Corrigendum: Plasma exosomal IRAK1 can be a potential biomarker for predicting the treatment response to renin-angiotensin system inhibitors in patients with IgA nephropathy.

[This corrects the article DOI: 10.3389/fimmu.2022.978315.].

Plasma exosomal IRAK1 can be a potential biomarker for predicting the treatment response to renin-angiotensin system inhibitors in patients with IgA nephropathy.

Background: Renin-angiotensin system inhibitors (RASi) are the first choice and basic therapy for the treatment of IgA nephropathy (IgAN) with proteinuria. However, approximately 40% of patients have no response to RASi treatment. The aim of this study was to screen potential biomarkers for predicting the treatment response of RASi in patients with IgAN. Methods: We included IgAN patients who were treatment-naive. They received supportive treatment, including a maximum tolerant dose of RASi for 3 months. According to the degree of decrease in proteinuria after 3 months of follow-up, these patients were divided into a sensitive group and a resistant group. The plasma of the two groups of patients was collected, and the exosomes were extracted for high-throughput sequencing. The screening of hub genes was performed using a weighted gene co-expression network (WGCNA) and filtering differentially expressed genes (DEGs). We randomly selected 20 patients in the sensitive group and 20 patients in the resistant group for hub gene validation by real-time quantitative polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was used to evaluate hub genes that predicted the efficacy of the RASi response among the 40 validation patients. Results: After screening 370 IgAN patients according to the inclusion and exclusion criteria and the RASi treatment response evaluation, there were 38 patients in the sensitive group and 32 patients in the resistant group. IRAK1, ABCD1 and PLXNB3 were identified as hub genes by analyzing the high-throughput sequencing of the plasma exosomes of the two groups through WGCNA and DEGs screening. The sequencing data were consistent with the validation data showing that these three hub genes were upregulated in the resistant group compared with the sensitive group. The ROC curve indicated that IRAK1 was a good biomarker to predict the therapeutic response of RASi in patients with IgAN. Conclusions: Plasma exosomal IRAK1 can be a potential biomarker for predicting the treatment response of RASi in patients with IgAN.

Systemic inflammation modulates the ability of serum ferritin to predict all-cause and cardiovascular mortality in peritoneal dialysis patients.

BACKGROUND: This study aimed to ascertain whether the correlation of high serum ferritin with mortality is affected by systemic inflammation and to investigate the optimal serum ferritin level for predicting death when inflammation is considered in peritoneal dialysis (PD) patients. METHODS: We classified 221 patients into four groups according to serum ferritin concentration (100 µg/L) and high-sensitivity CRP (hs-CRP) level (3 mg/L), and followed them regularly from the date of catheterization to Dec 31, 2016, at Sun Yat-Sen Memorial Hospital, China. Clinical and biochemical data were collected at baseline, and clinical outcomes such as all-cause and cardiovascular mortality were assessed. RESULTS: During a median follow-up of 35 months (3 ~ 109 months), 50 (22.6%) deaths occurred. Cardiovascular disease (46.0%) was the most common cause of death, followed by infection (10.0%). The Kaplan-Meier survival analysis and log-rank test revealed significantly worse survival accumulation among PD patients with higher serum ferritin (≥100 µg/L) under elevated hsCRP levels (> 3 mg/L) (P = 0.022). A multivariate Cox regression analysis revealed that an increased serum ferritin level was independently associated with a higher risk of all-cause and cardiovascular mortality in PD patients (HR = 3.114, P = 0.021; and HR = 9.382, P = 0.032) with hsCRP above 3 mg/L after adjusting for relevant confounding factors. CONCLUSION: Higher serum ferritin levels were associated with an increased risk of all-cause and cardiovascular mortality in patients undergoing PD only in the presence of elevated hsCRP levels. The correlation of serum ferritin with poor outcome should take into consideration systemic inflammation.

Peripheral Blood Mononuclear Cell Metabolism Acutely Adapted to Postprandial Transition and Mainly Reflected Metabolic Adipose Tissue Adaptations to a High-Fat Diet in Minipigs.

Although peripheral blood mononuclear cells (PBMCs) are widely used as a valuable tool able to provide biomarkers of health and diseases, little is known about PBMC functional (biochemistry-based) metabolism, particularly following short-term nutritional challenges. In the present study, the metabolic capacity of minipig PBMCs to respond to nutritional challenges was explored at the biochemical and molecular levels. The changes observed in enzyme activities following a control test meal revealed that PBMC metabolism is highly reactive to the arrival of nutrients and hormones in the circulation. The consumption, for the first time, of a high fat⁻high sucrose (HFHS) meal delayed or sharply reduced most of the observed postprandial metabolic features. In a second experiment, minipigs were subjected to two-month HFHS feeding. The time-course follow-up of metabolic changes in PBMCs showed that most of the adaptations to the new diet took place during the first week. By comparing metabolic (biochemical and molecular) PMBC profiles to those of the liver, skeletal muscle, and adipose tissue, we concluded that although PBMCs conserved common features with all of them, their response to the HFHS diet was closely related to that of the adipose tissue. As a whole, our results show that PBMC metabolism, particularly during short-term (postprandial) challenges, could be used to evaluate the whole-body metabolic status of an individual. This could be particularly interesting for early diagnosis of metabolic disease installation, when fasting clinical analyses fail to diagnose the path towards the pathology.

