◽  
pp. 461-468 ◽  
Author(s):  
Tsukasa Nakamura ◽  
Isao Ebihara ◽  
Shiori Osada ◽  
Ko Okumura ◽  
Yasuhiko Tomino ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Lymphocytes ◽  
Disease Activity ◽  
Mrna Expression ◽  
Iga Nephropathy ◽  
Matched Control ◽  
Immunoglobulin A ◽  
Renal Tissue ◽  
Control Subjects ◽  
Protein Excretion

1. We studied perforin gene expression in T lymphocytes obtained from 26 patients with IgA nephropathy and from 15 healthy age-matched control subjects. 2. The majority of patients with IgA nephropathy (96%) had elevated perforin mRNA expression, whereas no perforin mRNA expression was detected in the T lymphocytes of normal control subjects. 3. A positive correlation was noted between perforin mRNA expression and urinary protein excretion. 4. Perforin mRNA expression correlated also with the histopathology in the renal tissue of patients with IgA nephropathy. 5. Sixty per cent of patients with grade III or IV histopathology had high perforin mRNA expression in T lymphocytes [more than (++)]. 6. These studies suggest that disregulation of perforin gene expression in T lymphocytes may be associated with the progression of IgA nephropathy and could be used as an indicator of disease activity.

scholarly journals Renal Endothelin-1 and Endothelin Receptor Type B Expression in Glomerular Diseases with Proteinuria

2001 ◽  
Vol 12 (11) ◽  
pp. 2321-2329
Author(s):  
INGO LEHRKE ◽  
RÜDIGER WALDHERR ◽  
EBERHARD RITZ ◽  
JÜRGEN WAGNER
Keyword(s):  
Gene Expression ◽  
Renal Disease ◽  
Protein Expression ◽  
Mrna Expression ◽  
Iga Nephropathy ◽  
Receptor Type ◽  
Lower Grade ◽  
Glomerular Diseases ◽  
Control Subjects ◽  
Immunohistochemical Analyses

Abstract. The endothelin (ET) system has been studied extensively in experimental models of progressive chronic renal disease, but there is limited information regarding the ET system in renal patients. First, the expression of human ET-1, as well as ET receptor type A (ET-RA) and ET-RB, was studied in 26 renal biopsies from patients with different renal diseases. Gene expression was assessed by quantitative reverse transcription-PCR. Second, ET-1 and ET-RBprotein expression and localization were examined, by immunohistochemical analyses, among a homogeneous cohort of 16 patients with IgA nephropathy and different degrees of proteinuria. ET-RBmRNA expression was threefold higher among patients with higher-grade proteinuria [≥2 g/24 h,n= 10; OD ratio (ODR),i.e., wild-type/mutant mRNA ratio, 1.81 ± 0.3], compared with patients with lower-grade proteinuria (<2 g/24 h,n= 8; ODR, 0.63 ± 0.1;P< 0.01) or control subjects (n= 9; ODR, 0.57 ± 0.1;P< 0.01). ET-1 gene expression was significantly higher among patients with higher-grade proteinuria, compared with patients with lower-grade proteinuria (P< 0.01) or control subjects (P< 0.05). ET-RAmRNA expression was not different among the groups. Patients with higher-grade proteinuria who were receiving angiotensin-converting enzyme inhibitors exhibited significantly (P< 0.05) lower ET-1 and ET-RBmRNA expression, which was comparable to that of control subjects. By using immunohistochemical analyses, an association between proteinuria and expression of ET-1 and ET-RBin proximal tubular epithelial cells and of ET-1 in glomeruli was confirmed in the separate cohort of patients with IgA nephropathy. It is concluded that the increased ET-RBand ET-1 mRNA and protein expression observed in animal models of renal disease is also demonstrable among patients with renal disease and high-grade proteinuria.

