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PeerJ 2024Whether serum uric acid (SUA) at baseline could been identiûed as a risk factor for progression in IgA nephropathy (IgAN) patients remains unclear, therefore, long-...
OBJECTIVE
Whether serum uric acid (SUA) at baseline could been identiûed as a risk factor for progression in IgA nephropathy (IgAN) patients remains unclear, therefore, long- term SUA control levels must be monitored. We aimed to investigate the relevant factors affecting time-averaged SUA (TA-SUA) and to assess the prognostic value of TA-SUA in IgAN.
METHODS
This retrospective study included 152 patients with IgAN. The relationships between TA-SUA and clinicopathological features and renal outcomes (defined as the doubling of the baseline serum creatinine level or end-stage renal disease) were analyzed in groups divided by quartiles of TA-SUA levels, the presence of hyperuricemia, and sex.
RESULTS
Patients with high TA-SUA levels had higher levels of baseline SUA, blood urea nitrogen (BUN), triglycerides, serum C3 and serum C4 and were more likely to be male and have hypertension, proteinuria, poor renal function, and pathological injuries including high grades of tubular atrophy/interstitial fibrosis (T1-T2). These patients had a poorer prognosis compared with patients with low TA-SUA levels. The TA-SUA level was positively correlated with baseline age and BUN, triglycerides, serum C3, and serum C4 levels, and negatively correlated with baseline eGFR. Survival curve analysis indicated that persistent hyperuricemia was associated with significantly poorer renal outcomes than normo-uricemia in both men and women. The TA-SUA level also was an independent predictor of renal outcome in patients with IgAN, with optimal cutoû values of 451.38 µmol/L (area under the curve (AUC) = 0.934) for men and 492.83 µmol/L (AUC = 0.768) for women.
CONCLUSIONS
The TA-SUA level is associated with triglyceride level, complement component levels, renal function, and pathological severity of IgAN, and it may be a prognostic indicator in male and female patients with IgAN.
Topics: Humans; Glomerulonephritis, IGA; Male; Female; Uric Acid; Retrospective Studies; Adult; Prognosis; Hyperuricemia; Middle Aged; Disease Progression; Risk Factors; Kidney Failure, Chronic
PubMed: 38650643
DOI: 10.7717/peerj.17266 -
Frontiers in Immunology 2024In light of the public health burden of the COVID-19 pandemic, boosting the safety and immunogenicity of COVID-19 vaccines is of great concern. Numerous Traditional... (Randomized Controlled Trial)
Randomized Controlled Trial
Boosting the immunogenicity of the CoronaVac SARS-CoV-2 inactivated vaccine with Huoxiang Suling Shuanghua Decoction: a randomized, double-blind, placebo-controlled study.
INTRODUCTION
In light of the public health burden of the COVID-19 pandemic, boosting the safety and immunogenicity of COVID-19 vaccines is of great concern. Numerous Traditional Chinese medicine (TCM) preparations have shown to beneficially modulate immunity. Based on pilot experiments in mice that showed that supplementation with Huoxiang Suling Shuanghua Decoction (HSSD) significantly enhances serum anti-RBD IgG titers after inoculation with recombinant SARS-CoV-2 S-RBD protein, we conducted this randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the potential immunogenicity boosting effect of oral HSSD after a third homologous immunization with Sinovac's CoronaVac SARS-CoV-2 (CVS) inactivated vaccine.
METHODS
A total of 70 participants were randomly assigned (1:1 ratio) to receive a third dose of CVS vaccination and either oral placebo or oral HSSD for 7 days. Safety aspects were assessed by recording local and systemic adverse events, and by blood and urine biochemistry and liver and kidney function tests. Main outcomes evaluated included serum anti-RBD IgG titer, T lymphocyte subsets, serum IgG and IgM levels, complement components (C3 and C4), and serum cytokines (IL-6 and IFN-γ). In addition, metabolomics technology was used to analyze differential metabolite expression after supplementation with HSSD.
RESULTS
Following a third CVS vaccination, significantly increased serum anti-RBD IgG titer, reduced serum IL-6 levels, increased serum IgG, IgM, and C3 and C4 levels, and improved cellular immunity, evidenced by reduce balance deviations in the distribution of lymphocyte subsets, was observed in the HSSD group compared with the placebo group. No serious adverse events were recorded in either group. Serum metabolomics results suggested that the mechanisms by which HSSD boosted the immunogenicity of the CVS vaccine are related to differential regulation of purine metabolism, vitamin B6 metabolism, folate biosynthesis, arginine and proline metabolism, and steroid hormone biosynthesis.
