Prognosis of IgA Nephropathy with Stage 3b-5 CKD.

Objective To investigate whether immunosuppressive therapy is beneficial in IgA nephropathy (IgAN) patients with eGFR < 45ml/min/1.73m2. Methods This retrospective study involved 110 IgAN patients for whom clinical data was available; of these, 90 had complete follow-up data. Patients were grouped based on whether they received immunotherapy during follow-up, their renal function, proteinuria levels, and the percentage of crescentic glomeruli observed at the time of renal biopsy. Results The mean eGFR for the participants was 32.0 ± 10.2 ml/min/1.73 m². The average follow-up duration was 46.1 ± 37.9 months. The mean rate of decline in eGFR was 3.6 ml/min/1.73 m² per year. There were 43 (47.8%) composite kidney endpoint occurred in these patients. In the group that received immunotherapy, the incidence of kidney endpoint events was lower than in the untreated group (45.1% vs. 57.9%), but the difference was not statistically significant (P = 0.320). Among patients with stage CKD 3b, the incidence of endpoint events was lower than in those with stages CKD 4 and 5 (36.8% vs. 66.7%, P = 0.006). Conversely, the high proteinuria group saw a higher incidence of endpoint events compared to the low proteinuria group (51.9% vs. 23.1%), although this difference was not statistically significant (P = 0.054). Meanwhile, there was no significant difference in the incidence of endpoint events between the two crescent glomerular ratio groups (48.7% vs. 41.7%, P = 0.649). Kaplan-Meier survival analysis indicated that renal function level (P＜0.001) and proteinuria (P = 0.023) were associated with renal survival in IgAN patients. In contrast, the administration of immunosuppressive therapy (P = 0.288) and the prevalence of C lesions (P = 0.982) did not show a significant association with renal survival. Further, Cox regression analysis identified systolic blood pressure, fibrinogen, and CKD stage as risk factors for eGFR decline in IgAN patients (all P < 0.05). Conclusions IgAN patients with stage 3b-5 CKD exhibited a poor prognosis. It appears that in this specific cohort of IgAN patients, immunosuppressive therapy may not provide significant advantages over supportive care therapeutic regimens in terms of disease management.

Decreased IgA binding levels were accompanied by increased IgG sialylation in IgA nephropathy.

INTRODUCTION: IgA nephropathy (IgAN) is a kidney disorder characterized by the deposition of circulating immune complexes of IgG bound to galactose-deficient IgA1 (Gd-IgA1) in the mesangial glomeruli. However, limited research has been conducted on the levels of IgA binding in relation to the various sialylation profiles of IgG in IgAN. MATERIALS AND METHODS: Sialylated IgG (SA-IgG) and desialylated IgG (DSA-IgG) were isolated from IgAN patients. The IgG-IgA immune complex (IgG-IgA-IC) was detected using two customized commercial ELISA kits. Additionally, IgG was enzymatically digested with neuraminidase to produce DSA-IgG. Subsequently, the binding capacities of both intact IgG and the neuraminidase-digested DSA-IgG with Gd-IgA1 were determined using ELISA kits. RESULTS: Our research revealed that SA-IgG levels were negatively correlated with Gd-IgA1 (R = -0.16, p = 0.03) in IgAN patients. The optical density (OD) levels of IgG-IgA complexes in SA-IgG samples were significantly lower (0.58 ± 0.09) compared to those in DSA-IgG samples (0.78 ± 0.12) when using the Gd-IgA1 assay kit. These results were confirmed using an IgG assay kit, which showed that the SA-IgG groups had significantly lower IgA indices (0.31 ± 0.12) compared to the DSA-IgG groups (0.57 ± 0.19). Furthermore, we investigated the binding capacity of IgG with different sialic acid levels to Gd-IgA1. The results revealed that neuraminidase digestion of IgG increased its propensity to bind to Gd-IgA1. Additionally, we examined the binding capacity of both intact IgG and DSA-IgG to Gd-IgA1 at different mix ratios (IgG 1.5 µg and Gd-IgA1 1.5 µg, IgG 1.5 µg and Gd-IgA1 3 µg, IgG 3 µg and Gd-IgA1 1.5 µg). Interestingly, DSA-IgG demonstrated significantly higher binding capacity to Gd-IgA1 compared to intact IgG at all mix ratios tested. CONCLUSION: The preliminary findings from our present study indicate that the binding level of IgA in purified sialylated IgG is lower than that in desialylated IgG.