Evaluation of Toll-like Receptor 2 Gene Expression in Rheumatoid Arthritis and Correlation with the Disease Activity

2019 ◽  
Vol 13 (2) ◽  
pp. 140-148
Author(s):  
Mai Nasser ◽  
Noha M. Hazem ◽  
Amany Atwa ◽  
Amina Baiomy
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Autoimmune Diseases ◽  
Disease Activity ◽  
Mrna Expression ◽  
Disease Activity Score ◽  
Activity Score ◽  
Tlr2 Expression ◽  
Positive Correlation ◽  
Tlr2 Mrna

Background: Rheumatoid Arthritis (RA) is an autoimmune, chronic, and systematic disease. It affects joints and bones. The exact etiology of RA is still unclear. Varied genetic and environmental factors have been associated with the increased risk for RA. Overactivation of Toll-Like Receptors (TLRs) could initiate the development of autoimmune diseases including RA. Objective: The aim of the study was to evaluate TLR2 gene expression in rheumatoid arthritis patients and investigate its correlation with the disease activity. Materials and Methods: This study included 60 patients and 20 healthy individuals. The patients were diagnosed with RA according to the 2010 American College of Rheumatology/ European League Against Rheumatism criteria (ACR/EULAR). All included subjects did not have any joint disorders and /or autoimmune diseases. RA disease activity was determined by the disease activity score of 28 joints. Whole blood was collected from all participants. Total RNA extraction was done. TLR2 mRNA expression was assessed by reverse transcription-PCR (RT-PCR). Results: TLR2 mRNA expression was found to be significantly higher in RA patients compared to healthy controls. Also, a strong positive correlation was found between TLR2 expression level and the disease activity score. A non significant positive correlation was found between TLR2 expression and serum Rheumatoid Factor (RF) level. Conclusion: TLR2 pathway may have an important role in RA pathogenesis and could be a new biomarker for diagnosis and monitoring disease activity.

scholarly journals Increased TPSAB1 Copy Number in a Family With Elevated Basal Serum Levels of Tryptase

2021 ◽  
Vol 8 ◽  
Author(s):  
Laura Hernández-Hernández ◽  
Catalina Sanz ◽  
Elena Marcos-Vadillo ◽  
Asunción García-Sánchez ◽  
Esther Moreno ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Copy Number ◽  
Family Members ◽  
Copy Number Gain ◽  
Digital Pcr ◽  
Gene Dose ◽  
Control Subjects ◽  
Basal Serum ◽  
The Family

Background: Some recent familial studies have described a pattern of autosomal dominant inheritance for increased basal serum tryptase (BST), but no correlation with mRNA expression and gene dose have been reported.Objective: We analyzed TPSAB1 mRNA expression and gene dose in a four-member family with high BST and in two control subjects.Methods: Blood samples were collected from the family and control subjects. Complete morphologic, immunophenotypical, and molecular bone marrow mast cell (MC) studies were performed. mRNA gene expression and gene dose were performed in a LightCycler 480 instrument. Genotype and CNV were performed by quantitative real-time digital PCR (qdPCR).Results: CNV analysis revealed a hereditary copy number gain genotype (3β2α) present in all the family members studied. The elevated total BST in the family members correlated with a significant increase in tryptase gene expression and dose.Conclusions and Clinical Relevance: We present a family with hereditary α-tryptasemia and elevated BST which correlated with a high expression of tryptase genes and an increased gene dose. The family members presented with atypical MC-mediator release symptoms or were even asymptomatic. Clinicians should be aware that elevated BST does not always mean an MC disorder.

scholarly journals Expression of PDGF and PDGF receptor mRNA in glomeruli in IgA nephropathy.

1997 ◽  
Vol 8 (5) ◽  
pp. 817-819
Author(s):  
Y Terada ◽  
T Yamada ◽  
O Nakashima ◽  
S Sasaki ◽  
H Nonoguchi ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Iga Nephropathy ◽  
Mrna Level ◽  
Immunoglobulin A ◽  
Receptor Expression ◽  
Rt Pcr ◽  
Receptor Mrna ◽  
Beta Receptor ◽  
Urinary Protein Level ◽  
A Chain

