Serum C3 Levels Research Articles

The complement system is linked to insulin resistance in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) patients more commonly have insulin resistance (IR) than control subjects. Recent studies have revealed that the complement (C) system is not only a mediator of the immune system but is also related to the pathogenesis of atherosclerosis in the general population. Given that the C alteration is a characteristic of SLE, in the present work we set out to analyse if there is a relationship between the C system and IR in patients with SLE. New generation functional assays of the three pathways of the C system were performed in 225 non-diabetic patients with SLE. In addition, the serum levels of inactive (C1q, C2, C3, C4, factor D), activated (C3a) and regulators (C1 inhibitor and factor H) molecules of the C system were evaluated. Insulin and C-peptide serum levels were measured, and insulin resistance and indices of beta cell function were calculated using the homeostatic model assessment (HOMA). Metabolic syndrome criteria fulfillments were applied. Multivariable linear regression analysis was performed to assess the relationship between C system and IR indices and the presence of metabolic syndrome. After adjusting for covariates that included traditional cardiovascular risk factors associated with IR and prednisone, serum C3a and factor H levels were positively related to higher levels of the HOMA2-IR index. Besides, in the multivariable analysis, after adjustment for covariates, serum levels of C1q and C3 associated with a higher odds ratio for the presence of metabolic syndrome. IR and metabolic syndrome are positively and independently related to higher serum levels of some serum C elements in patients with SLE with a predominant role of the alternative pathway elements.

Biomarkers for Bile Acid Malabsorption in Diarrhea-predominant Irritable Bowel Syndrome: A Systematic Review and Meta-analysis.

A clear relationship of biological indexes between bile acid malabsorption (BAM) and diarrhea-predominant irritable bowel syndrome (IBS-D) has not been well analyzed. This meta-analysis aimed to establish a more convenient method to diagnose BAM in IBS-D patients by comparing the differences in biomarkers between IBS-D patients and healthy people. Multiple databases were searched for relevant case-control studies. Indicators used to diagnose BAM included 75 Se-homocholic acid taurine (SeHCAT), 7α-hydroxy-4-cholesten-3-one(C4), fibroblast growth factor-19 and 48-hour fecal bile acid (48FBA). The rate of BAM (SeHCAT) was calculated by using a random-effect model. The levels of C4, FGF19, and 48FBA were compared, and the overall effect size was combined by a fixed effect model. The search strategy identified 10 relevant studies comprising 1034 IBS-D patients and 232 healthy volunteers. The pooled rate of BAM in IBS-D patients was 32% (according to SeHCAT; 95% CI: 24%-40%). The level of C4 in IBS-D patients was significantly higher than that in the control group (2.86ng/mL; 95% CI: 1.09, 4.63); The level of FGF19 was significantly lower than that in the control group (-33.97pg/mL; 95% CI: -51.13, -16.82); The level of 48FBA was significantly higher than that in the control group (0.059; 95% CI: 0.41, 0.77). The results mainly concluded serum C4 and FGF19 levels in IBS-D patients. Most of the studies have different normal cutoff points of serum C4 and FGF19 levels; the performance of each test should be further estimated. By comparing the levels of these biomarkers, BAM in patients with IBS-D could be identified more accurately, which would lead to more effective treatment.

The Role of C3 and C4 Complement Levels in the Differential Diagnosis of Central Nervous System Demyelinating Diseases (P14-3.016)

