Serum IgA-Fibronectin Concentration and IgA Nephropathy Diagnosis in Adults With Glomerulonephritis: A Diagnostic Test Study.
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ABSTRACT:
SUBMITTER: Suhail SM
PROVIDER: S-EPMC8178451 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC7270975 | biostudies-literature
Project description:BackgroundIn contrast to intense investigations of galactose-deficient immunoglobulin A (IgA)1 specific immunoglobulin G (IgG), little is known about the IgG subclasses in IgA nephropathy (IgAN). Low IgG4 levels in IgAN were noticed in our preliminary experiment. We aimed to verify the low IgG4 levels and investigate the related immune mechanism in IgAN.MethodsA total of 112 healthy controls (HC) and 112 newly diagnosed IgAN patients were enrolled in this study. Patients with idiopathic membranous nephropathy (IMN), minimal change disease (MCD), or lupus nephritis (LN) were selected as disease controls (DC) (n=122). Serum IgG4 and IgG levels were detected by enzyme-linked immunosorbent assay (ELISA). The IgG4+ B, T helper 1 (Th1), and Th2 cells were measured by flow cytometry. Receiver operating characteristic curves (ROC) were performed to evaluate the diagnostic value of IgG4.ResultsBoth IgG4 levels and IgG4/IgG in IgAN were lower than HC and DC (all P<0.001). Severe IgAN displayed lower IgG4 levels than mild IgAN (P=0.039). Patients with higher risk of renal progression (>50%) demonstrated lower IgG4 levels than lower-risk (≤15%) patients (P=0.019). The cutoff value of IgG4 in differentiating IgAN from HC and DC was 0.26 mg/mL [sensitivity 98.2%, specificity 82.4%, area under the curve (AUC): 0.941, P<0.0001] and 0.17 mg/mL (sensitivity 90.2%, specificity 85.2%, AUC: 0.937, P<0.0001), respectively. IgG4/IgG displayed similar diagnostic and differential ability. The IgG4+ B/B cells (P<0.0001) and Th2/Th (P=0.042) of IgAN were lower than HC.ConclusionsSerum IgG4 levels were low in IgAN. Lower IgG4 levels indicated more severe disease conditions and higher risk of renal progression. Low serum IgG4 seemed to be a potential diagnostic biomarker for IgAN. Decreased IgG4+ B cells and Th2 cells may contribute to the low IgG4 levels in IgAN.
| S-EPMC8246212 | biostudies-literature
Project description:This study identifies immune transcript signatures that may predict IgAV nephritis in skin biopsies and distinguish IgA-IRGN from IgAN and IgAV in kidney biopsies
2023-08-08 | GSE220100 | GEO
Project description:The mechanisms underlying immunoglobulin A nephropathy (IgAN), the most common chronic form of primary glomerulonephritis, remain poorly understood. Streptococcus mutans, a Gram-positive facultatively anaerobic oral bacterium, is a common cause of dental caries. In previous studies, S. mutans isolates that express Cnm protein on their cell surface were frequently detected in IgAN patients. In the present study, inoculation of Cnm-positive S. mutans in the oral cavities of 2-week-old specific-pathogen free Sprague-Dawley rats fed a high-sucrose diet for 32 weeks produced severe dental caries in all rats. Immunohistochemical analyses of the kidneys using IgA- and complement C3-specific antibodies revealed positive staining in the mesangial region. Scanning electron microscopy revealed a wide distribution of electron dense deposits in the mesangial region and periodic acid-Schiff staining demonstrated prominent proliferation of mesangial cells and mesangial matrix. These results suggest that IgAN-like glomerulonephritis was induced in rats with severe dental caries by Cnm-positive S. mutans.
