Complement C3 Levels Research Articles

Immunological characteristics and effect of cyclosporin in patients with immune thrombocytopenia.

ObjectiveImmune thrombocytopenia (ITP) is well‐known as an antibody‐mediated autoimmune disease, and it is easy to get response but often turns to relapse or refractory. Cyclosporin is a traditional immunosuppressant and had a good effect on ITP patients. In this paper, we retrospectively analyze the immunological characteristics and therapeutic effect of cyclosporin in 220 patients with ITP.MethodsAll newly diagnosed ITP patients in the Department of Hematology, Tianjin Medical University General Hospital from June 2018 to December 2020 were enrolled and divided into four groups according to the expression of autoantibodies and the occurrence of prodromal infection. The basic data and immune indexes of ITP patients in each group were collected. The clinical immunological characteristics of patients in each group and the therapeutic effect of cyclosporin in each group were analyzed.ResultsMulti‐autoantibody ITP patients were more likely to have low serum albumin and high gamma globulin, and the ratio of albumin to globulin decreased. In addition, the level of IgA and IgG increased and the level of complement C3 and C4 decreased more frequently than those in other groups. The number of CD3+T lymphocytes, especially CD3+CD4+T lymphocytes, decreased in ANA+ITP patients. The number of CD16+CD56+NK cells, pDC/DC ratio, and pDC/mDC ratio were higher than those in other groups. The expression of IL‐6 and the proportion of CD19+B lymphocytes increased in two groups of ITP patients with abnormal autoantibodies. The patients of pro‐infected group were more likely to suffer from coagulation disorder. After treatment with cyclosporin, the response rate increased and the 3‐month relapse rate decreased in all ITP patients, and the therapeutic effect of patients with high megakaryocyte number was significantly higher than that of patients with low megakaryocyte number. The impact factors that influence the effect of glucocorticoid and(or) IVIG were the number of CD3+CD8+T lymphocytes, CD4/CD8 cell ratio, and the number of CD19+B lymphocytes. The independent impact factor of cyclosporin therapeutic response rate was the number of CD3+T lymphocytes.ConclusionsITP is a heterogeneous disease, recurrence may occur during or rapidly after treatment. Cyclosporine included treatment can improve the effective rate of ITP and reduce the relapse rate within 3 months. The number of CD3+T lymphocytes was the only impact factor that influence the therapeutic effect of cyclosporin in ITP patients.

Chinese Herbal Medicine for Systemic Lupus Erythematosus: A Systematic Review and Meta-analysis of Randomized, Placebo-Controlled Trials

To provide evidence on the efficacy and safety of Chinese herbal medicine (CHM) as interventions for systemic lupus erythematosus (SLE). Seven electronic databases, including the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Chinese Biomedical Literature Service System (SinoMed), Wanfang, Embase, and PubMed, were comprehensively searched, from their inception to August 16, 2020, for all randomized controlled trials (RCTs) that focused on CHM used alone or in combination with conventional medicine for SLE. Outcomes were SLE activity index (SLEDAI), traditional Chinese medicine symptom/syndrome score (TCMSS), dosage of glucocorticoids, main serological testing, and incidence of adverse events. Data were extracted and pooled using Review Manager 5.3 software. A total of 13 RCTs enrolling 856 participants met our inclusion criteria. Meta-analyses showed that, compared to placebo, CHM had statistically significant effect on reducing SLEDAI score (MD=-1.74, 95% CI: -2.29 to -1.18), diminishing TCMSS (SMD=-0.89, 95% CI: -1.16 to -0.62), decreasing dosage of glucocorticoids (MD=-2.41 mg/d, 95% CI: -3.34 to -1.48), lowering erythrocyte sedimentation rate (MD=-4.78 mm/h, 95% CI: -8.86 to -0.71), and increasing serum complement C4 level (MD=0.03 mg/dL, 95% CI: 0.00 to 0.06). No significant difference was found between CHM and placebo on adverse events. CHM provided significant beneficial effect on controlling disease activity and reducing dose of glucocorticoids used among SLE patients. Future advanced designed RCTs for CHM treating moderate to severe SLE with multicenter and longer follow-up are urgently needed.