Sialylation of IgG inhibits the formation of galactose-deficient IgA1-containing immune complexes and protects mesangial cells from injury in IgA nephropathy.

BACKGROUND: The addition of sialic acid alters IgG from a pro-inflammatory state to an anti-inflammatory state. However, there is a lack of research on the changes of IgG sialylation in IgA nephropathy (IgAN). METHODS: This study included a total of 184 IgAN patients. The sialylated IgG (SA-IgG), IgG-galactose-deficient IgA1 complex (IgG-Gd-IgA1-IC), IL-6, TNF-α, and TGF-ß were detected using commercial ELISA kits. SA-IgG, non-sialylated IgG (NSA-IgG), sialylated IgG-IgA1 complex (SA-IgG-IgA1), and non-sialylated IgG-IgA1 complex (NSA-IgG-IgA1) were purified from IgAN patients and healthy controls (HCs). RESULTS: The mean SA-IgG levels in plasma and B lymphocytes in IgAN patients were significantly higher than those of healthy controls. A positive correlation was found between SA-IgG levels in plasma and B lymphocytes. In vitro, the results showed that the release of IgG-Gd-IgA1-IC was significantly decreased in peripheral blood mononuclear cells (PBMCs) cultured with SA-IgG from both IgAN patients and healthy controls. The proliferation ability and the release of IL-6, TNF-α, and TGF-ß in human mesangial cells (HMCs) were measured after stimulating with SA-IgG-IgA1-IC and NSA-IgG-IgA1-IC. The mesangial cell proliferation levels induced by NSA-IgG-IgA1-IC derived from IgAN patients were significantly higher than those caused by SA-IgG-IgA1-IC derived from IgAN patients and healthy controls. Compared with NSA-IgG-IgA1 from healthy controls, IgAN-NSA-IgG-IgA1 could significantly upregulate the expression of IL-6 and TNF-α in mesangial cells. The data showed that there weren't any significant differences in the levels of IL-6, TNF-α, and TGF-ß when treated with IgAN-SA-IgG-IgA1 and HC-NSA-IgG-IgA1. CONCLUSIONS: The present study demonstrated that the sialylation of IgG increased in patients with IgA nephropathy. It exerted an inhibitory effect on the formation of Gd-IgA1-containing immune complexes in PBMCs and the proliferation and inflammation activation in mesangial cells.

The difference between patients with nephrotic syndrome and nephrotic-range proteinuria in IgA nephropathy: a propensity score matched cohort study.

OBJECTIVE: To date, nephrotic syndrome (NS) has not been well characterized in patients with IgA nephropathy (IgAN). Whether decline in serum albumin is an ominous sign in IgAN patients with massive proteinuria remains unknown. In this study, we evaluated clinical and pathological features of IgAN with NS and compared the differences for these features and long-term outcomes between patients with nephrotic syndrome and nephrotic-range proteinuria. METHODS: A retrospective study was conducted, enrolling 1013 patients with biopsy-proven IgAN. The primary endpoint was the composite of a doubling of the base-line serum creatinine, 50% reduction in eGFR, ESKD (eGFR < 15 ml/min per 1.73 m2) or death. RESULTS: A total of 59 patients were presented with NS (5.8%). The patients with NS showed lower levels of hemoglobin, albumin and higher levels of serum creatinine, serum uric acid and urinary protein than patients without NS. As for pathological parameters, more patients with NS showed a higher prevalence of E1 lesions, T1/2 and C1/2 lesions. Furthermore, we used the propensity score matching method to select 57 patients with nephrotic-range proteinuria and normal serum albumin (NR group) who were comparable to 59 patients with NS. Patients with NS had lower levels of hemoglobin, albumin and IgG and higher levels of TC, LDL, FIB and D-dimer as well as more severe E1 and C1/2 lesions than those in NR group. The S1 lesion was more severe in the NR group than that in the NS group. There was no significant difference in long-term outcome between the two groups. In addition, we found that serum albumin level or the presence of hypoalbuminemia was not a risk factor affecting long-term outcome in patients with massive proteinuria. CONCLUSIONS: A prevalence of 5.8% of NS was presented in IgAN adult patients in our study. IgAN with NS patients had low levels of hemoglobin, albumin, high levels of serum creatinine, serum uric acid, urinary protein and more acute lesions. The prognosis of NS in patients with IgAN was not inferior to that of patients with nephrotic range proteinuria and normal serum albumin.