<h3>Objective:</h3> Predictive value of C3 and C4 complement levels at the time of the first attack for the definitive diagnosis aimed to be investigated. <h3>Background:</h3> Neuromyelitis Optica Spectrum Disorders (NMOSD) and Multiple Sclerosis (MS) are primary inflammatory demyelinating diseases of the central nervous system. Since they have similar clinical features, difficulties are experienced in the differential diagnosis and, accordingly, in the early decision for the appropriate treatment. It is thought that NMOSD is humoral immunity mediated and MS is T-lymphocyte-mediated. Seronegative and aquaporin-4 positive (AQP4-IgG+) groups are included in NMOSD and it is considered that complement-dependent cytotoxicity has different roles in the pathophysiology of these sub-groups. <h3>Design/Methods:</h3> Peripheral blood samples were obtained from naive patients. 14 Seronegative NMO, 28 AQP4-IgG+ NMO, 23 MOGAD and 15 MS patients were included. Serum C3 and C4 levels were evaluated retrospectively. <h3>Results:</h3> The mean age of the sample was 42±15 and the female ratio was 68.7%. While there was no difference in C3 levels in NMOSD and MS groups, it was determined that C4 levels were lower in NMOSD compared to MS (respectively <i>p</i> values 0.21; 0.035). C4 levels were lower in seronegative and AQP4-IgG+ NMO groups compared to MS (respectively <i>p</i> values 0.026; 0.035). It has been determined that 4.8 cut-off value for C3/C4 ratio can discriminate MS and NMOSD groups with 67% sensitivity and 70% specificity (AUC:0.786; <i>p</i>=0.002). <h3>Conclusions:</h3> While activation of the classical pathway more predominantly decreases the level of C4, alternative pathway decreases the level of C3. The classical pathway in NMOSD was thought to be more affected when compared with MS. Since the involvement of the pathways in the complement system at different levels may be presented with the C3/C4 ratio, it seems likely that this ratio may have value as a candidate marker in the differential diagnosis of neurodemyelinating diseases. <b>Disclosure:</b> Melike Cakan, MD has nothing to disclose. Dr. Cimen has nothing to disclose. Dr. Acar Ozen has nothing to disclose. Dr. Karabudak has nothing to disclose. Meryem Aslı Tuncer has nothing to disclose.

C5a complement levels in clinical remission AQP4-IgG-positive NMO patients.

Neuromyelitis Optica Spectrum Disorders (NMOSD) is an antibody-mediated disorder of the Central Nervous System where a leading role of the complement system has been demonstrated. To measure the levels of complement factors C3, C4 and C5a in serum and plasma of clinical remission patients with AQP4-IgG + NMOSD. Twelve patients with NMOSD AQP4 + according to 2015 criteria from a General Hospital in Buenos Aires, Argentina, were included in the study, and 19 age- and sex-matched healthy volunteers as a control group (HC). AQP4 antibodies were measured in serum by CBA analysis. Fresh blood samples were centrifuged to obtain serum and plasma. C3, C4, and AQP4 antibodies were measured in the serum, whereas C5a was measured in the plasma, which was obtained using Futhan (BD FUT-175®, BD Biosciences, San Jose, CA, USA). The complement factors, C3, C4, and C5a were measured in all samples. The mean concentration of C3 was 130.7mg/dl (SD 16.1mg/dl), and the mean concentration of C4 was 21.6mg/dl (SD 4.8mg/dl); both values were within the normal reference range (C3: 84-193mg/dl; C4: 20-40mg/dl) and were not significantly different (p > 0.05) from the mean levels in healthy controls (C3: 116.9mg/dl; C4: 21.9mg/dl). When analyzing the mean plasma level of C5a, we found a statistically significant difference (p = 0.0444) between the mean concentration of C5a in NMOSD patients (43.1ng/ml; SD 48.7ng/ml) and the HC group (17.7ng/ml; SD 16.7ng/ ml). In conclusion, the present study demonstrates that plasma C5a may be interesting to investigate as a potential biomarker of disease activity in NMOSD, in a larger and prospective cohort.