A random forest model predicts responses to infliximab in Crohn’s disease based on clinical and serological parameters

Background Infliximab (IFX) has revolutionised the treatment for Crohn’s disease (CD) recently, while a part of patients show no response to it at the end of the induction period. We developed a random forest-based prediction tool to predict the response to IFX in CD patients. Methods This observational study retrospectively enrolled the patients diagnosed with active CD and received IFX treatment at the Gastroenterology Department in Xiangya Hospital of Central South University between January 2017 and December 2019. The baseline data were recorded in the beginning and were used as predictor variables to construct models to forecast the outcome of the response to IFX. Results Our cohort identified a total of 174 patients finally with a response rate of 29.3% (51/174). The area under the receiver operating characteristic curve (AUC) for the model, based on the random forest was 0.90 (95%CI: 0.82–0.98), compared to the logistic regression model with AUC of 0.68 (95%CI: 0.52–0.85). The optimal cut-off value of the random forest model was 0.34 with the specificity of 0.94, the sensitivity of 0.81 and the accuracy of 0.85. We demonstrated a strong association of IFX response with the levels of complement C3 (C3), high density lipoprotein, serum albumin, Controlling Nutritional Status (CONUT) score and visceral fat area/subcutaneous fat area ratio (VSR). Conclusion A novel random forest model using the clinical and serological parameters of baseline data was established to identify CD patients with baseline inflammation to achieve IFX response. This model could be valuable for physicians, patients and insurers, which allows individualised therapy.

Improvement of renal and non-renal SLE outcome measures on sirolimus therapy – A 21-year follow-up study of 73 patients

The safety, tolerance, and selected renal and non-renal outcome measures were evaluated in 73 SLE patients who received sirolimus therapy for more than 3 months in our institution over the past 21 years. In 12 patients who had lupus nephritis, proteinuria (p = 0.0287), hematuria (p = 0.0232), anti-DNA antibody levels (p = 0.0028) and steroid use were reduced (p = 0.0200). In the non-renal cohort of 61 patients, anti-DNA antibody levels (p = 0.0332) and steroid use were reduced (p = 0.0163). Both in the renal and non-renal cohorts, C3 (renal p = 0.0070; non-renal p = 0.0021) and C4 complement levels were increased (renal p = 0.0063; non-renal p = 0.0042) Adverse effects of mouth sores (2/73), headaches (1/73), and gastrointestinal discomfort were noted in a minority of patients (6/73). Sirolimus was only discontinued in two of 73 patients due to headache and recurrent infections, respectively. This study suggests that sirolimus is well tolerated and exerts long-term therapeutic efficacy in controlling renal and non-renal manifestations of SLE.

Effects of Simulated Heat Wave on Oxidative Physiology and Immunity in Asian Yellow Pond Turtle (Mauremys mutica)

Global warming has led to an increase in the frequency, duration, and intensity of heat waves in the summer, which can cause frequent and acute heat stress on ectotherms. Thus, determining how ectothermic animals respond to heat waves has been attracting growing interest among ecologists. However, the physiological and biochemical responses to heat waves in reptiles, especially aquatic reptiles, are still poorly understood. The current study investigated the oxidant physiology, immunity, and expression levels of heat shock proteins (HSP) mRNA after exposure to a simulated heat wave (1 week, 35 ± 4°C), followed by a recovery period (1 week, 28 ± 4°C) in juvenile Asian yellow pond turtle (Mauremys mutica), a widely farmed aquatic turtle in East Asia. The contents of malondialdehyde (MDA) in the liver and muscle were not significantly affected by the heat wave or recovery. Of all antioxidant enzymes, only the activity of glutathione peroxidase (GSH-Px) in muscles increased after heat wave, while the total superoxide dismutase (T-SOD), catalase activity (CAT), and total antioxidant capacity (T-AOC) did not change during the study. The organo-somatic index for the liver and spleen of M. mutica decreased after the heat wave but increased to the initial level after recovery. In contrast, plasma lysozyme activity and serum complement C4 levels increased after the heat wave, returning to the control level after recovery. In addition, heat waves did not alter the relative expression of HSP60, HSP70, and HSP90 mRNA in the liver. Eventually, heat wave slightly increased the IBR/n index. Therefore, our results suggested that heat waves did not lead to oxidative damage to lipids in M. mutica, but deleteriously affected the turtles’ immune organs. Meanwhile, the constitutive levels of most antioxidative enzyme activities, HSPs and enhanced blood immune functions might protect the turtles from the threat of heat waves under the current climate scenarios.