Ideal physical activity in association with incident ankylosing spondylitis: a community-based, prospective cohort study.

OBJECTIVES: Only limited risk factors for ankylosing spondylitis (AS) have been identified to date. Therefore, we aimed to explore whether cardiovascular health (CVH) behaviours and factors are associated with the risk of developing AS. METHODS: Patients with incident AS were identified in cohorts from two ongoing prospective studies. Assessments were made of the association of AS with individual baseline cardiovascular health lifestyle behaviours (including smoking status, body mass index, physical activity and diet) and cardiovascular health factors (including total cholesterol levels, blood pressure levels and fasting plasma glucose levels), and with a cardiovascular health metric determined by the number of ideal behaviours and factors. Cox regression analysis was used for the estimation of hazard ratios (HRs) for AS. RESULTS: Among 124,303 participants, incident AS was identified in 53 individuals within the 8 years of follow-up. For participants with ideal physical activity (>80 min/week) the HR was 0.21 (95% CI 0.05-0.89) compared with participants without ideal physical activity after adjusting for potential confounders. No signi cant risk of developing AS was associated with baseline smoking, diet, body mass index, blood pressure, fasting blood glucose or total cholesterol status, nor did cardiovascular health metrics. CONCLUSIONS: Adherence to ideal physical activity may reduce the risk of developing AS.

Clinical Significance of Galactose-Deficient IgA1 by KM55 in Patients with IgA Nephropathy.

BACKGROUND: Aberrant galactose-deficient IgA1 molecules (Gd-IgA1) are important causal factors in IgA nephropathy (IgAN); however, the detection of Gd-IgA1 in IgAN is complicated and instable. A monoclonal antibody, KM55, which specifically recognizes Gd-IgA1 has been developed. In the present study, we further explored the clinical significance of Gd-IgA1 using KM55. METHODS: In this study, we enrolled 75 patients with IgAN and 80 healthy controls and detected the plasma Gd-IgA1 levels using the KM55 ELISA method. We also stained -mesangial Gd-IgA1 deposition using KM55. RESULTS: We observed that the levels of plasma Gd-IgA1 in IgAN patients were elevated compared to the corresponding levels of healthy controls. Patients were divided into 2 groups based on the median of Gd-IgA1. Patients with high Gd-IgA1 levels had significantly higher levels of uric acid (UA) and IgA. The other clinical manifestations demonstrated that there were no differences in age, sex, blood pressure, initial proteinuria, hematuria, estimated glomerular filtration rate and Oxford pathological classification between the 2 groups of patients. In addition, positive correlations were observed between Gd-IgA1 and Bb, C3a, C4d and MAC. Mesangial Gd-IgA1 was positive in IgAN but negative in the normal renal tissue adjacent to neoplasm. We next analyzed the correlation between plasma Gd-IgA1 and mesangial Gd-IgA1 deposition. The results showed that a high level of plasma Gd-IgA1 was related to the deposition of mesangial Gd-IgA1, although the difference was not significant. CONCLUSION: We verified the elevated level of plasma and -mesangial Gd-IgA1 in patients with IgAN by KM55, which provided an alternative, easy, and reliable tool for diagnosis and activity assessment of IgAN. The level of plasma Gd-IgA1 positively correlated with levels of UA, total IgA levels, and complement activation products.

Changes E3 ubiquitin protein ligase 1 gene mRNA expression correlated with IgA1 glycosylation in patients with IgA nephropathy.

BACKGROUND: Recent genomewide association study suggested that the top single-nucleotide polymorphism, rs978056, in HECW1 gene (which encodes HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1) associated with the levels of galactose-deficient IgA1 (Gd-IgA1) in IgA nephropathy (IgAN). However, HECW1 expression in IgAN has not yet been examined. METHODS: In the following study, we have enrolled 40 patients with IgAN and 40 healthy controls. The expression level of HECW1, as well as plasma levels of Gd-IgA1 and IgA1, were determined detected. RESULTS: IgAN patients presented with significantly elevated Gd-IgA1 and IgA1 levels compared with those of the healthy controls (p < .001 and p = .03, respectively). We further divided the patients into two groups according to the median level of HECW1 (0.58). We found the levels of Gd-IgA1 and IgA1 were significantly higher in low HECW1 level group compared with those in high HECW1 level group (p = .02 and p = .04, respectively). And HECW1 mRNA expression had a significant inverse correlation with Gd-IgA1 levels in IgAN patients (r= -0.34, p = .03). It seemed that the risk genotype (rs978056 GG) was associated with reduced HECW1 expression in 80 Han Chinese from Beijing, although the difference was not significant (p = .09). No significant association with clinical and pathological manifestations was observed between patients with high and low levels of HECW1. CONCLUSION: We reported for the first time that HECW1 mRNA levels were negatively correlated with Gd-IgA1 levels. Our study points to a new regulatory mechanism of IgAN that can explain the aberrant glycosylation of IgA1.

