-
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 -
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 -
Journal of Autoimmunity Apr 2023Finkelstein-Seidlmayer vasculitis, also called acute hemorrhagic edema of young children or infantile immunoglobulin A vasculitis, is habitually a benign skin-limited...
Finkelstein-Seidlmayer vasculitis, also called acute hemorrhagic edema of young children or infantile immunoglobulin A vasculitis, is habitually a benign skin-limited small vessel leukocytoclastic vasculitis that mainly affects infants 24 months or less of age. Since this disease is commonly triggered by an infection, an immune-mediated origin has been postulated. To better appreciate the possible underlying immune mechanism of this vasculitis, we addressed circulating autoimmune markers and vascular immune deposits in patients contained in the Acute Hemorrhagic Edema BIbliographic Database, which incorporates all original reports on Finkelstein-Seidlmayer vasculitis. A test for at least one circulating autoimmune marker or a vascular immune deposit was performed in 243 cases. Subunits of complement system C4 resulted pathologically reduced in 4.7% and C3 in 1.4%, rheumatoid factor was detected in 6.1%, and antinuclear antibodies in 1.9% of cases. Antineutrophil cytoplasmic antibodies were never demonstrated. Immunofluorescence studies were performed on 125 skin biopsy specimens and resulted positive for complement subunits in 46%, fibrinogen in 45%, immunoglobulin A in 25%, immunoglobulin M in 24%, immunoglobulin G in 13%, and immunoglobulin E in 4.2% of cases. Infants testing positive for vascular immunoglobulin A deposits did not present a higher prevalence of systemic involvement or recurrences, nor a longer disease duration. In conclusion, we detected a very low prevalence of circulating autoimmune marker positivity in Finkelstein-Seidlmayer patients. Available immunofluorescence data support the notion that immune factors play a relevant role in this vasculitis. Furthermore, vascular immunoglobulin A deposits seem not to play a crucial role in this disease.
Topics: Child; Infant; Humans; Child, Preschool; Vasculitis; Vasculitis, Leukocytoclastic, Cutaneous; Immunoglobulin A; Immunoglobulin G; Hemorrhage; Edema
PubMed: 36822150
DOI: 10.1016/j.jaut.2023.103002 -
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 Pharmacology 2022Total glucosides of paeony (TGP), extracted from the Chinese medicine Pall., have been proven to be effective in various autoimmune diseases. We aim to systematically...
Total glucosides of paeony (TGP), extracted from the Chinese medicine Pall., have been proven to be effective in various autoimmune diseases. We aim to systematically evaluate the efficacy and safety of TGP combined with different conventional therapeutic agents in the treatment of systemic lupus erythematosus (SLE). Eight databases were searched for randomized controlled studies of TGP for SLE. The search time was set from the establishment of the databases to March 2022. The risk of bias was assessed by the Cochrane Evaluation Manual (5.1.0), RevMan 5.3 software was used for meta-analysis, and the certainty of the evidence was assessed by the GRADE methodology. A total of 23 articles were included, including 792 patients overall in the treatment group and 781 patients overall in the control group. The meta-analysis results showed that TGP combined with conventional treatments was superior to the conventional treatments in reducing the SLE disease activity and the incidence of adverse reactions (SMD = -1.98, 95% Cl = [-2.50, -1.46], < 0.001; SMD = -0.65, 95% Cl = [-1.04, -0.26], <0.001; SMD = -0.94, 95% Cl = [-1.53, -0.34], < 0.05; SMD = -1.00, 95% Cl = [-1.64, -0.36], < 0.05; and RR = 0.37, 95% Cl = [0.21, 0.64], < 0.001). The results also showed that TGP helped improve other outcomes related to SLE disease activity, such as complement proteins (C3 and C4), immunoglobulins (IgA, IgM and, IgG), ESR, CRP, 24 h urine protein, and recurrence rate. In addition, TGP may also be effective in reducing the average daily dosage of glucocorticoids (GCs) and the cumulative dosage of cyclophosphamide (CTX). The certainty of the evidence was assessed as moderate to low. TGP is more effective and safer when used in combination with different conventional therapeutic agents. It helped reduce the disease activity of SLE and the incidence of adverse reactions. However, we should be cautious about these conclusions as the quality of the evidence is poor. Future studies should focus on improving the methodology. High-quality randomized controlled trials (RCTs) will be necessary to provide strong evidence for the efficacy of TGP for SLE. https://www.crd.york.ac.uk/PROSPERO, identifier CRD42021272481.