This study investigated the mRNA expression of the platelet-derived growth factor (PDGF) A-chain and B-chain and PDGF-beta receptor in glomeruli of 15 immunoglobulin A (IgA) nephropathy kidneys and those with minimal-change lesion (N = 7), membranous nephropathy (N = 3), and focal segmental glomerulonephritis (N = 5), by using competitive RT-PCR methods. The level of PDGF B-chain and beta receptor mRNA expression in IgA nephropathy was significantly higher than in the other forms of glomerulonephritis, but mRNA expressions of PDGF A-chain were not significantly different. Significant correlations were observed between the urinary protein level and the mRNA level of PDGF-beta receptor expression and PDGF B-chain expression, and between the serum creatinine level and the mRNA level of PDGF-beta receptor expression. The PDGF B-chain and beta-receptor may be upregulated and accelerate cell proliferation in a paracrine or autocrine manner and may play a role in the pathogenesis of IgA nephropathy.

scholarly journals Gene expression profiles of circulating leukocytes correlate with renal disease activity in IgA nephropathy

2004 ◽  
Vol 65 (2) ◽  
pp. 420-430 ◽  
Author(s):  
Gloria A. Preston ◽  
Iwao Waga ◽  
David A. Alcorta ◽  
Hitoshi Sasai ◽  
William E. Munger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Disease ◽  
Disease Activity ◽  
Iga Nephropathy ◽  
Expression Profiles ◽  
Gene Expression Profiles

scholarly journals Impaired Insulin-Stimulated Expression of the Glycogen Synthase Gene in Skeletal Muscle of Type 2 Diabetic Patients Is Acquired Rather Than Inherited1

2000 ◽  
Vol 85 (4) ◽  
pp. 1584-1590 ◽  
Author(s):  
Xudong Huang ◽  
Allan Vaag ◽  
Mona Hansson ◽  
Jianping Weng ◽  
Esa Laurila ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Mrna Expression ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Diabetic Patients ◽  
Mrna Levels ◽  
Control Subjects ◽  
Chronic Hyperglycemia

To examine whether defective muscle glycogen synthase (GYS1) expression is associated with impaired glycogen synthesis in type 2 diabetes and whether the defect is inherited or acquired, we measured GYS1 gene expression and enzyme activity in muscle biopsies taken before and after an insulin clamp in 12 monozygotic twin pairs discordant for type 2 diabetes and in 12 matched control subjects. The effect of insulin on GYS1 fractional activity, when expressed as the increment over the basal values, was significantly impaired in diabetic (15.7 ± 3.3%; P &lt; 0.01), but not in nondiabetic (23.7 ± 1.8%; P = NS) twins compared with that in control subjects (28.1 ± 2.3%). Insulin increased GYS1 messenger ribonucleic acid (mRNA) expression in control subjects (from 0.14 ± 0.02 to 1.74 ± 0.10 relative units; P &lt; 0.01) and in nondiabetic (from 0.24 ± 0.05 to 1.81 ± 0.16 relative units; P &lt; 0.01) and diabetic (from 0.20 ± 0.07 to 1.08 ± 0.14 relative units; P &lt; 0.01) twins. The effect of insulin on GYS1 expression was, however, significantly reduced in the diabetic (P &lt; 0.003), but not in the nondiabetic, twins compared with that in control subjects. The postclamp GYS1 mRNA levels correlated strongly with the hemoglobin A1c levels (r = −0.61; P &lt; 0.001). Despite the decrease in postclamp GYS1 mRNA levels, the GYS1 protein levels were not decreased in the diabetic twins compared with those in the control subjects (2.10 ± 0.46 vs. 2.10 ± 0.34 relative units; P = NS). We conclude that 1) insulin stimulates GYS1 mRNA expression; and 2) impaired stimulation of GYS1 gene expression by insulin in patients with type 2 diabetes is acquired and most likely is secondary to chronic hyperglycemia.

scholarly journals Comparison of renal histopathology and gene expression profiles between severe COVID-19 and bacterial sepsis in critically ill patients