Clinical and pathological findings of IgA nephropathy following SARS-CoV-2 infection.

The features of IgA nephropathy (IgAN) after SARS-CoV-2 infection have not been well characterized. In this study, we compared the clinical and pathological characteristics of patients with IgAN who had experienced SARS-CoV-2 infection to those who had not. We conducted a retrospective study that enrolled 38 patients with biopsy-proven IgAN following SARS-CoV-2 infection with 4 months (post-SARS-CoV-2 infection group) and 1154 patients with IgAN prior to the pandemic (pre-SARS-CoV-2 infection group). Among the SARS-CoV-2 group cases, 61% were females. The average duration from SARS-CoV-2 infection to renal biopsy was 78.6 days. Prior to SARS-CoV-2 infection, the patients had different presentations of nephropathy. One patient had isolated hematuria, two had isolated proteinuria, twenty presented with both hematuria and proteinuria, and one patient had elevated serum creatinine. Additionally, there were eight cases with uncertain nephropathy history, and six cases did not have a history of nephropathy. Following SARS-CoV-2 infection, five patients experienced gross hematuria, one case exhibited creatinine elevation, and five cases showed an increase in proteinuria. The group of patients infected with SARS-CoV-2 after the COVID-19 pandemic exhibited older age, higher hypertension ratio and lower eGFR values compared to the pre-SARS-CoV-2 infection group. As for pathological parameters, a higher proportion of patients in the post-SARS-CoV-2 infection group exhibited a higher percentage of sclerotic glomeruli and glomerular ischemic sclerosis. There were no significant differences observed between the two groups in terms of therapy involving steroids, immunosuppressants, or RAS inhibitors. IgA nephropathy patients who were infected with SARS-CoV-2 were generally older and experienced more severe kidney damage compared to those without SARS-CoV-2 infection.

Glomerular IgG deposition predicts kidney disease progression in IgA nephropathy.

Objective: We aimed to explore the relationship between the presence and intensity of glomerular IgG deposition and the occurrence of kidney progression events in IgA nephropathy (IgAN). Methods: This retrospective study encompassed a total of 1207 patients with IgAN spanning the period from 2010 to 2022, and complete follow-up data were accessible for 736 patients. The IgG intensity was categorized as follows: low-level, defined as IgG (±) and IgG (+), and high-level, defined as IgG (++) and IgG (+++). Results: We found that the IgG-positive deposited group (N = 113, 9.36%) had significantly higher levels of ESR, TC, LDL, uric acid, proteinuria, and blood glucose, and lower serum albumin level compared to the IgG-negative deposited group (N = 1094, 90.64%). In terms of pathology, the IgG-positive deposited group had a significantly higher percentage of T2 score compared to the IgG-negative deposited group (p = 0.002). At the end of the follow-up period, the IgG-positive deposited group had a higher eGFR decline (-5.7 ± 4.37 ml/year) compared to the IgG-negative deposited group (-4 ± 2.52 ml/year), however, there was not a statistically significant difference between the two groups (p = 0.096). We observed that the high-IgG group had significantly higher level of TG compared to the low-IgG group (p = 0.042). Further analysis revealed that the group of patients with high level of IgG deposition in the kidney experienced a higher incidence of composite kidney outcomes compared to the group with low level of IgG deposition (p = 0.009). Logistic regression analyses showed that high level IgG deposition was an independent risk factor for kidney progression of IgAN (HR 13.419; 95% CI 2.690-66.943, P = 0.029). Further analyses for a solid conclusion using Cox regression that we found high level IgG deposition (HR 115.277; 95% CI 2.299-5.779E3, P = 0.017), eGFR (HR 0.932; 95% CI 0.870-0.999, P = 0.047), and urine protein excretion (HR 1.001; 95% CI 1.000-1.002, P = 0.015) were independent risk factor for kidney progression of IgAN. Conclusions: The intensity of IgG deposition has been found to be associated with the progression of IgAN. Future prospective studies should provide more robust evidence on the impact of IgG deposition on kidney outcomes in patients with IgAN.

