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Frontiers in Immunology 2022It is generally believed that complement system is strongly associated with the risk of nonalcoholic fatty liver disease (NAFLD). However, complement system contains a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It is generally believed that complement system is strongly associated with the risk of nonalcoholic fatty liver disease (NAFLD). However, complement system contains a variety of complement components, and the relationship between complement components and the risk and severity of NAFLD is inconsistent. The aim of this meta-analysis was to evaluate the association of complement components with the risk and severity of NAFLD.
METHODS
We searched PubMed, Embase, Cochrane Library, Google Scholar, Scopus, and ZhiWang Chinese databases from inception to May 2022 for observational studies reporting the risk of NAFLD with complement components. Random-effects meta-analysis was used to obtain pooled estimates of the effect due to heterogeneity.
RESULTS
We identified 18 studies with a total of 18560 included subjects. According to recent studies, levels of complement component 3 (C3) (mean difference (MD): 0.43, 95% confidence interval (CI) 0.26-0.60), complement component 4 (C4) (MD: 0.04, 95% CI 0.02-0.07), complement component 5(C5) (MD: 34.03, 95% CI 30.80-37.27), complement factor B (CFB) (MD: 0.22, 95% CI 0.13-0.31) and acylation stimulating protein (ASP) (standard mean difference (SMD): 5.17, 95% CI 2.57-7.77) in patients with NAFLD were significantly higher than those in the control group. However, no statistical significance was obtained in complement factor D (CFD) levels between NAFLD and non-NAFLD (MD=156.51, 95% CI -59.38-372.40). Moreover, the levels of C3, C5, CFB, and ASP in patients with moderate and severe NAFLD were significantly higher than those in patients with mild NAFLD. Except for C4 and CFD, the included studies did not explore the changes in the severity of NAFLD according to the concentration of C4 and CFD.
CONCLUSIONS
This meta-analysis demonstrates that an increase in complement components including C3, C5, CFB, and ASP is associated with an increased risk and severity of NAFLD, indicating that they may be good biomarkers and targets for the diagnosis and treatment of NAFLD.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO [https://www.crd.york.ac.uk/PROSPERO/], identifier CRD42022348650.
Topics: Humans; Biomarkers; Complement Factor B; Immunologic Factors; Non-alcoholic Fatty Liver Disease
PubMed: 36569882
DOI: 10.3389/fimmu.2022.1054159 -
Frontiers in Immunology 2021Activation of the complement system has been observed in coronavirus disease 19 (COVID-19). We conducted a systematic review and meta-analysis with meta-regression to... (Meta-Analysis)
Meta-Analysis
Activation of the complement system has been observed in coronavirus disease 19 (COVID-19). We conducted a systematic review and meta-analysis with meta-regression to investigate possible differences in the serum concentrations of two routinely measured complement components, C3 and C4, in COVID-19 patients with different severity and survival status. We searched PubMed, Web of Science and Scopus, between January 2020 and February 2021, for studies reporting serum complement C3 and C4, measures of COVID-19 severity, and survival. Eligibility criteria were a) reporting continuous data on serum C3 and C4 concentrations in COVID-19 patients, -b) investigating COVID-19 patients with different disease severity and/or survival status, c) adult patients, d) English language, e) ≥10 patients, and f) full-text available. Using a random-effects model, standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated to evaluate differences in serum C3 and C4 concentrations between COVID-19 patients with low vs. high severity or survivor vs. non-survivor status. Risk of bias was assessed using the Newcastle-Ottawa scale whereas publication bias was assessed with the Begg's and Egger's tests. Certainty of evidence was assessed using GRADE. Nineteen studies in 3,764 COVID-19 patients were included in the meta-analysis. Both C3 and C4 concentrations were significantly lower in patients with high disease severity or non-survivor status than patients with low severity or survivor status (C3 SMD=-0.40, 95% CI -0.60 to -0.21, p<0.001; C4 SMD=-0.29, 95% CI -0.49 to -0.09, p=0.005; moderate certainty of evidence). Extreme between-study heterogeneity was observed (C3, I = 82.1%; C4, I = 84.4%). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not modified. There was no publication bias. In meta-regression, the SMD of C3 was significantly associated with white blood cell count, C-reactive protein (CRP), and pro-thrombin time, whereas the SMD of C4 was significantly associated with CRP, pro-thrombin time, D-dimer, and albumin. In conclusion, lower concentrations of C3 and C4, indicating complement activation, were significantly associated with higher COVID-19 severity and mortality. C3 and C4 might be useful to predict adverse clinical consequences in these patients. PROSPERO, Registration number: CRD42021239634.