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Meint Volbeda ◽  
Daniela Jou-Valencia ◽  
Marius C. van den Heuvel ◽  
Marjolein Knoester ◽  
Peter J. Zwiers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Critically Ill ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Renal Tissue ◽  
Fold Change ◽  
Mrna Levels ◽  
Bacterial Sepsis ◽  
Microvascular Flow

Abstract Background The mechanisms driving acute kidney injury (AKI) in critically ill COVID-19 patients are unclear. We collected kidney biopsies from COVID-19 AKI patients within 30 min after death in order to examine the histopathology and perform mRNA expression analysis of genes associated with renal injury. Methods This study involved histopathology and mRNA analyses of postmortem kidney biopsies collected from patients with COVID-19 (n = 6) and bacterial sepsis (n = 27). Normal control renal tissue was obtained from patients undergoing total nephrectomy (n = 12). The mean length of ICU admission-to-biopsy was 30 days for COVID-19 and 3–4 days for bacterial sepsis patients. Results We did not detect SARS-CoV-2 RNA in kidney biopsies from COVID-19-AKI patients yet lung tissue from the same patients was PCR positive. Extensive acute tubular necrosis (ATN) and peritubular thrombi were distinct histopathology features of COVID-19-AKI compared to bacterial sepsis-AKI. ACE2 mRNA levels in both COVID-19 (fold change 0.42, p = 0.0002) and bacterial sepsis patients (fold change 0.24, p < 0.0001) were low compared to control. The mRNA levels of injury markers NGAL and KIM-1 were unaltered compared to control tissue but increased in sepsis-AKI patients. Markers for inflammation and endothelial activation were unaltered in COVID-19 suggesting a lack of renal inflammation. Renal mRNA levels of endothelial integrity markers CD31, PV-1 and VE-Cadherin did not differ from control individuals yet were increased in bacterial sepsis patients (CD31 fold change 2.3, p = 0.0006, PV-1 fold change 1.5, p = 0.008). Angiopoietin-1 mRNA levels were downregulated in renal tissue from both COVID-19 (fold change 0.27, p < 0.0001) and bacterial sepsis patients (fold change 0.67, p < 0.0001) compared to controls. Moreover, low Tie2 mRNA expression (fold change 0.33, p = 0.037) and a disturbed VEGFR2/VEGFR3 ratio (fold change 0.09, p < 0.0001) suggest decreased microvascular flow in COVID-19. Conclusions In a small cohort of postmortem kidney biopsies from COVID-19 patients, we observed distinct histopathological and gene expression profiles between COVID-19-AKI and bacterial sepsis-AKI. COVID-19 was associated with more severe ATN and microvascular thrombosis coupled with decreased microvascular flow, yet minimal inflammation. Further studies are required to determine whether these observations are a result of true pathophysiological differences or related to the timing of biopsy after disease onset.

scholarly journals Association between a low baseline level of gene expression of energy metabolism in the blood and the development of clinical remission in response to tofacitinib therapy in patients with rheumatoid arthritis

2021 ◽  
Vol 15 (3) ◽  
pp. 20-26
Author(s):  
E. V. Chetina ◽  
A. M. Satybaldyev ◽  
G. A. Markova ◽  
E. Yu. Samarkina ◽  
M. V. Cherkasova
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Disease Activity ◽  
Peripheral Blood ◽  
Clinical Remission ◽  
Energy Generation ◽  
Janus Kinase ◽  
Control Subjects ◽  
Expression Of Genes ◽  
Lower Baseline