Circulating platelets supply ST6Gal-1 in patients with IgA nephropathy.

BACKGROUND: Our previous study showed ST6 ß-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma were associated with a slower progression of IgA nephropathy (IgAN). Platelets are the crucial regulator of cell surface glycosylation events in circulation by supplying glycosyltransferases. METHODS: A total of 180 patients with IgAN were included in this study. ST6Gal-1 levels were analyzed before and after activation of platelets by flow cytometry. RESULTS: We found that IgAN patients in the higher platelet counts group exhibited higher levels of ST6Gal-1 compared with the lower platelet counts group. There was a positive correlation between platelet counts and ST6Gal-1 levels in plasma. Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. No differences were found in terms of the eGFR decline and composite kidney endpoints between two groups. Furthermore, we investigated whether platelets were activated and released ST6Gal-1 in patients with IgAN. The expression of CD62P in platelets in patients with IgAN was higher than those of healthy controls. There were no obvious changes in ST6Gal-1 levels between the rest and the activated platelets within 1 to 2-hour, however, the difference in ST6Gal-1 levels became more pronounced after 4-hour of incubation. CONCLUSIONS: In conclusion, human circulating platelets contain ST6Gal-1, which may be released by the activation of platelets in IgAN.

What is the context? Our previous study showed ST6 ß-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma were associated with a slower progression of IgA nephropathy (IgAN).Platelets are the crucial regulator of cell surface glycosylation events in circulation by supplying glycosyltransferases.Whether elevated ST6Gal-1 in plasma is partly from platelets in IgAN has not been fully elucidated.What is new? A total of 180 patients with IgAN were included in this study.We found that IgAN patients in the higher platelet counts group exhibited higher levels of ST6Gal-1 compared with the lower platelet counts group.Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio.There were no differences in terms of the eGFR decline and composite kidney endpoints between two groups.Furthermore, we explored whether platelets were activated and released ST6Gal-1 in patients with IgAN. The expression of CD62P in platelets in patients with IgAN was higher than that of healthy controls.There were no obvious changes in ST6Gal-1 levels between the rest and the activated platelets within 1 to 2-hour, however, the difference in ST6Gal-1 levels became more pronounced after 4-hour of incubation.What is the impact?Human circulating platelets contain ST6Gal-1, which can be released upon platelets activation. These findings suggest ST6Gal-1 is dynamically controlled by platelet activation to remodel cell surface glycans and alter cell behavior.

Adsorbent-to-photocatalyst: Recycling heavy metal cadmium by natural clay mineral for visible-light-driven photocatalytic antibacterial.

High value-added recycling of hazardous substances emerges as one of the most promising directions in current society, which can simultaneously relieve the environmental burden and obtain useful products. Here, we propose a transformation strategy from adsorbent to photocatalyst by recycling heavy metal with natural clay mineral. Sepiolite is selected as an adsorbent for removing Cd2+ in wastewater due to its excellent adsorption properties in terms of high specific surface area and structural channels. Then, in-situ sulfidation of the adsorbed Cd2+ is carried out, transforming it into CdS/Sep photocatalyst, which exhibits efficient photocatalytic antibacterial activity for Escherichia coli with a sterilization efficiency of 98.8% within 2 h. The intense visible light absorption of CdS and the efficient separation of photogenerated carriers render the prominent antibacterial activity. The main reactive species including superoxide radicals and hydroxyl radicals produced by CdS/Sep under visible light irradiation are diffused into the solution and attack the bacteria surrounding the photocatalysts. This work not only develops new ideas for recycling heavy metals for fabrication of efficient photocatalysts, but also provides a reference for water purification based on cost-effective natural minerals.

Enhanced adsorption and photocatalytic Cr(VI) reduction and sterilization of defective MoS2/PVP.

The exploration of novel nanomaterials to resolve the issues of water pollution with the aid of photocatalytic technology has always been a research hotspot. MoS2 is acknowledged to be one of the promising photocatalysts for its interesting layered structure, suitable band gap, and good chemical stability. However, the fast recombination of photogenerated electrons and holes within the MoS2 impedes its extensive application. Here, hydrophilic polymer (polyvinyl pyrrolidone, PVP) and sulfur vacancy (Vs) are simultaneously introduced into the MoS2 nanosheets to achieve high-efficient photocatalytic hexavalent chromium Cr(VI) removal and antibacterial performance. The incorporation of PVP greatly enhances the adsorption capacity of MoS2, and creating Vs essentially strengthens the photogenerated carrier separation of MoS2. As a result, the Cr(VI) removal efficiency of MoS2-PVP with an appropriate Vs concentration is up to 99.5 % for 3 h. Meanwhile, MoS2-PVP with a relatively higher Vs concentration displays a superior Escherichia coli (E. coli) removal efficiency of 91.8 % within 30 min with the initial E. coli concentration of âˆ¼1.0 × 107 CFU/mL. This study extends photocatalysts to a higher level in designing advanced materials for environmental remediation and establishes a feasible platform for emphasizing the versatility of defect engineering in regulating catalytic activity.