CONCLUSION
Oral HSSD boosts the immunogenicity of the CVS vaccine in young and adult individuals. This trial provides clinical reference for evaluation of TCM immunomodulators to improve the immune response to COVID-19 vaccines.
Topics: Adult; Humans; Animals; Mice; COVID-19 Vaccines; COVID-19; Interleukin-6; Pandemics; SARS-CoV-2; Immunoglobulin G; Immunoglobulin M; Drugs, Chinese Herbal; Vaccines, Inactivated
PubMed: 38633263
DOI: 10.3389/fimmu.2024.1298471 -
ImmunoTargets and Therapy 2024Loss of immunoglobulin G (IgG) is accompanied with proteinuria, especially macroproteinuria. The complement system participates kidney disease resulting in proteinuria....
BACKGROUND AND OBJECTIVES
Loss of immunoglobulin G (IgG) is accompanied with proteinuria, especially macroproteinuria. The complement system participates kidney disease resulting in proteinuria. Whether the ratio of complement and IgG is associated with macroproteinuria remains unknown.
DESIGN SETTING PARTICIPANTS AND MEASUREMENTS
A total of 1013 non-dialysis chronic kidney disease (CKD) patients were recruited according to the electrical case records system with 268 patients who endured kidney biopsy. Patients were grouped via the estimated glomerular filtration rate or the levels of proteinuria determination. Biomarkers in different CKD groups or proteinuria groups were compared by one-way ANOVA or independent samples -test. Pearson or spearman analysis was employed to analyze correlation between clinical indexes. Further, influence factor of macroproteinuria was studied by using binary logistic regression. The ROC curve was performed to explore probable predictive biomarker for macroproteinuria.
RESULTS
No significant difference of complement C3 and C4 among CKD1 to CKD5 stages, while higher level of complement C4 in patients with macroproteinuria. Further, C4 had a positive correlation with proteinuria (=0.255, =0.006). After adjusted for age, IgA, IgM, triglyceride and HDL, a binary logistic regression model showed lnC4/IgG (OR=3.561, 95% CI 2.196-5.773, <0.01), gender (OR=1.737, 95% CI 1.116-2.702, =0.014), age (OR=0.983, 95% CI 0.969-0.997, =0.014), and history of diabetes (OR=0.405, 95% CI 0.235-0.699, <0.01) were independent influence factors of macroproteinuria. The area under the ROC curve was 0.77 (95% CI: 0.75-0.82, <0.001) for C4/IgG. The analysis of ROC curves revealed a best cut-off for complement C4 was 0.024 and yielded a sensitivity of 71% and a specificity of 71%. The area under the ROC curve was 0.841 (95% CI: 0.735-0.946, p < 0.001) for C4/IgG in IgA nephropathy patients. The analysis of ROC curves revealed a best cut-off for complement C4/IgG was 0.026 and yielded a sensitivity of 75% and a specificity of 81.2%. The area under the ROC curve for C4/IgG in CKD1-5 stages were 0.772, 0.811, 0.785, 0.835, 0.674.
CONCLUSION
Complement C4/IgG could be used to predict macroproteinuria.
PubMed: 38628623
DOI: 10.2147/ITT.S451307 -
Frontiers in Immunology 2024The complement external quality assurance (EQA) program was first organized in 2010 by a group of researchers working in diagnostic complement laboratories. Starting in...
INTRODUCTION
The complement external quality assurance (EQA) program was first organized in 2010 by a group of researchers working in diagnostic complement laboratories. Starting in 2016, INSTAND e.V., a German, non-profit interdisciplinary scientific medical society dedicated to providing expert EQA programs for medical laboratories, started organizing the EQAs for complement diagnostic laboratories together with the same group of experienced scientists and doctors who also work as EQA experts. The aim of the current work is to provide descriptive analysis of the past seven years' complement EQA results and evaluate timeline changes in proficiency testing.
METHODS
Each year, in March and October, blinded samples (normal, pathological) were sent to the participating diagnostic laboratories, where complement parameters were evaluated exactly as in daily routine samples. Since no reference method/target values exist for these parameters, and participants used different units for measurement, the reported results were compared to the stable mean (Algorithm A) of the participants using the same method/measurement units. A reported result was qualified as "passed" if it fell into the 30-50% evaluation/target range around the mean of reported results (depending on the given parameter).