Serum Interleukin-37 Levels in Patients with Systemic Sclerosis and its Relation with Clinical Findings

Aim: This study investigates serum interleukin(IL)-37 levels in patients with systemic sclerosis (SS) and assesses its relationship with clinical findings.&#x0D; Methods: This study included 35 patients with SS and 30 healthy control subjects. The demographic and clinical characteristics of the patients, such as the presence of Raynaud’s phenomenon, SS subtype, digital ulcers, gastrointestinal and lung involvement, and disease activity, were recorded. The medications used by the patients were recorded, and Serum IL-37 levels were measured using an enzyme-linked immunosorbent assay. The United Kingdom Functional Scoring system was used to evaluate the functional status of the patients, while the Valentini criteria were used to evaluate disease activity. Skin involvement was evaluated based on the modified Rodnan skin score.&#x0D; Results: Although serum IL-37 levels were found to be lower in patients with SS than in the control group, the difference was not statistically significant (p= 0.078). A negative correlation was identified between serum IL-37 levels and C3 levels in patients with SS (p= 0.046). No significant relationship was found between IL-37 levels and other clinical and laboratory parameters.&#x0D; Conclusion: Unlike in patients with autoimmune disorders, serum IL-37 levels were found to be lower in patients with SS than in the control subjects, and IL-37 demonstrated a negative correlation with C3 levels.

Evaluation of the Efficacy of Immune and Inflammatory Markers in the Diagnosis of Lacrimal-Gland Benign Lymphoepithelial Lesion.

This study retrospectively analyzes the immune and inflammatory indices of patients with lacrimal-gland benign lymphoepithelial lesion (LGBLEL) in order to screen out reference indices with higher diagnostic efficacy. The medical histories of patients whose diagnoses of LGBLEL and primary lacrimal prolapse were confirmed by pathology between August 2010 and August 2019 were collected. In the LGBLEL group, the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, rheumatoid factor (RF), and immunoglobulins G, G1, G2, and G4 (IgG, IgG1, IgG2, IgG4) were higher (p < 0.05) and the expression level of C3 was lower (p < 0.05) compared to the lacrimal-gland prolapse group. Multivariate logistic regression analysis showed that IgG4, IgG, and C3 were independent risk factors for predicting LGBLEL occurrence (p < 0.05). The area under the receiver operating characteristic (ROC) curve of the prediction model (IgG4+IgG+C3) was 0.926, which was significantly better than that of any single factor. Therefore, serum levels of IgG4, IgG, and C3 were independent risk factors for predicting the occurrence of LGBLEL, and the combined diagnostic efficacy of IgG4+IgG+C3 was the highest.

T lymphocyte subsets and immunoglobulin and complement levels are associated with the infection status of patients with antineutrophil cytoplasmic antibody-associated vasculitis.

Infection is the leading cause of death in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). The aim of this study was to characterize the immunological features of infectious events occurring in patients with newly diagnosed AAV and to identify possible risk factors associated with infection. The T lymphocyte subsets, immunoglobulin, and complement levels of the groups were compared between infected group and the noninfected group. Further, regression analysis was conducted to determine the association of each variable with the risk of infection. 280 patients with newly diagnosed AAV were enrolled. The average levels of CD3+ T cells (720.0 vs. 920.5, P < 0.001), CD3+CD4+ T cells (392.0 vs. 547.0, P < 0.001), and CD3+CD8+ T cells (248.0 vs. 335.0, P = 0.001), serum IgG (11.66g/L vs. 13.59g/L, P = 0.002), IgA (1.70g/L vs. 2.44g/L, P < 0.001), C3 (1.03g/L vs. 1.09g/L, P = 0.015), and C4 (0.24g/L vs. 0.27g/L, P < 0.001) were significantly lower in the infected group than in the noninfected group. The levels of CD3+CD4+ T cells (adjusted OR 0.997, P = 0.018), IgG (adjusted OR 0.804, P = 0.004), and C4 (adjusted OR 0.001, P = 0.013) were found independently associated with infection. Patients of infected AAV and those without infection differ in T lymphocyte subsets and immunoglobulin and complement levels. Furthermore, CD3+CD4+ T cells counts and serum IgG and C4 levels were independent risk factors with infection in patients with newly diagnosed AAV.