Deciphering prognostic value of CD22 and its contribution to suppression of proinflammatory cytokines production in patients with IgA nephropathy.

BACKGROUND: CD22, mainly expressed in mature B cells, could negatively regulate the function of B cells by binding to sialic acid-positive IgG (SA-IgG). Soluble CD22 (sCD22) is generated by the cleavage of the extracellular domain of CD22 on the membrane surface. However, the role of CD22 in IgA nephropathy (IgAN) remains unknown. METHODS: A total of 170 IgAN patients with a mean follow-up of 18 months were included in this study. The sCD22, TGF-ß, IL-6 and TNF-α were detected using commercial ELISA kits. SA-IgG were purified to stimulate peripheral blood mononuclear cells (PBMCs) from IgAN patients. RESULTS: The plasma levels of sCD22 were lower in IgAN patients in comparison with healthy control. Furthermore, CD22 mRNA levels in PBMCs from patients with IgAN were significantly lower than those of healthy controls. The plasma levels of sCD22 were positively correlated to the mRNA levels of CD22. We found that patients with higher sCD22 levels had a lower level of serum creatinine and a higher level of eGFR on the time of renal biopsy and a higher remission rate of proteinuria and a lower risk of kidney events at the end of follow-up. The logistic regression analysis showed sCD22 was associated with an increased odd of proteinuria remission after being adjusted for eGFR, proteinuria, and SBP. After adjusting for confounding variables, sCD22 was a borderline significant predictor of less kidney composite endpoint. In addition, the sCD22 levels were positively associated with SA-IgG in plasma. The experimental results in vitro showed that addition of SA-IgG enhanced the release of sCD22 in cell supernatant and the phosphorylation of CD22 in PBMCs, further inhibiting the production of IL-6, TNF-α, and TGF-ß in cell supernatant in a dose-dependent manner. Pretreatment with CD22-antibody significantly increased the expression of cytokines in PBMCs. CONCLUSIONS: This is the first study to demonstrate that lower plasma soluble CD22 in IgAN patients and high soluble CD22 levels are associated with an increased odd of proteinuria remission and a decreased odd of kidney endpoint. The interaction between CD22 and SA-IgG can inhibit proliferation and inflammation release in PBMCs from IgAN patients.

Effect of hematuria on the kidney disease progression in IgA nephropathy patients with mild proteinuria and well-preserved renal function.

OBJECTIVE: To investigate whether hematuria is a risk factor in IgA nephropathy (IgAN) patients with mild proteinuria and well-preserved renal function. METHODS: This retrospective study included a total of 63 IgAN patients, with complete clinical data available for 50 patients. Hematuria assessment was conducted using two methods: 1) an automated method using a urine particle analyzer, and 2) a manual method performed by a skilled examiner to examine microscopic urine sediment. RESULTS: The results of hematuria measurement using both automated and manual methods showed a strong linear correlation (r = 0.78, P < 0.001). In IgAN patients, those with high urinary red blood cell count (U-RBCs) exhibited higher serum IgA levels compared to patients with low U-RBCs. Additionally, patients with crescent formation had higher levels of proteinuria compared to those without crescents. Patients who received immunosuppressive treatment displayed higher levels of systolic blood pressure (SBP) and mean arterial pressure (MAP), as well as lower levels of serum hemoglobin and albumin. They also had a higher prevalence of T1 lesions compared to patients who did not undergo immunosuppression. Furthermore, among patients with crescent formation, those who received immunosuppressive agents exhibited higher levels of SBP, diastolic blood pressure (DBP), MAP, and U-RBCs, as well as lower levels of albumin and proteinuria at the time of renal biopsy. No composite kidney endpoint events were observed in these groups of patients. The U-RBCs level was not identified as a risk factor influencing the decline of estimated glomerular filtration rate (eGFR) in IgAN. CONCLUSIONS: The presence of hematuria at the time of biopsy was not found to be associated with kidney disease progression in IgAN patients who had mild proteinuria and well-preserved renal function. This suggests that it is possible that these patients may not derive significant benefits from immunosuppressive therapy.