A model incorporating serum C3 complement levels may be useful for diagnosing biliary atresia in infants

IntroductionCorrectly identifying patients with biliary atresia (BA), while avoiding invasive diagnostic methods is challenging. The purpose of this study was to determine the value of serum immune indicators for distinguishing BA from other causes of cholestasis in infants. Patients and methodsThe data of infants with a surgical/histological diagnosis of BA and those with other causes of cholestatic jaundice were retrospectively analyzed. Patients were divided into a BA group and a cholestasis control (CC) group. Biochemical parameters, major lymphocyte subsets, immunoglobin and C3 and C4 complement levels were compared between the groups. ResultsA total of 129 infants with BA and 63 with other causes of cholestasis (CC control group) with a median age of 2.2 months were included in the analysis. The levels of CD3+ T cells, CD3+CD4+ T cells, and premature T cells and the levels of C3 and C4 were all significantly higher in the BA group compared to the CC group (all P<0.05). Pair-wise correlation analyses indicated that C3 and C4 had a significant positive correlation with γ-GT in the BA group, but not in the CC group. Five indices were found to be significantly associated with BA: stool color, globulin, γ-GT, C3 and C4. A model incorporating stool color, gamma-glutamyl transpeptidase level, and C3 level exhibited an area under the ROC curve (AUC) of 0.93, and a sensitivity of 93% and specificity of 83% for the diagnosis of BA. ConclusionsModels incorporating serum C3 levels may be useful for accurately diagnosing BA in infants.

Cross-sectional study of plasma Axl, ferritin, IGFBP4 and sTNFR2 as biomarkers of disease activity in childhood-onset SLE: A study of the Pediatric Nephrology Research Consortium.

To evaluate the performance of 4 plasma protein markers for detecting disease activity in childhood-onset systemic lupus erythematosus (SLE) patients. Eighty-three consecutive pediatric patients fulfilling ≥4 ACR criteria for SLE and twenty-five healthy controls were prospectively recruited for serological testing of 4 protein markers identified by antibody-coated microarray screen, namely Axl, ferritin, IGFBP4 and sTNFR2. SLE disease activity was assessed using SLEDAI-2000 score. Fifty-seven patients had clinically active SLE (SLEDAI score ≥4, or having a flare). The plasma concentrations of Axl and ferritin were significantly higher in patients with active SLE than inactive SLE. Plasma Axl levels were significantly higher in active renal versus active non-renal SLE patients. Levels of Axl, ferritin and IGFBP4 correlated significantly with SLEDAI scores. Levels of Axl, IFGBP4 and sTNFR2 inversely correlated with plasma complement C3 levels. Only plasma Axl and ferritin levels correlated with degree of proteinuria. These markers were more specific, but less sensitive, in detecting concurrent SLE activity than elevated anti-dsDNA antibody titer or decreased C3. Ferritin and IGFBP4 levels were more specific for concurrent active lupus nephritis than anti-dsDNA or C3. Plasma ferritin was the best monitor of global SLE activity, followed by C3 then Axl, while both Axl and C3 were best monitors of clinical lupus nephritis activity. In childhood-onset SLE patients, plasma ferritin and Axl perform better than traditional yardsticks in identifying disease activity, either global or renal. The performance of these plasma markers should be explored further in longitudinal cohorts of SLE patients.

Dose-effect relationship between serum polycyclic aromatic hydrocarbon adducts and serum complements among children in a city of East China

Objective: To investigate the dose-response relationship between serum polycyclic aromatic hydrocarbon adducts and serum complement C3 and C4 levels among children from a city in East China. Methods: In September 2016, two boarding schools in the air pollution exposure area and the control area (beyond the upwind of 30 km in the air pollution exposure area) in a city in East China were selected as the research site, and the eligible school-age children were recruited as the research objects. A total of 273 children were included, including 163 in the exposure group and 110 in the control group. The annual air pollutant data (PM2.5, PM10 and NO2) of the two regions during the study period were collected. The exposure level of tobacco was evaluated by cotinine in urine. The levels of serum complement C3 and C4 were determined by automatic biochemical analyzer. The serum anti-7, 8, -dihydrodiol-9, 10-epoxide benzo[a]pyrene (BPDE)-albumin adduct levels were detected by ELISA. Linear regression model was used to explore the dose-response relationship between BPDE-albumin adducts and serum complement C3 and C4. Results: The age of 273 subjects was (13.67±0.37) years old, including 165 boys (60.4%). The average annual exposure levels of PM2.5, PM10 and NO2 and the level of serum BPDE-albumin adducts in the exposure group were higher than those in the control group (P<0.05). The results of linear regression model analysis showed that after adjusting age, sex, BMI z-score and urinary cotinine level, when the serum BPDE-albumin adduct level increased by 10%, the serum complement C4 level decreased by 1.2% (P=0.017). After adjusting age, BMI z-score and urinary cotinine level, for every 10% increase in serum BPDE-albumin adduct level in boys, the serum complement C4 level decreased by 1.68% (P=0.024). After adjusting age, sex and BMI z-score, the levels of serum complement C3 and C4 decreased by 1.31% and 3.57% respectively for every 10% increase in serum BPDE-albumin adducts among children in the urinary cotinine detection group (P<0.05). Conclusion: There is a significant dose-response relationship between serum BPDE-albumin adducts and the complement C4 among children.