Low level of circulating basophil counts in biopsy-proven active lupus nephritis.

Basophils have been shown to be important players in promoting lupus nephritis (LN). However, the relationship between circulating basophil counts and renal pathology activity of LN remains unclear. In this retrospective study, 159 clinical and pathology samples from patients with biopsy-proven LN were analyzed. The renal activity and classification were evaluated according to renal pathology. The correlations between circulating basophil counts and renal pathology activity index were assessed. Overall, circulating basophil counts correlated with total systemic lupus erythematosus disease activity index (SLEDAI) score (r = - 0.31), renal SLEDAI score (r = - 0.35), activity index (AI) score(r = - 0.40), and renal histologic activity parameters (p < 0.05, respectively). Compared with systemic lupus erythematosus (SLE) non-LN patients, the LN group had lower basophil counts (0.007 ± 0.007 vs. 0.011 ± 0.010 × 109/L, p = 0.04). Subgroup analyses revealed that the circulating basophil counts in group B (AI > 8) were significantly lower than that in group A (AI ≤ 8) (0.004 ± 0.006 vs. 0.009 ± 0.009 × 109/L, p < 0.001). The difference was still significant when eliminating the influence of SLEDAI. Significant differences were found in circulating basophil counts among LN pathology classification groups (p < 0.01). Groups of classes III, IV, and V were more likely to have lower circulating basophil counts when compared with group of class I/II (p < 0.05). These findings suggest a potential role of circulating basophil counts as a convenient and helpful marker for renal activity of LN.

Association of echocardiographic parameters with mortality in hospitalized patients with lupus nephritis.

AIM: Increasing evidence shows that the cardiac involvement attributes to the mortality of patients with lupus nephritis (LN) and echocardiography provides a valid measurement for cardiac disease. However, the association between echocardiographic parameters and mortality in LN patients without cardiac disease history remains unclear. The aim of this study was to explore the relationship between echocardiographic parameters and the mortality in hospitalized LN patients without cardiac disease history. METHODS: A total of 436 LN patients without cardiac disease history who underwent echocardiography at Sun Yat-sen Memorial Hospital, between 1 January 2000 and 31 December 2014, were enrolled into this study. The association between echocardiographic parameters and all-cause and cardiac mortality of LN patients was examined by the Cox proportional hazards model. RESULTS: In this cohort study, the median duration of follow-up was 18 months. Among 436 hospitalized LN patients, 88 patients (20.2%) died. Of them, 38 patients (43.2%) died of cardiac disease. Cardiac symptoms, high systolic blood pressure, high serum levels of C-reactive protein, low serum albumin, low estimated glomerular filtration rate (eGFR), and decreased left ventricular ejection fraction (LVEF) were found to be independently associated with increased all-cause mortality. Furthermore, the cardiac symptoms, low eGFR, increased left ventricular mass index (LVMI), and decreased LVEF were independently correlated with an increased cardiac mortality risk. CONCLUSIONS: Decreased LVEF was associated with increased all-cause and cardiac mortality and increased LVMI was an independent risk factor for cardiac mortality in hospitalized LN patients without cardiac disease history.

Clinical features and mortality in Chinese with lupus nephritis and neuropsychiatric lupus: A 124-patient study.

BACKGROUND: Few investigation has focused on the patients with lupus nephritis (LN) and neuropsychiatric systemic lupus erythematosus (NPSLE). This study was aimed to investigate the clinical features, mortality, and the predictors for mortality of this group of patients. MATERIALS AND METHODS: Medical records were retrospectively reviewed in Sun Yat-sen Memorial Hospital from 1996 to 2012. Data of demographic information, clinical manifestations, laboratory tests, SLE disease activity index 2000 (SLEDAI-2K) score, diagnosis, complications, treatment, and mortality was collected. RESULTS: A total of 124 patients were included in our study. Thirty-five (29.1%) patients had glomerular filtration rate <60 ml/min/1.73 m(2), while 24 (19.4%) experienced acute kidney injury (AKI). Thirteen of the 19 American College of Rheumatology defined NPSLE syndromes were identified. The most frequent manifestation was seizure disorder (56/124, 45.2%), followed by psychosis (37/124, 29.8%) and cerebrovascular disease (35/124, 28.2%). One hundred and five (84.7%) patients had SLEDAI-2K scores ≥15, the mean of which was 21.5 ± 6.2. The mortality during hospitalization was 12.9% (16/124) with NP involvement itself being the leading cause of death (7/16, 43.8%). Multivariate logistic regression confirmed that age <14 years at onset of NPSLE (odds ratios [OR]: 9.95, 95% confidence intervals [CI]: 1.43-69.36, P = 0.020), AKI (OR: 10.40, 95% CI: 2.33-46.48, P = 0.002) and pneumonia (OR: 4.52, 95% CI: 1.14-17.96, P = 0.032) were risk factors for mortality, while cyclophosphamide (CYC) treatment (OR: 0.09, 95% CI: 0.02-0.54, P = 0.008) was a protective factor. CONCLUSION: Most of SLE patients with LN and new-onset NPSLE are in an active disease state. NP manifestation itself was the leading cause of death during hospitalization. Childhood-onset NPSLE, AKI and pneumonia might be predictors of mortality, whereas CYC treatment might improve the prognosis.