Complement as a Biomarker for Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a disease of immune complex deposition; therefore, complement plays a vital role in the pathogenesis of SLE. In general, complement levels in blood and complement deposition in histological tests are used for the management of SLE. Thus, the evaluation of complement status can be useful in the diagnosis of SLE, assessment of disease activity, and prediction of treatment response and prognosis. In addition, novel complement biomarkers, such as split products and cell-bound complement activation products, are considered to be more sensitive than traditional complement markers, such as serum C3 and C4 levels and total complement activity (CH50), which become more widely used. In this review, we report the complement testing in the management of SLE over the last decade and summarize their utility.

Association between geriatric nutritional risk index and pathological phenotypes of IgA nephropathy.

IgA nephropathy (IgAN) is an immune disease related to oxidative stress and inflammation. It is the most common type of glomerulonephritis in the world and is the cause of chronic kidney disease and end-stage renal disease (ESRD). The Geriatric Nutritional Risk Index (GNRI) is a practical and uncomplicated method to assess the risk of morbidity and mortality, but its ability to assess IgAN is still unclear. Here, we evaluated the association between the GNRI and clinical and histologic findings of IgAN. In a cross-sectional study, we included 348 biopsy-verified IgAN patients. The Oxford classification was used to analyze the pathological characteristics of the included patients. Based on previous studies, the participants were divided into two groups using a cutoff value of 92. Differences in clinicopathological indices between the two groups were compared. The correlation between the GNRI and the indicators was evaluated by using a bivariate correlation analysis. A binary logistic regression analysis was conducted to determine the factors associated with the crescent lesions in IgAN. In this study, 138 out of 348 patients (39.7%) had low GNRI scores (GNRI < 92). Patients in the low GNRI group tended to have a significantly lower body mass index; lower hemoglobin, serum albumin, serum IgG, and serum C3 levels; and higher 24-h proteinuria. The proportions of females, Oxford M1 and Oxford C1/2 were higher in the low GNRI group. The GNRI was positively correlated with body mass index (r = 0.57, P < 0.001), hemoglobin (r = 0.35, P < 0.001), serum albumin (r = 0.83, P < 0.001), serum IgG (r = 0.32, P < 0.001), and serum C3 (r = 0.26, P < 0.001) and negatively correlated with 24-h proteinuria (r = -0.36, P < 0.001) and the proportion of crescents (r = -0.24, P < 0.001). The GNRI scores and serum IgG levels were considered independent factors influencing the crescent lesions in IgAN. The GNRI can reflect the severity of clinical and histologic phenotypes in IgAN patients. Lower GNRI and serum IgG levels may suggest an increased risk of crescent lesions and are potential markers for disease monitoring in IgAN.

Serum and plasma levels of Ba, but not those of soluble C5b-9, might be affected by renal function in chronic kidney disease patients

BackgroundDuring the last few decades, pathogenic mechanisms associated with uncontrolled activation of the complement (C) system and development of anti-C agents have been closely investigated in the field of nephrology. The usefulness of some C products such as C5a and sC5b-9 for diagnostic and prognostic purposes remains controversial. On the other hand, decreased renal function is being observed in many patients with or without nephritis as a background factor in progressively aging societies. We therefore investigated whether renal function influenced the evaluation of various complement components and activation products.MethodsTo investigate the influence of renal function on evaluations of C3, C4, CH50, Ba, C5a and sC5b-9, 40 patients were retrospectively chosen from among 844 patients without active glomerulonephritis from 2009 to 2016. We measured plasma and serum levels of C3, C4, CH50, Ba, C5a and sC5b-9 using enzyme-linked immunosorbent assays and compared the findings with inulin clearance (Cin) as a marker of preserved renal function.ResultsBoth plasma and serum levels of Ba correlated significantly with Cin, but other values did not. Compared with patients with Cin ≥ 60 or ≥ 30 mL/min/1.73 m2, plasma and serum levels of Ba were increased in patients with Cin decreased to < 60 or < 30 mL/min/1.73 m2, but levels of C5a and sC5b-9 were not.ConclusionThe influence of renal function might need to be considered when evaluating Ba, but not C5a and sC5b-9, in plasma and serum samples from chronic kidney disease patients.

The Impact of Lung Cancer in Patients with Combined Pulmonary Fibrosis and Emphysema (CPFE).