PubMed: 36569311
DOI: 10.3389/fphar.2022.932874 -
Medicine Dec 2022To evaluate the efficacy and safety of total glucosides of paeony in the treatment of systemic lupus erythematosus (SLE). (Meta-Analysis)
Meta-Analysis
BACKGROUND
To evaluate the efficacy and safety of total glucosides of paeony in the treatment of systemic lupus erythematosus (SLE).
METHODS
From the creation of the database to July 2021, multiple databases were searched for randomized controlled trials of treating SLE with total glucosides of paeony (TGP) combining chemical medicine. After screening, quality evaluation and data extraction, the included studies were analyzed by Revman5.3 software.
RESULTS
A total of 11 studies were included, including 836 patients (treatment group 417, control group 419). Meta analysis showed that on the basis of routine treatment, TGP could further improve the treatment effective rate (OR = 4.19, 95% CI: 2.21 to 7.95, Z = 4.38, P < .0001), reduced SLE Disease Activity Index (SLEDAI) (MD = -1.70, 95%CI: -2.51 to -0.89, Z = 4.11, P < .0001) and erythrocyte sedimentation rate (MD = -7.04, 95%CI: -8.48 to -5.59, Z = 9.53, P < .00001), reduced the level of immunoglobulin A (IgA) (MD = -0.60, 95%CI: -0.82 to -0.37, Z = 5.24, P < .00001), immunoglobulin G (IgG) (MD = -2.97, 95%CI: -3.72 to -2.23, Z = 7.82, P < .00001), and immunoglobulin M (IgM) (MD = -0.36, 95%CI: -0.45 to -0.27, Z = 7.54, P < .00001), increased the level of complement C3 (MD = 0.34, 95%CI: 0.30 to 0.39, Z = 14.40, P < .00001) and complement C4 (MD = 0.07, 95%CI: 0.06 to 0.08, Z = 10.08, P < .00001), and decreased the recurrence (OR = 0.31, 95%CI: 0.16 to 0.61, Z = 3.39, P = .0007), and there was no significant difference in the incidence of adverse reactions (OR = 0.93, 95%CI: 0.45 to 1.91, Z = 0.20, P = .84).
CONCLUSION
On the basis of conventional treatment, the combined use of TGP can enhance the clinical efficacy of SLE without increasing the incidence of adverse effects.
Topics: Humans; Glucosides; Paeonia; Lupus Erythematosus, Systemic; Treatment Outcome
PubMed: 36550839
DOI: 10.1097/MD.0000000000032029 -
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 -
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 -
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 -
Frontiers in Pharmacology 2022Total glucosides of paeony (TGP), extracted from the dried roots of Pall., are proven to regulate immune function in various rheumatic diseases. We aim to... (Review)
Review
Total glucosides of paeony (TGP), extracted from the dried roots of Pall., are proven to regulate immune function in various rheumatic diseases. We aim to systematically evaluate the efficacy and safety of TGP in reducing disease activity in systemic lupus erythematosus (SLE). We searched trials in seven electronic databases and two clinical trail registries. Randomized controlled trials (RCTs) evaluating efficacy and safety of TGP for SLE were identified. The Cochrane Risk of Bias Tool 2.0 was used for quality assessment of the included trials, and RevMan 5.4 software was used for meta-analysis. A total of 14 RCTs were included, including 978 participants, 492 in the intervention group and 486 in the control group. Regarding the efficacy of TGP for SLE, results showed that TGP plus conventional treatments (CTs) was superior to CTs alone in reducing disease activity ( = -3.54, 95% = -4.08 to -3.00, < 0.00001; = -3.80, 95% = -4.51 to -3.09, < 0.00001; = -1.62, 95% = -2.60 to -0.64, < 0.0001; = -1.97, 95% = -3.18 to -0.76, = 0.001). The results also showed that TGP contributed to a betterment in improving other outcomes related to lupus activity, such as ESR, CRP, complement proteins (C3, C4), and immunoglobulins (IgA, IgM). In addition, TGP significantly decreased average daily glucocorticoid dosage and cumulative cyclophosamide dosage, as well as disease recurrence rate. In terms of safety, TGP may reduce the incidence of adverse reactions ( = 0.51, 95% = 0.29 to 0.88, = 0.01). The certainty of the evidence were assessed as moderate to low. TGP appears potentially effective and generally safe in reducing disease activity in SLE. However, in view of high risk of bias, the findings need to be confirmed in high-quality trials. : https://www.crd.york.ac.uk/prospero, identifier CRD42021274850.
PubMed: 35173622
DOI: 10.3389/fphar.2022.834947