RESULTS
While the number of participating laboratories has increased in the past years (from around 120 to 347), the number of complement laboratories providing multiple determinations remained mostly unchanged (around 30 worldwide). C3, C4, C1-inhibitor antigen and activity determinations provided the best proficiency results, with >90% passing quotas in the past years, independent of the applied method. Determination of the functional activity of the three activation pathways was good in general, but results showed large variance, especially with the pathological samples. Complement factor C1q and regulators FH and FI are determined by only a few laboratories, with variable outcomes (in general in the 85-90% pass range). Activation products sC5b-9 and Bb were determined in 30 and 10 laboratories, respectively, with typical passing quotas in the 70-90% range, without a clear tendency over the past years.
CONCLUSION
With these accumulated data from the past seven years, it is now possible to assess sample-, method-, and evaluation related aspects to further improve proficiency testing and protocolize diagnostic complement determinations.
Topics: Humans; Laboratories
PubMed: 38596685
DOI: 10.3389/fimmu.2024.1368399 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Apr 2024To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus (SLE) in a real-world setting, and to analyze the...
OBJECTIVE
To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus (SLE) in a real-world setting, and to analyze the related factors of low disease activity and clinical remission.
METHODS
One thousand patients with SLE were enrolled from 11 teaching hospitals. Demographic, clinical and laboratory data, as well as treatment regimes were collec-ted by self-completed questionnaire. The rates of low disease activity and remission were calculated based on the lupus low disease activity state (LLDAS) and definitions of remission in SLE (DORIS). Charac-teristics of patients with LLDAS and DORIS were analyzed. Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission.
RESULTS
20.7% of patients met the criteria of LLDAS, while 10.4% of patients achieved remission defined by DORIS. Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration, compared with non-remission group. Moreover, the rates of anemia, creatinine elevation, increased erythrocyte sedimentation rate (ESR) and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group. Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission. The results of Logistic regression analysis showed that increased ESR, positive anti-dsDNA antibodies, low level of complement (C3 and C4), proteinuria, low household income were negatively related with LLDAS and DORIS remission. However, hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission.
CONCLUSION
LLDAS and DORIS remission of SLE patients remain to be improved. Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.
Topics: Humans; Hydroxychloroquine; Lupus Erythematosus, Systemic; Immunosuppressive Agents; Severity of Illness Index
PubMed: 38595244
DOI: 10.19723/j.issn.1671-167X.2024.02.011 -
JCI Insight Apr 2024BACKGROUNDDiagnosis of PMM2-CDG, the most common congenital disorder of glycosylation (CDG), relies on measuring carbohydrate-deficient transferrin (CDT) and genetic...
BACKGROUNDDiagnosis of PMM2-CDG, the most common congenital disorder of glycosylation (CDG), relies on measuring carbohydrate-deficient transferrin (CDT) and genetic testing. CDT tests have false negatives and may normalize with age. Site-specific changes in protein N-glycosylation have not been reported in sera in PMM2-CDG.METHODSUsing multistep mass spectrometry-based N-glycoproteomics, we analyzed sera from 72 individuals to discover and validate glycopeptide alterations. We performed comprehensive tandem mass tag-based discovery experiments in well-characterized patients and controls. Next, we developed a method for rapid profiling of additional samples. Finally, targeted mass spectrometry was used for validation in an independent set of samples in a blinded fashion.RESULTSOf the 3,342 N-glycopeptides identified, patients exhibited decrease in complex-type N-glycans and increase in truncated, mannose-rich, and hybrid species. We identified a glycopeptide from complement C4 carrying the glycan Man5GlcNAc2, which was not detected in controls, in 5 patients with normal CDT results, including 1 after liver transplant and 2 with a known genetic variant associated with mild disease, indicating greater sensitivity than CDT. It was detected by targeted analysis in 2 individuals with variants of uncertain significance in PMM2.CONCLUSIONComplement C4-derived Man5GlcNAc2 glycopeptide could be a biomarker for accurate diagnosis and therapeutic monitoring of patients with PMM2-CDG and other CDGs.FUNDINGU54NS115198 (Frontiers in Congenital Disorders of Glycosylation: NINDS; NCATS; Eunice Kennedy Shriver NICHD; Rare Disorders Consortium Disease Network); K08NS118119 (NINDS); Minnesota Partnership for Biotechnology and Medical Genomics; Rocket Fund; R01DK099551 (NIDDK); Mayo Clinic DERIVE Office; Mayo Clinic Center for Biomedical Discovery; IA/CRC/20/1/600002 (Center for Rare Disease Diagnosis, Research and Training; DBT/Wellcome Trust India Alliance).