Given the high risk of lung cancer (LC) in patients with combined pulmonary fibrosis and emphysema (CPFE), and the difficulty of early diagnosis, it is important to understand the impact of LC in these patients. The effect of LC on the development of acute exacerbation (AE) as a natural course of CPFE is still unknown. We retrospectively reviewed medical records of patients at the West China Hospital and enrolled 59 patients with CPFE combined with LC and 68 CPFE patients without LC for initial diagnosis matched in the same period. We compared the clinical characteristics and imaging features of CPFE patients with LC and without LC, and analyzed the associated factors for the prevalence of LC using binary logistic regression. Cox proportional hazards regression analysis was performed to explore risk factors of AE as a natural course of CPFE. Patients with CPFE combined with LC were more common among elderly male smokers. The most common pathological type of tumor was adenocarcinoma (24/59, 40.7%) and squamous cell carcinoma (18/59, 30.5%). Compared with those in the without LC group, the proportions of men, and ex- or current smokers, and the levels of smoking pack-years, serum CRP, IL-6, fibrinogen, complement C3 and C4 in patients with LC were significantly higher (p < 0.05). There was no significant difference in the proportion of natural-course-related AE (10.2% vs. 16.2%, p > 0.05) between the two groups. Logistic regression analysis demonstrated that pack-years ≥ 20 (OR: 3.672, 95% CI: 1.165-11.579), family history of cancer (OR: 8.353, 95% CI: 2.368-10.417), the level of fibrinogen > 4.81 g/L (OR: 3.628, 95% CI: 1.403-9.385) and serum C3 > 1.00 g/L (OR: 5.299, 95% CI: 1.727-16.263) were independently associated with LC in patients with CPFE. Compared to those without AE, CPFE patients with AE had significantly higher levels of PLR and serum CRP, with obviously lower DLCO and VC. The obviously increased PLR (HR: 3.731, 95% CI: 1.288-10.813), and decreased DLCO%pred (HR: 0.919, 95% CI: 0.863-0.979) and VC%pred (HR: 0.577, 95% CI: 0.137-0.918) rather than the presence of LC independently contributed to the development of natural-course-related AE in patients with CPFE. Pack-years, family history of cancer, the levels of fibrinogen and serum C3 were independently associated with LC in patients with CPFE. The presence of LC did not significantly increase the risk of AE as a natural course of CPFE. Clinicians should give high priority to CPFE patients, especially those with more severe fibrosis and systemic inflammation, in order to be alert for the occurrence of AE.

Comparison of dominant and nondominant C3 deposition in primary glomerulonephritis.

Alternative complement pathway dysregulation plays a key role in glomerulonephritis (GN) and is associated with C3 deposition. Herein, we examined pathological and clinical differences between cases of primary GN with C3-dominant (C3D-GN) and nondominant (C3ND-GN) deposition. We extracted primary GN data from the Korean GlomeruloNEphritis sTudy (KoGNET). C3D-GN was defined as C3 staining two grades greater than C1q, C4, and immunoglobulin via immunofluorescence analysis. To overcome a large difference in the number of patients between the C3D-GN and C3ND-GN groups (31 vs. 9,689), permutation testing was used for analysis. The C3D-GN group exhibited higher serum creatinine (p ≤ 0.001), a greater prevalence of estimated glomerular filtration rate of &lt;60 mL/min/1.72 m2 (p ≤ 0.001), higher (but not significantly so) C-reactive protein level, and lower serum C3 level (p ≤ 0.001). Serum albumin, urine protein/creatinine ratio, number of patients who progressed to end-stage renal disease, and all-cause mortality were comparable between groups. Interstitial fibrosis and mesangial cellularity were greater in the C3D-GN group (p = 0.04 and p = 0.01, respectively) than in the C3ND-GN group. C3 deposition was dominant in the former group (p &lt; 0.001), in parallel with increased subendothelial deposition (p ≤ 0.001). Greater progression of renal injury and higher mortality occurred in patients with C3D-GN than with C3ND-GN, along with pathologic differences in interstitial and mesangial changes.