Mechanistic insights into the link between visfatin gene C-1535T polymorphism and coronary artery disease: an in vitro study.

Visfatin, a pro-inflammatory cytokine predominantly released from leucocytes, is correlated with coronary artery disease (CAD). We have previously reported that the -1535C>T polymorphism (rs1330082), which located on the promoter region of visfatin, was associated with decreased risk of CAD. Here, we investigated the underlying mechanism by which this polymorphism affects the genetic susceptibility to CAD. The difference of the promoter activities between -1535T variant and -1535C allele was tested by luciferase reporter gene assay. The difference of transcription factor binding activities between T and C allele was evaluated by electrophoretic mobility shift assay. In reporter gene assay, we showed that the T variant had a significantly reduced transcriptional activity compared with the C allele. The T-variant significantly attenuated the promoter binding affinity to nuclear transcription factors and this effect became much obvious after treatment with TNF-α. Moreover, competition experiment revealed that the retarded complex formed by T-1535- or C-1535-probe binding to nuclear extracts was nearly completely inhibited by unlabeled activator protein-1 (AP-1) specific probe, indicating that AP-1 might be the target nuclear effector. Taken together, our data provided potential mechanistic link between the visfatin -1535C>T polymorphism and reduced CAD risk.

Elevated activating Fc gamma receptors levels correlated with susceptibility and severity of IgA nephropathy.

Background: It is still uncertain if a dysregulated expression of activating Fc gamma receptors (FcγRs) is associated with the development of immunoglobulin A nephropathy (IgAN). Methods: RNA sequencing was used to determine the mRNA levels of type I FcγRs, which were then verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Commercial ELISA kits were used to detect plasma soluble FcγRIIIb (sFcγRIIIb). Results: We first examined the expression of FcγRs genes in 17 patients with IgAN and six healthy controls. The expression of FcγRIa, FcγRIb, FcγRIIa, FcγRIIc, FcγRIIIa, and FcγRIIIb was shown to be higher in IgAN patients. Even without statistical significance, there was a downward trend in FcγRIIb mRNA levels in IgAN. We observed that the expression levels of activating FcγR mRNAs were consistently higher in an independent set of 20 IgAN patients and 20 healthy controls, confirming the RNA-seq results. FcγRIIIb was the IgG receptor with the greatest difference in expression between the two groups (log2 fold-change = 1.82). We observed a much higher percent of FcγRIIIb positive cells in IgAN by flow cytometry. Next, we measured plasma sFcRIIIb levels in 50 patients with IgAN and 50 healthy controls. The findings revealed that the mean sFcγRIIIb level in plasma in participants with IgAN was much higher than that of healthy controls. Increased sFcγRIIIb levels were associated with a substantial increase in body mass index (BMI), lipid levels, serum creatinine level, and a larger percentage of sclerosis compared with lower sFcRIIIb levels. Patients in the group with higher sFcγRIIIb levels were more likely to get glucocorticoid treatment. Conclusion: The results demonstrated that the mRNA levels of the activating Fc receptor of IgG were significantly increased in IgAN. Patients with higher plasma sFcγRIIIb levels may have had more severe illness than those with lower levels.

Effect of anti-CD19 chimeric antigen receptor T cell therapy in children with relapsed or refractory acute B-lymphocytic leukemia and its prognosis.