Interferon-α activates interleukin-1 receptor-associated kinase 1 to induce regulatory T-cell apoptosis in patients with systemic lupus erythematosus.

Impaired regulatory T-cell (Treg) responses and upregulated interleukin-1 receptor-associated kinase 1 (IRAK1) expression are associated with the development of human systemic lupus erythematosus (SLE). Here, we show that the levels of upregulated IRAK1 expression in circulating Tregs are correlated with the percentages of apoptotic Tregs, Systemic Lupus Erythematosus Disease Activity Index scores, and serum complement C3 levels in SLE patients. High levels of plasma interferon (IFN)-α in SLE patients induced IRAK1 phosphorylation to trigger Treg apoptosis, which was mitigated by IRAK1 inhibitor (IRAK-Inh) treatment. Bioinformatics indicated that IRAK1 activation was related to the IFN-α/β and mitogen-activated protein kinase (MAPK) signaling in Tregs and IFN-α treatment induced the p38 and MAPK/ERK kinase 3/6 phosphorylation, which was attenuated by IRAK-Inh in Tregs. Treatment with IRAK-Inh effectively alleviated renal injury and promoted the survival of lupus-prone B6.MRL-Faslpr /Nju mice. Therefore, IFN-α induced IRAK1 activation to promote Treg apoptosis, contributing to the pathogenesis of SLE and IFN-α/IRAK1 may be therapeutic targets for SLE.

Study on the effect of integrated traditional Chinese and western medicine in the treatment of brucellosis

Objective: To observe the clinical effect of integrated traditional Chinese and western medicine on brucellosis and its influence on humoral immune indexes. Methods: In October 2019, 169 cases of brucellosis hospitalized in Tianjin Second People's Hospital were selected as the research objects, and divided into two groups according to the random number method, 84 cases in the integrated treatment group and 85 cases in the western medicine treatment group. The western medicine treatment group was given antibiotics and other routine western medicine support treatment. The integrated treatment group was given traditional Chinese medicine for treatment based on syndrome differentiation, on the basis of western medicine treatment group, and 6 weeks was a course of treatment. The clinical efficacy and Traditional Chinese Medicine (TCM) syndrome scores were compared between the two groups of patients after treatment, and the changes in humoral immune indexes, biochemical, and liver and kidney functions of the patients before and after treatment were analyzed. Results: The total effective rate was 100.00% (84/84) in the integrated treatment group and 97.65% (83/85) in the western medicine treatment group. The difference was not statistically significant (P>0.05) . The difference was not statistically significant (P>0.05) . There was no statistically significant difference in TCM syndrome scores between the two groups before treatment (P>0.05) , and the TCM syndrome scores after treatment were lower than before treatment (P<0.05) . Among them, the TCM syndrome scores of the integrated treatment group were lower than those of the western medicine treatment group (P<0.05) . There was no significant difference in IgG, IgA, IgM, C3, C4, miRNA-155, C-reactive protein (CRP) , erythrocyte sedimention rate (ESR) , alanine aminotransferase (ALT) and aspartate aminotransferase (AST) between the two groups before treatment (P>0.05) . After treatment, IgG, IgA, IgM, miRNA-155, CRP, ESR, ALT and AST were all lower than before treatment, and C3 and C4 complement levels were higher than before treatment (P<0.05) . Among them, IgG, IgA, IgM, miRNA-155, CRP, ESR, ALT and AST in the integrative treatment group were all lower than the western medicine treatment group, while the C3 and C4 complement levels were higher than the western medicine treatment group (P<0.05) . Conclusion: The treatment of brucellosis with integrated traditional Chinese and western medicine can significantly improve the TCM syndrome score and reduce the levels of CRP and ESR. The mechanism of action may be related to the regulation of the patient's humoral immunological indicators.