Topics: Humans; Congenital Disorders of Glycosylation; Complement C4; Glycopeptides; Biomarkers; Polysaccharides; Phosphotransferases (Phosphomutases)
PubMed: 38587076
DOI: 10.1172/jci.insight.172509 -
Frontiers in Nephrology 2024Lupus is a diverse autoimmune disease with autoantibody formation. Lupus nephritis carries a grave prognosis. Complement involvement, namely, C1q deficiency, is linked...
INTRODUCTION
Lupus is a diverse autoimmune disease with autoantibody formation. Lupus nephritis carries a grave prognosis. Complement involvement, namely, C1q deficiency, is linked to activity and renal involvement and could help in their assessment. LN therapies include plasma exchange, immune adsorption, and probably hemodiafiltration with online endogenous reinfusion (HFR), together with traditional immunosuppressive therapies.
AIM
The aim of this study was to evaluate the role of HFR in improving signs and symptoms of systemic lupus erythematosus (SLE) activity and laboratory parameters in cases not responding to traditional immunosuppressive therapy.
SETTINGS AND DESIGN
A controlled clinical study was conducted on 60 patients with lupus from Group A that was subdivided into two groups: cases 1 (47 patients), those who received traditional medical treatment, and cases 2 (13 patients), those who underwent HFR in addition to medical treatment. Group B consisted of two subgroups: control 1, composed of 20 healthy age- and sex-matched volunteers, and control 2, consisting of 10 cases with different glomerular diseases other than lupus.
METHODS AND MATERIALS
Serum C1q was determined before and after the HFR as well as induction by medical treatment. Disease activity was assessed using SLEDAI-2K with a responder index of 50; quality of life was assessed using SLEQOL v2, and HFR was performed for the non-responder group.
RESULTS
C1q was lower in cases. It can efficiently differentiate between SLE patients and healthy controls with a sensitivity of 81.67% and a specificity of 90%. It can also efficiently differentiate between SLE patients and the control 2 group (non-lupus patients with renal glomerular disease) with a sensitivity of 83.33% and a specificity of 100%. C1q was more consumed in proliferative lupus, and correlated with anti-ds DNA, C3, and C4.
CONCLUSIONS
C1q efficiently discriminates lupus patients and correlates with proliferative forms. HFR might ameliorate lupus activity and restore C1q.
PubMed: 38586116
DOI: 10.3389/fneph.2024.1269852 -
Journal of Medicine and Life Dec 2023Coronavirus disease 2019 (COVID-19) is a severe and infectious respiratory condition caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This...
Coronavirus disease 2019 (COVID-19) is a severe and infectious respiratory condition caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This case-control study aimed to evaluate serum levels of various immunological markers in patients with COVID-19 compared to those with bacterial pneumonia and a healthy control group. Serum samples were collected from adult participants across various COVID-19 isolation centers, including Kassala State and Ahmed Gasim Hospital, between April and June 2021. The study included 70 patients diagnosed with COVID-19, 30 with bacterial pneumonia, and 50 healthy controls. Serum levels of C-reactive protein (CRP), complement components C3 and C4, and cytokines IL-8, IL-10, IL-12, TNF-α, and IFN-γ were measured using standard reagent kits. Serum level of CRP was significantly elevated in both bacterial pneumonia and COVID-19 but significantly higher among patients with bacterial pneumonia. C3 and C4 were also increased in both patient groups, with C3 significantly higher in bacterial pneumonia. IL-8, IL-10, IL-12, TNF-α, and IFN-γ were significantly increased in bacterial pneumonia and SARS-Cov-2 compared to healthy controls. However, IFN-γ was significantly increased among patients with COVID-19 than patients with bacterial pneumonia. This study highlights the potential significant impact of COVID-19 on the immunological biomarkers investigated.
Topics: Adult; Humans; COVID-19; Interleukin-10; SARS-CoV-2; Tumor Necrosis Factor-alpha; Case-Control Studies; Interleukin-8; Cytokines; Biomarkers; C-Reactive Protein; Pneumonia, Bacterial; Interleukin-12
PubMed: 38585537
DOI: 10.25122/jml-2023-0273 -
Immunity, Inflammation and Disease Apr 2024The purpose of this study was to examine the proportion of CD161 on CD56 natural killer (NK) cells in peripheral blood of primary Sjögren's syndrome (pSS) and...
OBJECTIVES
The purpose of this study was to examine the proportion of CD161 on CD56 natural killer (NK) cells in peripheral blood of primary Sjögren's syndrome (pSS) and investigate its clinical relevance of pSS.
