Serum IgG4 level predicts COVID-19 related mortality.
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ABSTRACT:
SUBMITTER: Della-Torre E
PROVIDER: S-EPMC8461218 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Introduction We aimed to investigate the predictors of relapse in immunoglobulin G4-related disease (IgG4-RD), focusing on the serum IgG4 levels during initial treatment. Methods We retrospectively recruited 57 patients with IgG4-RD who were treated with immunosuppressants and elevated serum IgG4 levels in a tertiary hospital between January 2011 and December 2020. They were followed up for ≥ 6 months after initiation of immunosuppressive therapy. Clinical and laboratory findings including serum IgG4 levels (reference value: 6–121 mg/dL) were compared between relapsed (n = 13) and non-relapsed (n = 44) groups. Multivariate Cox regression analysis was used to assess the predictors for relapse. We performed a Kaplan–Meier analysis with a log-rank test to evaluate the cumulative relapse rate for two years. Results Median serum IgG4 levels at baseline were 321 mg/dL in the relapsed group and 299 mg/dL in the non-relapsed group. Serum IgG4 levels were normalized after six months in five (38.5%) relapsed and 28 (63.6%) non-relapsed patients. In multivariate Cox regression analysis, the normalization of serum IgG4 levels at six months was associated with a lower risk of relapse, with a hazard ratio of 0.232 (p = 0.019). Central nervous system involvement was associated with the relapse, with a hazard ratio of 21.130 (p = 0.015). The cumulative relapse rate for two years was lower in the normal serum IgG4 group at six months than in the elevated serum IgG4 group at six months (p = 0.027). Conclusion Our study suggests that normalization of serum IgG4 levels during immunosuppressive treatment for IgG4-RD independently predicts relapse-free outcomes. Thus, monitoring serum IgG4 levels might be used as a marker of prognosis.
| S-EPMC9997947 | biostudies-literature
Project description:We evaluated the impact of serum uric acid (SUA) on mortality in patients with chronic dialysis. A total of 4132 adult patients on dialysis were enrolled prospectively between August 2008 and September 2014. Among them, we included 1738 patients who maintained dialysis for at least 3 months and had available SUA in the database. We categorized the time averaged-SUA (TA-SUA) into 5 groups: <5.5, 5.5-6.4, 6.5-7.4, 7.5-8.4, and ≥8.5 mg/dL. Cox regression analysis was used to calculate the hazard ratio (HR) of all-cause mortality according to SUA group. The mean TA-SUA level was slightly higher in men than in women. Patients with lower TA-SUA level tended to have lower body mass index (BMI), phosphorus, serum albumin level, higher proportion of diabetes mellitus (DM), and higher proportion of malnourishment on the subjective global assessment (SGA). During a median follow-up of 43.9 months, 206 patients died. Patients with the highest SUA had a similar risk to the middle 3 TA-SUA groups, but the lowest TA-SUA group had a significantly elevated HR for mortality. The lowest TA-SUA group was significantly associated with increased all-cause mortality (adjusted HR, 1.720; 95% confidence interval, 1.007-2.937; P = 0.047) even after adjusting for demographic, comorbid, nutritional covariables, and medication use that could affect SUA levels. This association was prominent in patients with well nourishment on the SGA, a preserved serum albumin level, a higher BMI, and concomitant DM although these parameters had no significant interaction in the TA-SUA-mortality relationship except DM. In conclusion, a lower TA-SUA level <5.5 mg/dL predicted all-cause mortality in patients with chronic dialysis.
| S-EPMC4998435 | biostudies-literature
Project description:BackgroundC-reactive protein (CRP) is an acute phase protein produced by the liver in response to systemic inflammation. CRP is a helpful surrogate biomarker used for following the progression and resolution of infection. We aimed to determine the association of baseline CRP level and the temporal change in CRP over time with cryptococcal meningitis outcome.MethodsWe reviewed 168 prospectively enrolled HIV-infected Ugandans with confirmed first-episode cryptococcal meningitis. Baseline plasma CRP collected within 5 days of meningitis diagnosis was categorized into quartiles. We compared baseline CRP with 18-week survival using time-to-event analysis.ResultsOf 168 participants, the baseline first quartile of serum CRP was <29.0 mg/L, second quartile 29.0-49.5 mg/L, third quartile 49.6-83.6 mg/L, and fourth quartile >83.6 mg/L. Baseline CD4 count, HIV viral load, and cerebrospinal fluid results did not differ by CRP quartile. Participants with CRP >49.5 mg/L more likely presented with Glasgow Coma Scale (GCS) <15 (P?=?.03). The 18-week mortality rate was 55% (46/84) in the highest 2 quartile CRP groups (>49.5 mg/L), 41% (17/42) in the mid-range CRP group (29.0-49.5 mg/L), and 14% (6/42) in the low-CRP group (<29.0 mg/L; P?<?.001). After adjustment for possible confounding factors including GCS?<15, CRP remained significantly associated with mortality (adjusted hazard ratio, 1.084 per 10 mg/L; 95% CI, 1.031-1.139; P?=?.0016).ConclusionsHigher baseline CRP is associated with increased mortality in HIV-infected individuals with first-episode cryptococcal meningitis. CRP could be a surrogate marker for undiagnosed coinfections or may reflect immune dysregulation, leading to worse outcomes in persons with advanced AIDS and concomitant cryptococcal meningitis.