| S-EPMC7952735 | biostudies-literature
Project description:BackgroundThe serum immunoglobulin A (IgA)/C3 ratio is considered to be an effective predictor of IgA nephropathy (IgAN). This study sought to explore the diagnostic value of the IgA/C3 ratio in IgAN among primary glomerular nephropathy patients in China.MethodsWe recruited 1095 biopsy-diagnosed primary glomerular nephropathy patients, including 757 IgAN patients and 338 non-IgAN patients. Patient demographics, serum immunological indices, and other clinical examinations were measured. IgAN cases were propensity score matched (PSM) to non-IgAN cases on the logit of the propensity score using nearest neighbor matching in a 1:1 fashion, with a caliper of 0.02 with no replacements, according to age, gender, BMI, proteinuria level, and estimated glomerular filtration rate (eGFR).ResultsWe found that in both the full cohort and PSM cohort, the IgA/C3 ratio in the IgAN group was significantly higher than that of the non-IgAN group. The same results were also obtained with stratification by different levels of proteinuria and renal function. In the PSM cohort, there was no difference in IgA/C3 ratio in patients with IgAN between different proteinuria groups and different chronic kidney disease (CKD) groups. The area under the ROC curve (AUROC) of the IgA/C3 ratio in distinguishing IgAN among primary glomerular disease was 0.767 in the full cohort, and 0.734 in the PSM cohort. The highest AUROC of the IgA/C3 ratio was in the ≤1 g/d proteinuria group (0.801 in the full cohort, and 0.803 in the PSM cohort); however, there was no difference between all CKD groups. Meanwhile, the diagnostic accordance rate for the diagnosis of IgAN among all patients with an IgA/C3 ratio > 3.5304 was as high as 92.02% in the full cohort. IgAN was independently correlated with IgA/C3 ratio in the full cohort by multivariate logistic regression analysis.ConclusionsThe present study provides clear evidence that the IgA/C3 ratio is an effective predictor of IgA diagnosis, especially in patients with proteinuria ≤1 g/d. In order to study the effectiveness of this biomarker, and to determine a standardized cut-off value, additional multicenter large-scale studies are needed.
| S-EPMC6492345 | biostudies-literature
Project description:Urinary volatile organic compounds (VOCs) analysis for kidney diseases has attracted a large amount of scientific interest recently, and urinary metabolite analysis has already been applied to many diseases. Urine was collected from 15 mesangial proliferative glomerulonephritis (MsPGN) patients, 21 IgA nephropathy (IgAN) patients and 15 healthy controls. Solid phase microextraction-chromatography- mass spectrometry (SPME-GC-MS) was used to analyse the urinary metabolites. The statistical methods principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLSDA) were performed to process the final data. Five metabolites were significantly greater in the group of MsPGN patients than in the normal control group (P < 0.05) while three metabolites were found at increased levels in the group of IgAN patients compared with the normal controls (P < 0.05). In addition, five metabolites were significantly increased in the group of IgAN patients compared with the MsPGN patients (P < 0.05). These five metabolites may be specific biomarkers for distinguishing between MsPGN and IgAN. The analysis of urinary VOCs appears to have potential clinical applications as a diagnostic tool.
| S-EPMC4595831 | biostudies-other
Project description:BACKGROUND:IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Urinary micro-RNA (miRNA) level is increasingly reported to as non-invasive markers of various kidney diseases. We aim to identify urinary miRNA targets for the diagnosis of IgAN. METHODS:In the development cohort, we performed complete miRNA profiling of urinary sediment in 22 patients with IgAN and 11 healthy controls (CTL). Potential miRNA targets were quantified by a separate validation cohort of 33 IgAN patients and 9 healthy controls. RESULTS:In the development cohort, we identified 39 miRNA targets that have significantly different expression between IgAN and CTL (14 up-regulated, and 25 down-regulated). Among the 8 miRNA targets chosen for validation study, urinary miR-204, miR-431 and miR-555 remained significantly reduced, and urinary miR-150 level was significantly increased in the IgAN as compared to CTL. The area-under-curve of the receiver operating characteristic (ROC) curve for urinary mi-204 level for the diagnosis of IgAN was 0.976, and the diagnostic performance of combining additional miRNA targets was not further improved. At the cut-off 1.70 unit, the sensitivity and specificity of urinary miR-204 was 100 and 55.5%, respectively, for diagnosing IgAN. CONCLUSIONS:Urinary miR-150, miR-204, miR-431 and miR-555 levels are significantly different between IgAN and healthy controls; urinary miR-204 level alone has the best diagnostic accuracy.
| S-EPMC6399975 | biostudies-literature
Project description:Staphylococcus infection-associated glomerulonephritis (SAGN) and primary IgA nephropathy (IgAN) are separate disease entities requiring different treatment approaches. However, overlapping histologic features may cause a diagnostic dilemma. An exploratory proteomic study to identify potential distinguishing biomarkers was performed on formalin fixed paraffin embedded kidney biopsy tissue, using mass spectrometry (HPLC-MS/MS) (n?=?27) and immunohistochemistry (IHC) (n?=?64), on four main diagnostic groups-SAGN, primary IgAN, acute tubular necrosis (ATN) and normal kidney (baseline transplant biopsies). Spectral counts modeled as a negative binomial distribution were used for statistical comparisons and in silico pathway analysis. Analysis of variance techniques were used to compare groups and the ROC curve to evaluate classification algorithms. The glomerular proteomes of SAGN and IgAN showed remarkable similarities, except for significantly higher levels of monocyte/macrophage proteins in SAGN-mainly lysozyme and S100A9. This finding was confirmed by IHC. In contrast, the tubulointerstitial proteomes were markedly different in IgAN and SAGN, with a lower abundance of metabolic pathway proteins and a higher abundance of extracellular matrix proteins in SAGN. The stress protein transglutaminase-2 (TGM2) was also significantly higher in SAGN. IHC of differentially-expressed glomerular and tubulointerstitial proteins can be used to help discriminate between SAGN and IgAN in ambiguous cases.