PURPOSE: To explore the efficacy of chimeric antigen receptor (CAR)-T cell therapy in children with relapsed or refractory acute B-lymphocytic leukemia (B-ALL) and the influencing factors for their prognosis. METHODS: A retrospective analysis was performed on the clinical data of 46 children with relapsed or refractory B-ALL, who were admitted to and treated in our hospital from January 2015 to October 2017, and the remission and post-infusion adverse reactions were observed in all the patients. Besides, the survival of the patients was followed up and recorded, and the influencing factors for the prognosis were identified by univariate and multivariate Cox regression analyses. RESULTS: Bone marrows were routinely monitored after infusion of CAR-T cells. It was found that 35 children patients achieved morphologic complete remission, had a lower level of minimal residual disease (MRD) than that before treatment and exhibited a response rate of 76.1%, of whom there were 33 cases of MRD-negative remission. Different degrees of cytokine release syndrome (CRS) occurred in 41 out of 46 children, consisting of 37 (80.4%) cases of grade I-II CRS and 4 (8.7%) cases of grade III-IV CRS. The concentrations of serum interleukin (IL)-6, interferon-γ (IFN-γ), ferritin and C-reactive protein (CRP) obviously rose during CRS, and their peak values in the patients with grade III-IV CRS were notably higher than those in grade I-II CRS patients (p<0.001). At the end of follow-up, the median follow-up time was 28.2 months, and the 3-year overall survival (OS) and event-free survival (EFS) rates were 28.3% and 13.0%, respectively. The results also showed that tumor burden ≥5% prior to CAR-T cell therapy [hazard ratio (HR) =3.496, 95% confidence interval (CI) =1.448-9.891, p=0.014] and non-combination with hematopoietic stem cell transplant (HSCT) therapy (HR =0.890, 95% CI =0.543-0.904, p=0.025) were independent risk factors for the prognosis of the patients. CONCLUSIONS: Anti-cluster of classification (CD) 19 CAR-T cell therapy is safe and efficacious against relapsed or refractory B-ALL in children. Reducing the tumor burden before infusion of CAR-T cells and combined with HSCT after infusion are independent factors for improving the prognosis of the patients.

[Association of fibrinogen B beta-chain gene polymorphism with factors affecting obesity].

OBJECTIVE: To study the association of fibrinogen(Fg) B beta -854G/A, -455G/A, -249C/T, -148C/T, 448G/A and Bcl-1G/A gene polymorphisms with factors affecting obesity, and the fibrinogen function such as plasma fibrinogen concentration and molecular reactivity. METHODS: One thousand and three hundred ninety-one subjects from Kailuan corporation were enrolled by medical examination and questionnaire survey, and were divided into normal weight, overweight and obese groups based on body mass index (BMI). Blood biochemistry, fibrinogen concentration, fibrin monomer polymerized velocity (FMPV), and FMPV/A(max) were measured. The gene polymorphisms of the six loci were detected by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequencies of Bcl-1A and its mutated genotype in the overweight group were significantly higher than that in the normal weight group (P< 0.01). In all the three groups, Fg concentration, FMPV, FMPV/A(max) in individuals with B beta -854 mutated genotype were significantly higher than those with wild type genotype (P< 0.01), and in the overweight group, FMPV/A(max) in those with B beta -455 mutated genotype, FMPV in those with B beta -249 mutated genotype, were higher than those with wild type genotype (P< 0.05). CONCLUSION: Individuals with Bcl-1A and its mutated genotype are susceptible to overweight. The B beta -455 and -249 mutated genotypes are accumulative genes for overweight by regulating the Fg function.

Interplay of intestinal microbiota and mucosal immunity in inflammatory bowel disease: a relationship of frenemies.

Inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, are chronic inflammatory disorders of the gastrointestinal tract. With in-depth studies on the mechanisms of the initiation and development of IBD, increasing lines of evidence have focused on the intestinal microbiota in the pathogenesis of IBD. The imbalance between the host and intestinal microbiota induces dysregulated immune response in intestinal mucosa and plays a pivotal role in the initiation of disease and ongoing bowel destruction. This review focuses on recent advances in intestinal microbiota regulation of mucosal immune response as well as novel approaches based on intestinal microbiota alterations in the diagnosis and evaluation of therapeutic response in IBD.

Soluble CD83 suppresses experimental food allergy via regulating aberrant T helper 2 responses.

Aberrant T helper-2 (Th2) responses play a critical role in the pathogenesis of allergic diseases. The underlying mechanism is to be further investigated. It is reported that soluble CD83 (sCD83) has immune-regulatory effects. This study aims to investigate the role of sCD83 in the regulation of Th2 polarization. Blood samples were collected from pediatric patients with food allergy (FA). The Th2 response was analyzed by pertinent immunological approaches. An FA murine model was developed to test the role of sCD83 in the regulation of FA response. We found that the serum sCD83 levels were lower in FA patients. A negative correlation was detected between serum sCD83 levels and serum Th2 cytokine levels. The presence of sCD83 suppressed Th2 cell differentiation and antigen-specific Th2 cell activation. sCD83 upregulated the T-bet expression and suppressed the GATA3 expression in CD4+ T cells. Administration of sCD83 suppressed experimental FA. Pediatric FA patients have low serum sCD83 levels. Administration of sCD83 can alleviate experimental FA via suppression of aberrant Th2 polarization.