| S-EPMC7727340 | biostudies-literature
Project description:ObjectivesVitamin D deficiency was previously correlated with incidence and severity of coronavirus disease 2019 (COVID-19). We investigated the association between serum 25-hydroxyvitamin D (25(OH)D) level on admission and radiologic stage and outcome of COVID-19 pneumonia.MethodsA retrospective observational trial was done on 186 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals hospitalized from March 1, 2020, to April 7, 2020, with combined chest computed tomography (CT) and 25(OH)D measurement on admission. Multivariate regression analysis was performed to study if vitamin D deficiency (25(OH)D <20 ng/mL) correlates with survival independently of confounding comorbidities.ResultsOf the patients with COVID-19, 59% were vitamin D deficient on admission: 47% of females and 67% of males. In particular, male patients with COVID-19 showed progressively lower 25(OH)D with advancing radiologic stage, with deficiency rates increasing from 55% in stage 1 to 74% in stage 3. Vitamin D deficiency on admission was not confounded by age, ethnicity, chronic lung disease, coronary artery disease/hypertension, or diabetes and was associated with mortality (odds ratio [OR], 3.87; 95% confidence interval [CI], 1.30-11.55), independent of age (OR, 1.09; 95% CI, 1.03-1.14), chronic lung disease (OR, 3.61; 95% CI, 1.18-11.09), and extent of lung damage expressed by chest CT severity score (OR, 1.12; 95% CI, 1.01-1.25).ConclusionsLow 25(OH)D levels on admission are associated with COVID-19 disease stage and mortality.
| S-EPMC7717135 | biostudies-literature
Project description:BackgroundSevere disease of COVID-19 and mortality occur more frequently in male patients than that in female patients may be related to testosterone level. However, the diagnostic value of changes in the level of testosterone in predicting severe disease of male COVID-19 patients has not been determined yet.MethodsSixty-one male COVID-19 patients admitted to the First Affiliated Hospital of Zhejiang University School of Medicine were enrolled. Serum samples at different stages of the patients after admission were collected and testosterone levels were detected to analyze the correlation between testosterone level and disease severity. Transcriptome analysis of PBMC was performed in 34 patients.ResultsTestosterone levels at admission in male non-ICU COVID-19 patients (3.7 nmol/L, IQR: 1.5 ∼ 4.7) were significantly lower than those in male ICU COVID-19 patients (6.7 nmol/L, IQR: 4.2 ∼ 8.7). Testosterone levels in the non-ICU group increased gradually during the progression of the disease, while those in the ICU group remained low. In addition, testosterone level of enrolled patients in the second week after onset was significantly correlated with the severity of pneumonia, and ROC curve showed that testosterone level in the second week after onset was highly effective in predicting the severity of COVID-19. Transcriptome studies have found that testosterone levels of COVID-19 patients were associated with immune response, including T cell activation and regulation of lymphocyte activation. In addition, CD28 and Inositol Polyphosphate-4-Phosphatase Type II B (INPP4B) were found positively correlated with testosterone.ConclusionsSerum testosterone is an independent risk factor for predicting the severity of COVID-19 in male patients, and the level of serum testosterone in the second week after onset is valuable for evaluating the severity of COVID-19. Testosterone level is associated with T cell immune activation. The monitoring of serum testosterone should be highlighted in clinical treatment and the related mechanism should be further studied.