| S-EPMC7560901 | biostudies-literature
Project description:BackgroundIn humans, measurement of serum thyroid-stimulating hormone (TSH) concentration is commonly used as a first-line discriminatory test of thyroid function. Recent reports indicate that canine TSH (cTSH) assays can be used to measure feline TSH and results can help diagnose or exclude hyperthyroidism.ObjectivesTo investigate the usefulness of cTSH measurements as a diagnostic test for cats with hyperthyroidism.AnimalsNine hundred and seventeen cats with untreated hyperthyroidism, 32 euthyroid cats suspected of having hyperthyroidism, and 131 clinically normal cats.MethodsProspective study. Cats referred to the Animal Endocrine Clinic for suspected hyperthyroidism were evaluated with serum T4, T3, free T4 (fT4), and TSH concentrations. Thyroid scintigraphy was used as the gold standard to confirm or exclude hyperthyroidism.ResultsMedian serum TSH concentration in the hyperthyroid cats (<0.03 ng/mL) was significantly (P < .001) lower than concentrations in clinically normal cats (0.05 ng/mL) or euthyroid cats with suspected thyroid disease (0.06 ng/mL). Only 18 (2.0%) hyperthyroid cats had measurable TSH concentrations (?0.03 ng/mL), whereas 114 (69.9%) of the 163 euthyroid cats had detectable concentrations. Combining serum TSH with T4 or fT4 concentrations lowered the test sensitivity of TSH from 98.0 to 97.0%, but markedly increased overall test specificity (from 69.9 to 98.8%).Conclusions and clinical importanceSerum TSH concentrations are suppressed in 98% of hyperthyroid cats, but concentrations are measurable in a few cats with mild-to-moderate hyperthyroidism. Measurement of serum TSH represents a highly sensitive but poorly specific test for diagnosis of hyperthyroidism and is best measured in combination with T4 and fT4.
| S-EPMC4858046 | biostudies-literature
Project description:IgA nephropathy (IgAN), the most frequent primary glomerulonephritis, affects young patients and is associated with a high risk of progression to end-stage renal disease. Consequently, patients with IgAN constitute an important proportion of candidates for kidney transplantation. Several studies showed a significant risk of IgAN recurrence on kidney graft, but the risks factors for recurrence remain to be accurately evaluated. Indeed, early identification of at risk patients may allow the optimization of treatment and the reduction of recurrence rate on the graft. In the present work, we studied the relationship between post-transplant serum IgA (sIgA) levels and the risk of IgAN recurrence after kidney transplantation. Recipients with IgAN had higher levels of sIgA as compared to patients with other nephropathies (p<0.05). The prevalence of IgAN recurrence was 20.8% during the period of analysis (mean follow-up of 6 ± 3.2 years). Serum IgA levels at M6, M12 and M24 post-transplant were significantly higher in patients with IgAN recurrence as compared to those without (p = 0.009, p = 0.035 and p = 0.029, respectively). Using receiver operating curve (ROC), sIgA at M6 and M12 post-transplant were significantly associated with IgAN recurrence (AUC = 0.771, p = 0.004 and AUC = 0.767, p = 0.016, respectively), while serum creatinine and proteinuria were not. Serum IgA level at month 6 was significantly associated with the occurrence of post-transplant IgA recurrence, whether it was analyzed as a continuous or a categorical variable. After successive adjustment on age, gender and proteinuria, sIgA remained a significant risk factor of post-transplant IgAN recurrence. Finally, survival free of IgAN recurrence was significantly better in patients with sIgA<222 mg/dL at month 6 as compare to IgAN patients with sIgA?222 mg/dL (p = 0.03). Thus, the present work supports a link between post-transplant sIgA levels and IgAN recurrence and suggests that sIgA may be a valuable predictive biomarker of IgAN recurrence in kidney transplant recipients.
| S-EPMC5919069 | biostudies-literature