A patient with a homozygous diacylglycerol kinase epsilon (DGKE) gene mutation with atypical haemolytic uraemic syndrome and low C3 responded well to eculizumab: a case report

BackgroundAtypical haemolytic uraemic syndrome (aHUS) is a rare systemic syndrome characterized by non-immune haemolytic anaemia, thrombocytopenia, and kidney injury. In most cases, alternative complement pathway dysregulation is the identifying cause. Recently, other genetic causes have been identified, including a mutation in the diacylglycerol kinase epsilon (DGKE) gene, which theoretically affect the coagulation pathway and does not affect the complement pathway. Data about the management of these patients are limited. Ideal management and definitive treatment protocols have not yet been established.Case presentationA three-year-old boy presented with features of atypical haemolytic uraemic syndrome (aHUS) and low complement C3. He was presumed to have complement-mediated aHUS and was managed empirically with eculizumab. Two weeks after starting eculizumab, his haemoglobin levels, platelet count, and complement C3 level normalized but he continued to have non-nephrotic range proteinuria. His genetic testing revealed a homozygous DGKE mutation, with no other mutation detected. Six months after presentation, the patient was still in remission with no features of aHUS, a trial of weaning eculizumab by increasing dose interval was followed by nephrotic range proteinuria and severe oedema. His proteinuria improved and his oedema resolved after resuming his recommended eculizumab dose.ConclusionsDGKE gene mutation can lead to aHUS with theoretically no complement dysregulation. However, some patients with this mutation show alternative complement pathway activation. This case report describes a patient with aHUS due to a DGKE gene mutation and low C3 levels who responded to eculizumab, adding to the previously reported cases of patients with DGKE gene mutations who had complete remission with no relapse with C5 blockers and/or plasma exchange. A randomized controlled study on patients with DGKE mutations might be beneficial in understanding the disease and generating a management protocol.

Complement C3 identified as a unique risk factor for disease severity among young COVID-19 patients in Wuhan, China

Given that a substantial proportion of the subgroup of COVID-19 patients that face a severe disease course are younger than 60 years, it is critical to understand the disease-specific characteristics of young COVID-19 patients. Risk factors for a severe disease course for young COVID-19 patients and possible non-linear influences remain unknown. Data were analyzed from COVID-19 patients with clinical outcome in a single hospital in Wuhan, China, collected retrospectively from Jan 24th to Mar 27th. Clinical, demographic, treatment and laboratory data were collected from patients' medical records. Uni- and multivariable analysis using logistic regression and random forest, with the latter allowing the study of non-linear influences, were performed to investigate the clinical characteristics of a severe disease course. A total of 762 young patients (median age 47 years, interquartile range [IQR] 38–55, range 18–60; 55.9% female) were included, as well as 714 elderly patients as a comparison group. Among the young patients, 362 (47.5%) had a severe/critical disease course and the mean age was statistically significantly higher in the severe subgroup than in the mild subgroup (59.3 vs. 56.0, Student's t-test: p < 0.001). The uni- and multivariable analysis suggested that several covariates such as elevated levels of serum amyloid A (SAA), C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased lymphocyte counts influence disease severity independently of age. Elevated levels of complement C3 (odds ratio [OR] 15.6, 95% CI 2.41–122.3; p = 0.039) are particularly associated with the risk of developing severe COVID-19 specifically in young patients, whereas no such influence seems to exist for elderly patients. Additional analysis suggests that the influence of complement C3 in young patients is independent of age, gender, and comorbidities. Variable importance values and partial dependence plots obtained using random forests delivered additional insights, in particular indicating non-linear influences of risk factors on disease severity. This study identified increased levels of complement C3 as a unique risk factor for adverse outcomes specific to young COVID-19 patients.

ASSESSMENT OF THE SERUM LEVEL OF COMPLEMENT C3 AND C4 IN CHRONIC VIRAL HEPATITIS C INFECTION AND THEIR CORRELATION WITH RESPONSE TO DIRECT ACTING ANTI-VIRAL AGENTS

Background: The interactions between hepatitis C Virus (HCV) and the host immune system have a major role in HCV pathogenesis. Objective: To estimate complement C3 and C4 serum levels in patients with chronic HCV patients and to correlate its levels with response to directly acting anti-viral agents (DAAs) in those patients. Patients and methods: The study included 80 individuals classified into two groups: Group (I): 40 patients with chronic HCV infection, Group (II): Control group which included 40 healthy individuals. Measurement of the level of complement C3 and C4 has done by nephelometry immunoassay before and after treatment with DAAs. Results: All patients with chronic HCV infection in group (I) showed significant reduction in serum levels of complement C3 and C4 compared to the control group (II). Moreover, those patients who treated with DAAs showed significantly higher levels of C3 and C4 when compared to chronic HCV patients before treatment with DAAs. Conclusion: Serum levels of complement C3 and C4 serum may be used in the follow up of the course of the disease and may be used as a predictor for the response to treatment with DAAs.

Disease Damage Accrual and Low Bone Mineral Density in Female Patients with Systemic Lupus Erythematosus.