Topics: Biomarkers; COVID-19; Complement Activation; Complement C3; Complement C4; Humans; SARS-CoV-2; Severity of Illness Index
PubMed: 34163491
DOI: 10.3389/fimmu.2021.696085 -
Schizophrenia Research Aug 2020There is renewed focus on the complement system in the pathogenesis of schizophrenia. In addition to providing aetiological insights, consistently dysregulated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is renewed focus on the complement system in the pathogenesis of schizophrenia. In addition to providing aetiological insights, consistently dysregulated complement proteins in serum or plasma may have clinical utility as biomarkers.
METHODS
We performed a systematic literature review searching PubMed, Embase and PsycINFO for studies measuring complement system activity or complement protein concentrations in serum or plasma from patients with schizophrenia compared to controls. Random-effects meta-analyses were performed to calculate pooled effect estimates (Hedges' g standardised mean difference [SMD]) for complement proteins whose concentrations were measured in three or more studies. The review was pre-registered on the PROSPERO database (CRD42018109012).
RESULTS
Database searching identified 1146 records. Fifty-eight full-text articles were assessed for eligibility and 24 studies included. Seven studies measured complement system activity. Activity of the classical pathway did not differ between cases and controls in four of six studies, and conflicting results were noted in two studies of alternative pathway activity. Twenty studies quantified complement protein concentrations of which complement components 3 (C3) and 4 (C4) were measured in more than three studies. Meta-analyses showed no evidence of significant differences between cases and controls for 11 studies of C3 (SMD 0.04, 95% confidence interval [CI] -0.29-0.36) and 10 studies of C4 (SMD 0.10, 95% CI -0.21-0.41).
CONCLUSIONS
Serological studies provide mixed evidence regarding dysregulation of the complement system in schizophrenia. Larger studies of a longitudinal nature, focusing on early phenotypes, could provide further insights regarding the potential role of the complement system in psychotic disorders.
Topics: Biomarkers; Complement System Proteins; Humans; Psychotic Disorders; Schizophrenia
PubMed: 32456884
DOI: 10.1016/j.schres.2020.05.036 -
Kidney International Reports Feb 2024IgA nephropathy's (IgAN's) MEST-C classification relationship with complement activation is still not fully understood because of limited and conflicting evidence. Our...
INTRODUCTION
IgA nephropathy's (IgAN's) MEST-C classification relationship with complement activation is still not fully understood because of limited and conflicting evidence. Our study aimed to delineate this relationship through a systematic review.
METHODS
We adhered to the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines and conducted a systematic review, utilizing databases like MEDLINE (PubMed), Embase, Scopus, and Cochrane from January 2016 (year of updated MEST-C classification) to January 2023. We specifically selected studies that employed established methods to evaluate complement activation and the MEST-C classification.
RESULTS
A total of 34 studies with 10,082 patients were included. Among these, 7 studies focused on the pediatric population (500 patients), and 22 studies involved 8128 patients from Asian populations. C4d, C3, C5b9, MBL, C4, and factor H-related protein 5 (FHR5) were the most frequently studied complement proteins in relation to the MEST-C classification. Complement activation assessment was primarily conducted using immunofluorescence and immunohistochemistry on kidney biopsy specimens. All complement proteins investigated showed associations with the C1-2 class. Notably, FB, FH, MASP1/3, MASP2, C5a, and C5b9 from the alternative, lectin, and terminal pathways were uniquely present in the C1-2 class. Whereas C3, FHR5, C4, and C4d were associated with all the MEST-C classes.
CONCLUSION
We found evidence supporting the involvement of alternative and lectin complement pathways across all MEST-C classes. All examined complement factors were associated with the C1-2 class, emphasizing the critical role of complement activation, possibly at the endothelial surface. These findings may guide the development of personalized treatment strategies targeting complement pathways in relation to the MEST-C lesions.
PubMed: 38344730
DOI: 10.1016/j.ekir.2023.11.005 -
PLoS Neglected Tropical Diseases Oct 2022Malaria and filariasis are significant vector-borne diseases that are co-endemic in the same human populations. This study aims to collate the evidence, probability, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malaria and filariasis are significant vector-borne diseases that are co-endemic in the same human populations. This study aims to collate the evidence, probability, and characteristics of malaria and filariasis co-infections in participants among studies reporting the co-occurrence of both diseases.