Associations between serum levels of C3, C4, and total classical complement activity in COVID-19 patients at the time of admission and clinical outcome

In the present study, we investigated the association between complement system status at the time of admission and clinical outcomes in COVID-19 patients. This single-center study was carried out with sixty-one adult patients with COVID-19 who were hospitalized at Imam Hassan Hospital of North Khorasan University of Medical Sciences (Bojnurd, Iran) with less than three days passage since onset of COVID-19 symptoms. Twenty-three healthy volunteers with demographic features similar to the patient group (matched by age and gender) were included in the study as a control group. Patient information including demographic information, demographic data, clinical characteristics, and clinical outcomes were obtained from electronic medical records. Of 61 hospitalized patients with COVID-19, 28 (47.54%) were female, and the average age was 48.78.8 years. The healthy control group included 23 cases (11 (47.8%) female, 12 (52.1%) males, mean age 46.44.4 years). Twenty-one of the 61 patients (34.4%) were admitted to the ICU, and sixteen of them (26.2%) died. Thirty-three (54.10%) patients with COVID-19 were hospitalized for less than 7 days, and 28 (45.90%) of them were hospitalized for 7 days. Our results show that length of hospital stay in the no-ICU group was significantly lower than the ICU admission or death groups (6.490.24 vs. 8.851.59 and 10.531.80, p = 0.0002). The levels of C3, C4, and CH50 were determined through the immunoturbidimetric method and single-radial-haemolysis plates, respectively, on serum samples obtained from patients at the time of admission or those in the control group. Our results indicate that C3, C4 and CH50 levels were markedly lower in COVID-19 patients than in the control group. We also found that complement parameter levels in COVID-19 patients who died or were admitted to ICU were significantly lower than in non-ICU COVID-19 patients. In general, it seems that serum level of C3, C4, and CH50 at admission may predict disease progression or adverse clinical outcome in COVID-19 patients.

Geriatric Pharmacotherapy Case Series: Recurrent Angioedema Following Discontinuation of ACE Inhibitor Therapy.

Introduction Angiotensin-converting enzyme inhibitors (ACEIs) are first-line pharmaceutical agents in common chronic conditions such as hypertension and heart failure with reduced ejection fraction. When angioedema occurs, if secondary to ACEIs, discontinuation of the ACEI is necessary to mitigate the risk of recurrent angioedema. While angioedema is a well-known adverse effect of ACEIs, it is not well-known that angioedema may recur even after ACEI discontinuation. Additionally, only few reports in the literature describe this phenomenon. This case describes an older man with a history of chronic obstructive pulmonary disease, hypothyroidism, diabetes mellitus, hypertension, and heart failure who presented from an assisted living facility with recurrent angioedema 12 days after an initial episode of angioedema where his ACEI therapy (enalapril) was discontinued. Assessment Empiric methylprednisolone, diphenhydramine, intramuscular epinephrine, intravenous C1 esterase inhibitor Berinert®, and two units of fresh frozen plasma was given in the emergency department. The patient was monitored in the intensive care unit because of mild airway compromise but did not require invasive airway protection. Serum C4 level was normal, ruling out hereditary angioedema. Outcome Patient was discharged after five days in stable condition with resolution of symptoms. Conclusion ACEIs are the most common cause of drug-induced angioedema in the United States. Angioedema is self-limiting swelling that requires close airway monitoring. While health professionals recognize the risk for angioedema with active ACEI use, it is not well known that the risk of angioedema may occur for months following cessation of ACEI therapy. Increased awareness of delayed ACEI-induced angioedema following ACEI discontinuation is important for both providers and pharmacists to provide appropriate diagnosis and monitoring. Improved awareness would also allow patients with a history of ACEI-induced angioedema to be cognizant of the potential for recurrence following drug discontinuation.

Related factors of crescents and prognosis in IgA nephropathy.