Osteoporosis is a common comorbidity in patients with systemic lupus erythematosus (SLE), but the potential contribution of disease-associated factors to bone status in SLE is not well known because the reported risk factors from different studies differ greatly. We aimed to examine frequency of reduced bone mass in women with SLE, and determine their potential associations with disease activity, damage accrual and SLE-related clinical markers. A cross-sectional study including 121 Caucasian pre-menopausal and postmenopausal women was conducted (mean age 49.2 ± 12.4 years). The SLE Disease Activity Index (SLEDAI-2 K) and the SDI Damage Index were used to assess disease activity and disease-related damage, respectively. Bone mineral density (BMD) of the left femoral neck and lumbar spine (L2-L4) were measured by dual-energy X-ray absorptiometry. Ten patients (8.3%) had osteoporosis, 63 (52.1%) patients had osteopenia and 6.8% of women had history of previous fracture. Patients with low bone mass had a significantly higher mean SDI (1.3 ± 1.2 versus 0.7 ± 1.0 p = 0.003). T-score at lumbar spine was inversely correlated with SDI score (r = -0.222, p = 0.014) and complement C3 level (r = -0.206, p = .024). SDI scores were significantly different between patients with osteoporosis, osteopenia, and normal BMD after adjusting for covariates (p = .004). There is a high prevalence of low BMD in Caucasian women with SLE, and this status was associated with higher damage accrual scores, supporting that disease damage may itself be a major contributor to the low BMD. Women with SLE with organ damage require regular bone status monitoring to prevent further musculoskeletal damage.

Characteristics of immune function in the acute phase of Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP) is still diagnosed using symptoms and signs together with some histopathological findings. The purpose of this study was to summarize the characteristics and roles of cellular and humoral immunity in children with Henoch-Schönlein purpura (HSP). A total of 502 cases of patients with acute HSP were diagnosed and observed. The levels of T lymphocyte subsets, natural killer cells (NK cells), and B cells were analyzed by flow cytometry. The serum immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), and complement C3 (C3) and complement C4 (C4) levels were detected by velocity scatter turbidimetry. Compared with the healthy groups, the levels of cluster of differentiation 3 (CD3), cluster of differentiation 4 (CD4), B cells, and NK cells and ratio of CD4/CD8 in patients with HSP were decreased (P < 0.05). The levels of IgG, IgA, IgM, and C3 were increased (P < 0.05). Compared with the Kawasaki disease (KD) group, the levels of CD3, CD4, CD8, B cells, NK cells, and IgA in patients with HSP were increased (P < 0.05), and the ratio of CD4/CD8 and levels of IgM, C3, and C4 was decreased (P < 0.05). Compared with the pneumonia group, the levels of CD3, CD4, B cells, and IgA in patients with HSP were increased (P < 0.05), and the ratio of CD4/CD8 and levels of IgM and C4 was decreased (P < 0.05). Cellular immunity and humoral immunity were all involved in the pathogenesis of HSP. The decline of NK cells, B lymphocyte cells, CD3, CD4 the increased secretion of immunoglobulin, and the abnormal appearance of IgA and C3 may exist during the progression. It may indicate a worse prognosis and increasing the risk of dedifferentiation. Cellular immunity was lower, which lead to increased production of inflammatory mediators and increased secretion of immunoglobulin, which then mediated systemic small-vessel vasculitis. Key Points • The pathogenesis of Henoch-Schönlein purpura (HSP) was not completely illuminated. • There was a lack of disease-specific laboratory abnormalities that can be used in the clinical diagnosis of HSP. • We compared the laboratory abnormalities in the immune system of HSP with KD and pneumonia. • Cellular immunity and humoral immunity were all involved in the pathogenesis of HSP. Cellular immunity was lower, which lead to the following pathological changes.

Peripheral immune profile of children with Talaromyces marneffei infections: a retrospective analysis of 21 cases