METHODS
We searched for potentially relevant articles reporting the co-occurrence of malaria and filariasis in five electronic databases (Embase, PubMed, Scopus, Medline, and CENTRAL) from inception to May 22, 2022. We estimated the pooled prevalence and probability of malaria and filariasis co-infections among study participants using random-effects meta-analyses and synthesized the characteristics of patients with co-infections narratively.
RESULTS
We identified 951 articles, 24 of which (96,838 participants) met eligibility criteria and were included in the systematic review. Results of the meta-analysis showed a pooled prevalence of malaria and filariasis co-infections among participants of 11%. The prevalence of co-infections was 2.3% in Africa, 0.2% in Asia, and 1.6% in South America. The pooled prevalences of malaria and Wuchereria bancrofti, malaria and Loa loa, malaria and Mansonella perstans co-infections were 0.7%, 1.2%, and 1.0%, respectively. The meta-analysis results showed that the co-infections between two parasites occurred by probability (P = 0.001). Patients with co-infections were at increased risk of having an enlarged spleen, a lower rate of severe anemia, lower parasite density, and more asymptomatic clinical status. Patients with co-infections had decreased levels of C-X-C motif chemokine 5, tumor necrosis factor-α, interleukin-4, c4 complement, and interleukin-10. In addition, patients with co-infections had a lower interleukin-10/tumor necrosis factor-α ratio and higher interleukin-10/interleukin-6 ratio.
CONCLUSION
The present study showed that the prevalence of malaria and filariasis co-infections was low and varied between geographical areas in the selected articles. Co-infections tended to occur with a low probability. Further studies investigating the outcomes and characteristics of co-infections are needed.
Topics: Animals; Humans; Prevalence; Interleukin-10; Interleukin-4; Coinfection; Tumor Necrosis Factor-alpha; Interleukin-6; Filariasis; Mansonelliasis; Malaria; Probability; Complement C4; Chemokines
PubMed: 36269701
DOI: 10.1371/journal.pntd.0010857 -
Annals of Biomedical Engineering Dec 2022Knowledge of spinal kinematics is essential for the diagnosis and management of spinal diseases. Distinguishing between physiological and pathological motion patterns... (Review)
Review
Knowledge of spinal kinematics is essential for the diagnosis and management of spinal diseases. Distinguishing between physiological and pathological motion patterns can help diagnose these diseases, plan surgical interventions and improve relevant tools and software. During the last decades, numerous studies based on diverse methodologies attempted to elucidate spinal mobility in different planes of motion. The authors aimed to summarize and compare the evidence about cervical spine kinematics under healthy and degenerative conditions. This includes an illustrated description of the spectrum of physiological cervical spine kinematics, followed by a comparable presentation of kinematics of the degenerative cervical spine. Data was obtained through a systematic MEDLINE search including studies on angular/translational segmental motion contribution, range of motion, coupling and center of rotation. As far as the degenerative conditions are concerned, kinematic data regarding disc degeneration and spondylolisthesis were available. Although the majority of the studies identified repeating motion patterns for most motion planes, discrepancies associated with limited sample sizes and different imaging techniques and/or spine configurations, were noted. Among healthy/asymptomatic individuals, flexion extension (FE) and lateral bending (LB) are mainly facilitated by the subaxial cervical spine. C4-C5 and C5-C6 were the major FE contributors in the reported studies, exceeding the motion contribution of sub-adjacent segments. Axial rotation (AR) greatly depends on C1-C2. FE range of motion (ROM) is distributed between the atlantoaxial and subaxial segments, while AR ROM stems mainly from the former and LB ROM from the latter. In coupled motion rotation is quantitatively predominant over translation. Motion migrates caudally from C1-C2 and the center of rotation (COR) translocates anteriorly and superiorly for each successive subaxial segment. In degenerative settings, concurrent or subsequent lesions render the association between diseases and mobility alterations challenging. The affected segments seem to maintain translational and angular motion in early and moderate degeneration. However, the progression of degeneration restrains mobility, which seems to be maintained or compensated by adjacent non-affected segments. While the kinematics of the healthy cervical spine have been addressed by multiple studies, the entire nosological and kinematic spectrum of cervical spine degeneration is partially addressed. Large-scale in vivo studies can complement the existing evidence, cover the gaps and pave the way to technological and clinical breakthroughs.