Background. Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology, characterized by erosive arthritis (synovitis) and systemic inflammation. Janus kinase (JAK) inhibitors (JAKi) are small molecules that block major signal pathways of many cytokines a growth factors, associated with RA. Identification of patients sensitive to JAKi before treatment could significantly improve therapy outcomes. Currently it is not possible to predict JAKi efficacy in every patient, while some patients are non-responsive to the drug, other develop adverse effects. JAKi effect in RA patients has been recently associated with alterations in mitochondrial function and ATP production. Therefore, we hypothesized that baseline metabolic status of RA patients prior to drug administration can predict the therapeutic outcome.Objective: to investigate the predictive value of baseline expression of genes involved in energy generation in the blood of RA patients, for treatment response to JAKi.Patients and methods. We examined peripheral blood of 28 RA patients aged 52.2±15.6 years, average disease duration 3.5 years (range 0.6–19), treated with Tofacitinib (TOFA, 5–10 mg twice a day) during three months and 26 healthy age-matched control subjects. Clinical response was assessed by disease activity score (DAS28-ESR), immunological status by measurements of serum levels of anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), and C-reactive protein (CRP). Gene expression was assessed in peripheral blood cells by realtime reverse-transcription polymerase chain reaction (RT-PCR). At baseline all patients had Steinbrocker radiographic stage II–III. Most patients (85.7%) were ACPA and RF positive. Thirteen patients had medium, others – high RA activity.Results and discussion. JAKi treatment significantly decreased the inflammatory disease activity according to DAS28. At the end of the study 17 patients demonstrated moderate disease activity (3.2<DAS28<5.1), 4 patients retained high disease activity while 7, attained remission (DAS28 <2.6). Disease remission, achieved on TOFA treatment, was accompanied by significant decrease in CRP and the number of swollen and tender joints. ESR values were not changed significantly. Gene expression analysis revealed that RA patients, which attained clinical remission after TOFA treatment, demonstrated significantly lower baseline expression of genes associated with glycolysis (pyruvate kinase, PKM2) and oxidative phosphorylation (succinate dehydrogenase, SDHB) compared to other examined RA patients, but higher expression of the abovementioned genes compared to control subjects. Moreover, RA patients who attained clinical remission demonstrated a trend to increase of these gene expressions within follow-up period, while in the rest of patients these gene expression was tending to downregulate.Conclusion. Clinical remission in RA patients treated with JAKi is associated with significantly lower baseline expression of genes associated with energy generation pathways (PKM2 and SDHB) compared to other examined subjects.

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.

Prevalence of IgA Nephropathy: A 10 Years’ Experience from Jinnah Postgraduate Medical Centre, Karachi, Pakistan

2020 ◽  
Keyword(s):  
Body Mass Index ◽  
Iga Nephropathy ◽  
Body Mass ◽  
Immunoglobulin A ◽  
Medical Centre ◽  
Male Dominance ◽  
Clinical Indication ◽  
Glomerular Lesion ◽  
Female Ratio ◽  
Nephritic Syndrome

Background: Immunoglobulin A (IgA) is considered the most frequently dealt primary glomerulonephritis, worldwide. The Berger’s disease or IgA nephropathy is a mesangial proliferative glomerulonephritis characterized by deposition of immunoglobulin A in kidneys. The aim of the study was to report the prevalence of IgA nephropathy and the associated parameters (age, gender, and body mass index) in our population. Methods: This was a retrospective study, accomplished at Jinnah Postgraduate Medical Centre, Karachi, Pakistan, from June 2009-May 2019. The histopathology and immunofluorescence of renal biopsies of 519 patients were studied and the prevalence of biopsy proven IgA nephropathy was determined. The Chi-square test was used for association of biopsy proven IgA nephropathy with age, gender, and body mass index. A p-value of 0.05 or less was considered statistically significant. Results: A total of 519 biopsies were studied, out of those, only 4 (0.8%) had IgA nephropathy with male dominance in the last 10 years at Karachi, Pakistan. Male to female ratio was found to be 3:1. The most common clinical indication for renal biopsy was isolated hematuria in 50% of the cases followed by acute kidney injury and nephritic syndrome with 25% each respectively. Most of the patients suffering from proteinuria (> 3.5gm/24 hours), microscopic hematuria in 80% cases, high blood pressure in 50% cases, with other associated symptoms including edema, gastrointestinal, and skin-related symptoms reported. Conclusion: Immunoglobulin A (IgA) nephropathy is not a commonly diagnosed glomerular lesion. Further large-scale cohorts can aid in determining the other factors associated with a low frequency of IgA nephropathy. Keywords: Biopsy; Glomerulonephritis; Immunoglobulin A; Nephropathy.

Sign in / Sign up

Export Citation Format

Share Document