METHODS
The proportion of CD56 NK cells and CD161 on CD56 NK cells was detected by flow cytometry in 31 pSS patients and 29 healthy controls (HCs). The correlations between the proportion of CD161CD56 NK cells and clinical features and disease activity of pSS were further analyzed. Meanwhile, we drew the receiver operating characteristic curve to evaluate the diagnostic value of CD161CD56 NK cells in pSS. In addition, we evaluated the differences in the effects of CD161 cells and CD161 cells in peripheral blood on the function of CD56 NK cells in 5 pSS patients.
RESULTS
The proportion of CD56 NK cells and CD161CD56 NK cells decreased markedly in pSS patients compared to HCs. The correlation analysis showed that the proportion of CD161CD56 NK cells negatively correlated with white blood cells, Immunoglobulin A (IgA), IgM, IgG, European League Against Rheumatism Sjogren's Syndrome Patient Reported Index and European League Against Rheumatism Sjogren's Syndrome Disease Activity Index, and positively correlated with complement C4. The proportion of CD161CD56 NK cells in pSS patients with decayed tooth, fatigue, arthralgia, skin involvement, primary biliary cirrhosis, interstitial lung disease, anti-SSA/Ro60 positive, anti-SSB positive and high IgG was lower than that in negative patients. Furthermore, compared with inactive patients, the proportion of CD161CD56 NK cells decreased obviously in active patients. The area under the curve was 0.7375 (p = .0016), the results indicated that CD161CD56 NK cells had certain diagnostic values for pSS. In addition, the proportion of CD86, HLA-DR, Ki67, FasL, TNF-α, and IFN-γ on CD161CD56 NK cells was lower than that on CD161CD56 NK cells in the peripheral blood of pSS patients.
CONCLUSION
This study suggested that the proportion of CD56 NK cells and CD161CD56 NK cells decreased significantly in pSS patients, and the proportion of CD161CD56 NK cells negatively associated with the clinical features and disease activity of pSS patients. CD161 expression inhibited the function of CD56 NK cells in peripheral blood of pSS patients. The CD161CD56 NK cells may present as a potential target for therapy and a biomarker of disease activity in pSS.
Topics: Humans; Biomarkers; HLA-DR Antigens; Immunoglobulin G; Killer Cells, Natural; Sjogren's Syndrome
PubMed: 38577997
DOI: 10.1002/iid3.1244 -
Lupus Science & Medicine Apr 2024To investigate the real-world impact of intravenous belimumab treatment among patients with SLE using rheumatoid arthritis-derived disease activity measures and...
Evaluating the real-world effectiveness of belimumab in patients with SLE using SLE-related laboratory values and rheumatoid arthritis-derived disease activity measures: RAPID3, swollen joint count and tender joint count.
OBJECTIVE
To investigate the real-world impact of intravenous belimumab treatment among patients with SLE using rheumatoid arthritis-derived disease activity measures and SLE-related laboratory values.
METHODS
This retrospective cohort study used US electronic medical record data from the United Rheumatology Normalised Integrated Community Evidence (UR-NICE) database. Adult patients with SLE who initiated intravenous belimumab between 1 January 2012 and 3 December 2019 (index), had 12 months of pre-index and 24 months of post-index clinical activity, and had ≥6 infusions of belimumab during the 24 months post-index were included. The primary outcome measure was time to first improvement of minimally important difference (MID) for Routine Assessment of Patient Index Data 3 (RAPID3), Patient Pain Index (PPI), swollen joint count, tender joint count (TJC), complement C3 and C4 and anti-double-stranded DNA antibodies during the on-treatment follow-up period of up to 24 months. The secondary outcome measure evaluated the trajectories of these outcome measures for up to 24 months of belimumab treatment.
RESULTS
Of 495 patients included, between 21.0% and 52.1% had ≥1 record for each of the disease activity measures or laboratory values in the pre-index and post-index periods and were included in analyses for that measure. The proportion of patients achieving MID for each measure increased rapidly within 3 months, with continued gradual improvement throughout the remaining on-treatment period, up to 24 months. After 6 months, 52.3% and 55.3% of patients had achieved MID in RAPID3 and PPI, respectively. Outcome measure trajectories indicated improved disease activity with belimumab treatment, particularly in RAPID3, TJC and laboratory values.
CONCLUSIONS
In this real-world effectiveness study, belimumab therapy for SLE resulted in clinically meaningful improvements in rheumatoid arthritis-derived disease activity measures within 3 months of treatment, with patients who remained on belimumab therapy experiencing improvement even up to 24 months of observation.
Topics: Adult; Humans; Retrospective Studies; Treatment Outcome; Lupus Erythematosus, Systemic; Arthritis, Rheumatoid; Antibodies, Monoclonal, Humanized
PubMed: 38575172
DOI: 10.1136/lupus-2023-001111