IgA nephropathy (IgAN) has the highest prevalence among primary glomerular diseases worldwide, and crescent is a risk predictor of renal prognosis in IgAN. However, this is still controversial, and more research is needed to further confirm the importance of crescents in IgAN patients. So we aim to investigate the related factors and prognosis of IgAN with crescents. 178 patients diagnosed with IgAN by renal biopsy were selected into a crescent group (C group, C1: 0% < crescent proportion < 25%, C2: crescent proportion ≥ 25%) and a non-crescent group (C0 group). The clinical and renal pathology indexes were compared, and the progression of proteinuria and renal function were followed up. Compared with the C0 group, the C group revealed lower level of serum albumin, hemoglobin, serum C3, and IgA complements, higher level of 24-hour urine protein quantity and urine erythrocyte count. Statistical differences in the degree of mesangial hyperplasia and C3 complement deposition were found between the two groups. Logistic regression analysis showed that hemoglobin and C3 complement deposition (+ and + +) were independent related factors of crescents in IgAN. Cumulative renal survival rate in C2 was significantly lower than in C1 (χ2 = 5.532, p = 0.019). IgAN patients with more crescents (≥ 25%) (adjusted hazard ratio (AHR) = 4.905, 95% CI: 1.135 - 21.208, p = 0.0033) and platelets (AHR = 1.016, CI: 1.006 - 1.023, p = 0.001) were more likely to progress to the end event in Cox regression analysis. IgAN patients with crescents may have severe clinical symptoms and poor prognosis. The crescents and serum platelet count are risk predictors of poor prognosis in IgAN.

Circulating platelets supply ST6Gal-1 in patients with IgA nephropathy

ABSTRACT Background Our previous study showed ST6 β-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.

Immune phenotype changes in IgG4-related disease: CD161 + Treg and Foxp3 + Treg.

We aimed to characterize the alterations in the immune phenotypes and explore the potential relevance to pathogenesis in IgG4-RD. Forty-two IgG4-RD patients and thirty-eight healthy controls were recruited in this study. Peripheral immunocompetent cells including T cells, CD4 + T cells, CD8 + T cells, B cells, NK cells CD4 + CD45RA + T cells (naïve T cells), CD4 + CD25 - / + Foxp3 - T cells (Teff), CD4 + CD25hiCD127lowCD161 + T cells (CD161 + Treg), CD4 + CD25hiFoxp3 + T cells (Foxp3 + Treg), CD4 + CD4RA-CXCR5 + PD1 + CCR7low T cells (pTfh), T helper (Th) 1, Th2, and Th17 before and after treatment were immunophenotyped by flow cytometry. Compared with healthy controls, IgG4-RD patients showed higher proportions of NK (20.1% vs 13.6%, p < 0.01), Th1 (CD4 + IFN-γ + : 17.9% vs 14.2%, p = 0.061; TNF-α: 43.7% vs 36.7%, p < 0.05), Th2 (CD4 + IL-4 + : 2.4% vs 1.3%, p < 0.0001), CD161 + Treg (14.9% vs 11.6%, p < 0.01), pTfh (3.2% vs 2.4%, p < 0.05), and Foxp3 + Treg (8.3% vs 7.0%, p < 0.01) and lower proportions of B lymphocytes (8.4% vs 13.1%, p < 0.001), Teff (91.6% vs 92.6%, p < 0.01), and naïve Th cells (19.9% vs 32.1%, p < 0.01) before treatment. Foxp3 + Treg percentage decreased significantly after treatment (8.6% vs 6.9%, p < 0.05). Both serum C3 (r = - 0.6374, p < 0.01) and C4 (r = - 0.6174, p < 0.01) levels were in negative correlation with CD161 + Treg. The eosinophil percentage was positively correlated with Foxp3 + Treg (r = 0.5435, p < 0.05). Serum IgE level was positively correlated with Th2 (r = 0.5545, p < 0.05). There was a positive correlation between CD161 + Treg and pTfh (r = 0.4974, p < 0.05) while a negative correlation between Th2 and B cells (r = - 0.4925, p < 0.05). Immune phenotypes were altered in IgG4-RD. Treg/Teff balance was shifted toward Treg in IgG4-RD. CD161 + Treg was likely to be involved in the pathogenesis of IgG4-RD. Key Points •Immune phenotypes were altered in B cells, T cells, and NK cells in IgG4-RD. •Treg/Teff balance was shifted toward Treg in IgG4-RD. •CD161+ Treg maybe play a proinflammatory role in IgG4-RD.