BackgroundTalaromyces marneffei (T. marneffei) is an opportunistic pathogen that infects immunodeficient children. The aim of the study is to determine the clinical features and peripheral immune state of Talaromyces marneffei (T. marneffei) infections in children for early detection and diagnosis.MethodsWe retrospectively reviewed 21 pediatric patients who were diagnosed with T. marneffei infections and were followed up in the Guangzhou Women and Children’s Medical Center from January 2010 to January 2020. For each patient, we collected and analyzed clinical characteristics, peripheral immunological results, genetic tests, complications and prognosis.ResultsCommon clinical features of the patients included fever (20/21, 95.24%), cough (17/21, 80.95%) and hepatomegaly (17/21, 80.95%). Severe complications included septic shock (12/21, 57.14%), hemophagocytic lymphohistiocytosis (HLH) (11/21, 52.38%), acute respiratory distress syndrome (ARDS) (10/21, 47.62%), multiple organ dysfunction syndrome (MODS) (9/21, 42.86%), and disseminated intravascular coagulation (DIC) (7/21, 33.33%). Eleven children (11/21, 52.38%) eventually died of T. marneffei infections. All patients were HIV negative. Seven cases revealed reduced antibody levels, especially IgG. Higher levels of IgE were detected in 9 cases with an obvious increase in two patients. Ten patients showed decreased complement C3 levels, some of whom had low C4 levels. Three patients displayed decreased absolute T lymphocyte counts, including the CD 4+ and CD 8+ subsets. A reduction in NK cells was present in most patients. No patient had positive nitro blue tetrazolium (NBT) test results. Nine patients were screened for common genetic mutations. Of the cases, one case had no disease-specific gene mutation. Four children had confirmed hyperimmunoglobulin M syndrome (HIGM) with CD40LG variation, one case had severe combined immunodeficiency (SCID), and one case had hyper-IgE syndrome (HIES). One patient was identified as having a heterozygous mutation in STAT3 gene; however, he showed no typical clinical manifestations of HIES at his age. One patient had a mutated COPA gene with uncertain pathogenic potential. Another patient was diagnosed with HIES that depended on her clinical features and the National Institutes of Health (NIH) scoring system.ConclusionsT. marneffei infections in HIV-negative children induced severe systemic complications and poor prognosis. Children with T. marneffei infections commonly exhibited abnormal immunoglobulin levels in peripheral blood, particularly decreased IgG or increased IgE levels, further suggesting possible underlying PIDs in these patients.

MALDI-TOF Protein Profiling Reflects Changes in Type 1 Diabetes Patients Depending on the Increased Amount of Adipose Tissue, Poor Control of Diabetes and the Presence of Chronic Complications.

Introduction: Protein profiling allows the determination of the presence of proteins marking various stages of the disease, and differentiates between people at risk of various diseases. In type 1 diabetes, protein profiling had been previously used to find blood markers other than islet autoantibodies to indicate the pancreatic beta cell destruction process and to reflect the progression of type 1 diabetes mellitus (T1DM). However, T1DM is an auto-immune disease and its clinical presentation changes in time of its duration. The aim of the study: To find differences in protein profiles in patients with type 1 diabetes according to diabetes control (HbA1c > 7%) and with presence of diabetic complications or obesity. It may help to identify subgroups of patients who may need a better clinical supervision and individualized treatment. Material and methods: A group of 103 patients with auto-immunologically confirmed T1DM, and meeting the following inclusion criteria: Caucasian race, duration of diabetes >5 years, were used in the study. Criteria of exclusion: past or present cancer (treated with chemo-/radiotherapy), diseases of the liver (ALT > 3 × ULN) except for people with simple hepatic steatosis, chronic renal disease (eGFR < 30 mL/1.73 m2/min), and acute inflammation (CRP > 5 mg/dL). The study group was divided in terms of the presence of chronic complications, obesity, or poor metabolic control (HbA1c > 7%). Protein profiling was completed by using the MALDI-TOF MS (matrix-assisted laser desorption/ionization-time of flight mass spectrometry) analyzer. Results: Differentiating proteins were identified in all of the groups. The groups burdened with complications, obesity, and poor metabolic control were characterized by increased levels of fibrinogen, complement C4 and C3. Conclusion: The groups of type 1 diabetes patients burdened with complications, obesity, and poor metabolic control were characterized by increased levels of fibrinogen, complement C4 and C3. Further detailed studies are necessary to determine more subtle changes in the proteomic profile of patients with type 1 diabetes.

Changes in the growth, ileal digestibility, intestinal histology, behavior, fatty acid composition of the\xa0breast muscles, and blood biochemical parameters of broiler chickens by dietary inclusion of safflower oil and vitamin C