Topics: Humans; Biomechanical Phenomena; Cervical Vertebrae; Spinal Diseases; Rotation; Range of Motion, Articular
PubMed: 36496482
DOI: 10.1007/s10439-022-03088-8 -
Exercise Immunology Review 2022The complement system is comprised of the classical, lectin and alternative pathways that result in the formation of: pro-inflammatory anaphylatoxins; opsonins that...
BACKGROUND
The complement system is comprised of the classical, lectin and alternative pathways that result in the formation of: pro-inflammatory anaphylatoxins; opsonins that label cells for phagocytic removal; and, a membrane attack complex that directly lyses target cells. Complement-dependent cytotoxicity (CDC) - cell lysis triggered by complement protein C1q binding to the Fc region of antibodies bound to target cells - is another effector function of complement and a key mechanism-of-action of several monoclonal antibody therapies. At present, it is not well established how exercise affects complement system proteins in humans.
METHODS
A systematic search was conducted to identify studies that included original data and investigated the association between soluble complement proteins in the blood of healthy humans, and: 1) an acute bout of exercise; 2) exercise training interventions; or, 3) measurements of habitual physical activity and fitness.
RESULTS
77 studies were eligible for inclusion in this review, which included a total of 10,236 participants, and 40 complement proteins and constituent fragments. Higher levels of exercise training and cardiorespiratory fitness were commonly associated with reduced C3 in blood. Additionally, muscle strength was negatively associated with C1q. Elevated C3a-des-Arg, C4a-des-Arg and C5a, lower C1-inhibitor, and unchanged C3 and C4 were reported immediately post-laboratory based exercise, compared to baseline. Whereas, ultra-endurance running and resistance training increased markers of the alternative (factor B and H), classical (C1s), and leptin (mannose binding lectin) pathways, as well as C3 and C6 family proteins, up to 72-h following exercise. Heterogeneity among studies may be due to discrepancies in blood sampling/handling procedures, analytical techniques, exercise interventions/measurements and fitness of included populations.
CONCLUSIONS
Increased anaphylatoxins were observed immediately following an acute bout of exercise in a laboratory setting, whereas field-based exercise interventions of a longer duration (e.g. ultra-endurance running) or designed to elicit muscle damage (e.g. resistance training) increased complement proteins for up to 72-h. C3 in blood was mostly reduced by exercise training and associated with increased cardiorespiratory fitness, whereas C1q appeared to be negatively associated to muscle strength. Thus, both acute bouts of exercise and exercise training appear to modulate complement system proteins. Future research is needed to assess the clinical implications of these changes, for example on the efficacy of monoclonal antibody therapies dependent on CDC.
Topics: Anaphylatoxins; Antibodies, Monoclonal; Complement C1q; Complement System Proteins; Exercise; Humans
PubMed: 35452398
DOI: No ID Found -
Kidney International Jan 2015In this study, we conducted a systematic review of the literature to re-evaluate the role of C4d in the diagnosis of acute antibody-mediated rejection of kidney... (Review)
Review
In this study, we conducted a systematic review of the literature to re-evaluate the role of C4d in the diagnosis of acute antibody-mediated rejection of kidney allografts. Electronic databases were searched until September 2013. Eligible studies allowed derivation of diagnostic tables for the performance of C4d by immunofluorescence or immunohistochemistry with comparison to histopathological features of acute antibody-mediated rejection and/or donor-specific antibody (DSA) assays. Of 3492 unique abstracts, 29 studies encompassing 3485 indication and 868 surveillance biopsies were identified. Assessment of C4d by immunofluorescence and immunohistochemistry exhibited slight to moderate agreement with glomerulitis, peritubular capillaritis, solid-phase DSA assays, DSA with glomerulitis, and DSA with peritubular capillaritis. The sensitivity and specificity of C4d varied as a function of C4d and comparator test thresholds. Prognostically, the presence of C4d was associated with inferior allograft survival compared with DSA or histopathology alone. Thus, our findings support the presence of complement-dependent and -independent phenotypes of acute antibody-mediated rejection. Whether the presence of C4d in combination with histopathology or DSA should be considered for the diagnosis of acute antibody-mediated rejection warrants further study.