Low serum complement level is associated with higher mortality in tuberculous meningitis: a retrospective cohort study.

We evaluated the associations between serum complement levels and tuberculous meningitis (TBM), bacterial meningitis (BM), and viral meningitis (VM), as well as the association between serum complement levels and mortality in TBM. Background information and blood/cerebrospinal fluid analysis results were collected from 2009 to 2019. Patients who had serum complement level data collected at admission and who were diagnosed with TBM (n = 97), BM (n = 31), or VM (n = 557) were enrolled. Initial serum complement levels were significantly lower in the TBM group than the VM group in both the total population and the propensity score-matched population. In the TBM and VM groups, compared to patients with initial highest-quartile C4 level, patients in the lowest quartile (C4 < 24.3 mg/dL) had significantly greater odds of TBM diagnosis (odds ratio, 2.2; 95% confidence interval, 1.0-4.5; p = 0.038). In the TBM group, patients with the lowest-quartile C3 level (<96.9 mg/dL) experienced a significantly higher 90-day mortality rate compared to other TBM patients (hazard ratio, 19.0; 95% confidence interval, 2.1-167.4.5; p = 0.008). Both serum C3 and C4 levels were significantly lower in the TBM group than in the VM group. TBM patients with lower serum C3 level had a significantly higher mortality rate than those with higher C3 level.

Obesity Contributes to Inflammation in Patients with IBS via Complement Component 3 and C-Reactive Protein.

Irritable Bowel Syndrome (IBS) is usually a lifelong state that disturbs the digestive system. IBS has been linked to low-grade inflammation and the release of inflammatory mediators into the bloodstream. This could be associated with the degree of obesity presented by patients with IBS. Reports imply that IBS is more frequent in obese patients than in the overall population, with a prevalence of up to 31%. Here, we evaluated the serum levels of immunological and inflammation molecules and their correlation with Body Mass Index in IBS patients and the healthy control (HC). Seventy-nine serum samples of the IBS patients and thirty-five of the HC group were analyzed to determine the levels of each molecule and compare them with their BMI. Serum levels of C3 and C4 were significantly increased in IBS patients. C3 and C4 levels were higher in IBS-M and IBS-D subtypes compared with the HC group. When patients were grouped by BMI, a positive correlation between serum C3 (r = 0.49, p < 0.0001) and CRP (r = 0.40, p < 0.001) levels was found. Our results show, for the first time, a correlation between immunological molecules and BMI in IBS patients, suggesting that the inflammatory nature of obesity could contribute to the development of the symptoms in IBS through the stimulation and release of proteins as complement components and CRP.

Changes in Maternal Serum Levels of C3 and C4 Complement Components in Different Delivery Methods and Postpartum Hemorrhage.

Activation of the complement system may play a role in the pathophysiology of human labor. Yet no unanimous conclusion has been drawn. To compare the differences in maternal complement components C3 and C4 serum levels in cesarean section and the vaginal delivery at term and in the postpartum hemorrhage. One hundred and sixty six women delivered at term were enrolled in this study. Maternal blood samples were obtained from 47 cases of elective cesarean section and 119 cases of the vaginal delivery. Serum complement levels were measured subsequently by immuno-scatter turbidimetry. The maternal complement levels declined significantly during delivery by both the cesarean section and the vaginal delivery (p＜0.01) in comparison with the baseline. A much larger drop of C3 serum level was found in the postpartum hemorrhage and in the vaginal delivery, and the incidence of the postpartum hemorrhage has a positive correlation with the complement decline rate. The complement system may be involved in the delivery process and represents a predictive value in postpartum hemorrhage.