| S-EPMC8585551 | biostudies-literature
Project description:Here we recorded serum proteome profiles of 33 COVID-19 patients admitted to the ICU. We received, for most patients, blood samples just after admission and at two more later timepoints. We focused on serum proteins different in abundance between the group of survivors and non-survivors and observed that a rather small panel of about a dozen proteins were significantly different in abundance between these two groups. The four structurally and functionally related type-3 cystatins AHSG, FETUB, HRG and KNG1 were all more abundant in the survivors. The family of inter-α-trypsin inhibitors, ITIH1, ITIH2, ITIH3 and ITIH4, were all found to be differentially abundant in between survivors and non-survivors, whereby ITIH1 and ITIH2 were more abundant in the survivor group and ITIH3 and ITIH4 more abundant in the non-survivors. ITIH1/ITIH2 and ITIH3/ITIH4 also did show opposite trends in protein abundance during disease progression. This panel of eight proteins, complemented with a few more, may represent a panel for mortality risk assessment and eventually even for treatment, by administration of exogenous proteins possibly aiding survival. Such administration is not unprecedented, as administration of exogenous inter-α-trypsin inhibitors is already used in the treatment of patients with severe sepsis and Kawasaki disease. The mortality risk panel defined here is in excellent agreement with findings in two recent COVID-19 serum proteomics studies on independent cohorts, supporting our findings. This panel may not be unique for COVID-19, as some of the proteins here annotated as mortality risk factors have previously been annotated as mortality markers in aging and in other diseases caused by different pathogens, including bacteria.
2021-07-05 | PXD024707 | Pride
Project description:OBJECTIVES:We examined the utility of circulating total and IgG4+ plasmablasts as biomarkers of diagnosis and disease activity in IgG4-related disease (IgG4-RD). MATERIALS METHODS:We evaluated patients with active, untreated, biopsy-proven IgG4-RD affecting various organs. Flow cytometry was used to measure total plasmablast and IgG4+ plasmablast counts by gating peripheral blood for CD19lowCD38+CD20-CD27+ cells and CD19lowCD38+CD20-CD27+IgG4+ cells. Serum IgG4 concentrations were measured by nephelometry. We compared 37 IgG4-RD patients to 35 controls, including healthy individuals (n=14) and patients with other inflammatory diseases before treatment (n=21). RESULTS:The IgG4-RD patients' mean age was 59, and 68% were male. Fourteen patients (38%) had three or more organs involved. The IgG4-RD patients had substantially elevated total plasmablast counts (median 4698/mL, range 610-79524/mL) compared to both untreated disease controls (median 592/mL, range 19-4294/mL; p?<?0.001) and healthy controls (median 94/mL, range 1-653/mL; p?<?0.001). Thirteen IgG4-RD patients (36%) had normal serum IgG4 concentrations (mean 60?mg/dL, range 5-123?mg/dL, normal <135?mg/dL). However, the median plasmablast count was not significantly lower in that subset with normal serum IgG4 concentrations (3784/mL) compared to those with elevated serum IgG4 (5155/mL) (p?=?0.242). Among the 12 rituximab (RTX)-treated patients, the median plasmablast level during disease flare was 6356/mL (range 1123-41589/mL), declining to 1419/mL (range 386/mL-4150/mL) during remission (p?<?0.01). CONCLUSIONS:Circulating plasmablasts are elevated in active IgG4-RD, even in patients with normal serum IgG4 concentrations. Plasmablast counts are a potentially useful biomarker for diagnosis, assessing response to treatment, and determining the appropriate time for re-treatment.
| S-EPMC4656194 | 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: Not available
| S-EPMC7836878 | biostudies-literature
Project description:BackgroundSerum creatine kinase (sCK) reflects CK activity from striated skeletal muscle. Muscle wasting is a risk factor for mortality in patients with chronic kidney disease (CKD). The aim of this study is to evaluate whether sCK is a predictor of mortality and end-stage renal disease (ESRD) in a CKD population.MethodsWe included 1801 non-dialysis-dependent CKD patients from the NephroTest cohort. We used time-fixed and time-dependent cause-specific Cox models to estimate hazard ratios (HRs) for the risk of death and for the risk of ESRD associated with gender-specific sCK tertiles.ResultsHigher sCK level at baseline was associated with a lower age, a higher body mass index, and a higher level of 24 h urinary creatinine excretion, serum albumin and prealbumin (p<0.001). Men, patients of sub-Saharan ancestry, smokers and statin users also experienced a higher level of sCK. In a time-fixed Cox survival model (median follow-up 6.0 years), the lowest gender-specific sCK tertile was associated with a higher risk of death before and after adjustment for confounders (Crude model: hazard ratio (HR) 1.77 (95% CI: 1.34-2.32) compared to the highest tertile; fully-adjusted model: HR 1.37 (95% CI: 1.02-1.86)). Similar results were obtained with a time-dependent Cox model. The sCK level was not associated with the risk of ESRD.ConclusionA low level of sCK is associated with an increased risk of death in a CKD population. sCK levels might reflect muscle mass and nutritional status.
| S-EPMC4889148 | biostudies-literature