BackgroundThe effects of safflower oil and vitamin C (Vit. C) inclusion in broiler chicken diets on the growth performance, apparent ileal digestibility coefficient “AID%” of amino acids, intestinal histology, behavior, carcass traits, fatty acid composition of the breast muscle, antioxidant and immune status for a 35-day feeding period were evaluated. A total of 300 three-day-old Ross chicks (58.25 g ± 0.19) were randomly allotted in a 2 × 3 factorial design consisting of two levels of vitamin C (0 and 400 mg/kg diet) and three levels of safflower oil (0, 5, and 10 g/kg diet).ResultsAn increase in the final body weight, total body weight gain, total feed intake, and the relative growth rate (P < 0.05) were reported by safflower oil and vitamin C inclusion. Dietary supplementation of safflower oil and vitamin C had a positive effect (P < 0.05) on the ingestive, resting, and feather preening behavior. Vitamin C supplementation increased (P < 0.05) the AID% of lysine, threonine, tryptophan, arginine, and valine. Safflower inclusion (10 g/kg) increased (P < 0.05) the AID% of methionine and isoleucine. Safflower oil inclusion increased (P < 0.05) the levels of stearic acid, linoleic acid, saturated fatty acids, and omega-3 fatty acids (ω-3) in the breast muscle. In contrast, the supplementation of only 10 g of safflower oil/kg diet increased (P = 0.01) the omega-3/omega-6 (ω-3/ω-6) fatty acids ratio. Vit. C supplementation increased (P < 0.05) the CAT serum levels, SOD, and GSH enzymes. Dietary supplementation of safflower oil and vitamin C improved the intestinal histology. They increased the villous height and width, crypt depth, villous height/crypt depth ratio, mucosal thickness, goblet cell count, and intra-epithelium lymphocytic lick cell infiltrations. The serum levels of IgA and complement C3 were increased (P < 0.01) by Vit. C supplementation and prominent in the 400 vit. C + 10 safflower Oil group.ConclusionA dietary combination of safflower oil and vitamin C resulted in improved growth rate, amino acids AID%, intestinal histology, welfare, immune and antioxidant status of birds, and obtaining ω-3 and linoleic acid-enriched breast muscles. The best inclusion level was 400 vit. C + 10 safflower Oil.

Cell Wall Components of Bacillus pumilus SE5 Improved the Growth, Digestive and Immunity of Grouper (Epinephelus coioides)

Background:: Probiotic cellular components could be an interesting alternative to live probiotics, which could potentially cause safety problems in open aquatic environments. Objective:: The cell wall (CW), peptidoglycan (PG) and lipoteichoic (LTA) were extracted from probiotic strain of Bacillus pumilus SE5, and these biomolecules were used to develop the possible application in fish aquaculture. Methods:: Grouper (Epinephelus coioides) juveniles were fed with either a basal control diet or the basal diet supplemented with CW, PG and LTA respectively for 60 days, and the growth performance, digestive enzymes activities, serum immune responses and immune genes expression in head kidney were determined. Results:: Dietary supplement PG and LTA significantly improved final body weight (FBW), weight gain rate (WGR), specific growth rate (SGR) and protein efficiency ratio (PER), while significantly decreased feed conversion ratio (FCR) was noticed in all the treatments compared with the control group. Dietary supplements of CW, PG and LTA enhanced the activities of trypsin, lipase and amylase in the liver. Serum complement C3 and IgM levels as well as, AKP, ACP and SOD activities elevated significantly in fish fed the PG and LTA containing diets. Furthermore, PG and LTA containing diets, significantly up-regulated expression of TLR2, NOD2, IL-8, IgM and three antibacterial peptides genes (epinecidin-1, hepcidin-1 and β-defensin) in the head kidney. Conclusion:: PG and LTA originated from probiotic B. pumilus SE5 could effectively enhance the growth performance, feed utilization, digestive ability and boost innate and adaptive immune system of E. coioides.

Predictors of hematologic malignancy relapse in patients with advanced chronic graft-versus-host disease.

Malignancy relapse remains a major barrier to treatment success in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Chronic graft-versus-host disease (cGVHD) markedly reduces hematologic malignancy relapse risk, but relapses still occur in these patients.Patients (n=275) with moderate or severe cGVHD were enrolled on the National Cancer Institute (NCI) prospective cross-sectional natural history study (NCT00092235). Subjects were median 36 months after allo-HSCT and were followed subsequently for malignancy relapse and survival.Seventeen patients experienced relapse. In a multivariable model including time-dependent influences on relapse, risk factors associated with increased risk of relapse included shorter time from transplant to cGVHD evaluation (HR 0.279, 95% CI 0.078-0.995) and lower number of prior lines of systemic immunosuppressive therapy for cGVHD (HR 0.260, 95% CI 0.094-0.719). In a model excluding time-dependent influences on relapse risk, lower number of prior lines of systemic immunosuppressive therapy for cGVHD (HR 0.288, 95% CI 0.103-0.804), lower C4 complement level (HR 0.346, 95% CI 0.129-0.923), and higher body mass index (HR 3.222, 95% CI 1.156-8.974), were all associated with increased relapse risk.Parameters indicating cGVHD severity and activity are associated with risk of malignancy relapse. Classical predictors of relapse after allo-HSCT do not seem to be prognostic.