Topics: Acute Disease; Antibodies; Complement C4b; Fluorescent Antibody Technique; Graft Rejection; Humans; Immunohistochemistry; Kidney Transplantation; Peptide Fragments; Prognosis
PubMed: 24827778
DOI: 10.1038/ki.2014.166 -
Environmental Health Perspectives Dec 2002Animal studies indicate that the immune system is one of the most sensitive targets of the toxic effects of 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD). TCDD inhibits... (Comparative Study)
Comparative Study Review
Animal studies indicate that the immune system is one of the most sensitive targets of the toxic effects of 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD). TCDD inhibits immunoglobulin secretion and decreases resistance to bacterial, viral, and parasitic infections in exposed animals. Nearly 20 years after the Seveso, Italy, accident, we measured immunoglobulin and complement plasma levels in a random sample of the population in the most highly exposed zones (n = 62) and in the surrounding noncontaminated area (n = 58). Plasma IgG levels decreased with increasing TCDD plasma concentration (r = -0.35, p = 0.0002). Median IgG concentration decreased from 1,526 mg/dL in the group with the lowest (< 3.5 ppt) TCDD levels to 1,163 mg/dL in the group with the highest (20.1-89.9 ppt) TCDD levels (p = 0.002). The association was significant (p = 0.0004) after adjusting for age, sex, smoking, and consumption of domestic livestock and poultry in multiple regression analysis and persisted after exclusion of subjects with inflammatory diseases and those using antibiotics or nonsteroidal anti-inflammatory drugs. IgM, IgA, C3, and C4 plasma concentrations did not exhibit any consistent association with TCDD levels. We performed a systematic review of all the articles published between 1966 and 2001 on human subjects exposed to TCDD reporting information on circulating levels of immunoglobulins and/or complement components. The literature indicates that the evidence for effects of TCDD on humoral immunity is sparse. Methodologic issues, results, and possible sources of variation between studies are discussed. The possible long-term immunologic effects of TCDD exhibited by the participants of the present study, coupled with the increased incidence of lymphatic tumors in the area of the accident, warrant further investigation.
Topics: Accidents; Adult; Aged; Antibody Formation; Carcinogens; Child; Child, Preschool; Environmental Exposure; Female; Follow-Up Studies; Humans; Immunoglobulins; Italy; Lymphoma; Male; Middle Aged; Polychlorinated Dibenzodioxins; Public Health; Risk Assessment
PubMed: 12460794
DOI: 10.1289/ehp.021101169 -
Frontiers in Pharmacology 2023Chinese herbal medicine (CHM) was used to prevent and treat coronavirus disease 2019 (COVID-19) in clinical practices. Many studies have demonstrated that the...
Chinese herbal medicine (CHM) was used to prevent and treat coronavirus disease 2019 (COVID-19) in clinical practices. Many studies have demonstrated that the combination of CHM and Western medicine can be more effective in treating COVID-19 compared to Western medicine alone. However, evidence-based studies on the prevention in undiagnosed or suspected cases remain scarce. This systematic review and meta-analysis aimed to investigate the effectiveness of CHM in preventing recurrent, new, or suspected COVID-19 diseases. We conducted a comprehensive search using ten databases including articles published between December 2019 and September 2023. This search aimed to identify studies investigating the use of CHM to prevent COVID-19. Heterogeneity was assessed by a random-effects model. The relative risk (RR) and mean differences were calculated using 95% confidence intervals (CI). The modified Jadad Scale and the Newcastle-Ottawa Scale (NOS) were employed to evaluate the quality of randomized controlled trials and cohort studies, respectively. Seventeen studies with a total of 47,351 patients were included. Results revealed that CHM significantly reduced the incidence of COVID-19 (RR = 0.24, 95% CI = 0.11-0.53, = 0.0004), influenza (RR = 0.37, 95% CI = 0.18-0.76, = 0.007), and severe pneumonia exacerbation rate (RR = 0.17, 95% CI = 0.05-0.64, = 0.009) compared to non-treatment or conventional control group. Evidence evaluation indicated moderate quality evidence for COVID-19 incidence and serum complement components C3 and C4 in randomized controlled trials. For the incidence of influenza and severe pneumonia in RCTs as well as the ratio of CD4/CD8 lymphocytes, the evidence quality was low. The remaining outcomes including the disappearance rate of symptoms and adverse reactions were deemed to be of very low quality. CHM presents a promising therapeutic option for the prevention of COVID-19. However, additional high-quality clinical trials are needed to further strengthen evidential integrity.
PubMed: 38044944
DOI: 10.3389/fphar.2023.1257345