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Immunohematology Dec 2019This update of the Chido/Rodgers blood group system (Mougey R. A review of the Chido/Rodgers blood group. Immunohematology 2010;26:30-8) summarizes the current... (Review)
Review
This update of the Chido/Rodgers blood group system (Mougey R. A review of the Chido/Rodgers blood group. Immunohematology 2010;26:30-8) summarizes the current understanding of the genetics and serology of this blood group (of which little has changed since the publication of the first review) in a table format as well as summarizes the gene frequencies and disease association with low copy number of C4A or C4B genes. The International Society of Blood Transfusion (ISBT) has designated the ISBT number 017 to this system and the abbreviation CH/RG for the antigen or antibody notation. There are currently nine antigens in the CH/RG system. A brief discussion on the serologic challenges of detecting the antibodies and of newer information on the disease associations is provided. This review concludes with some speculation on how our understanding of C4 genes may be illuminated by current investigation into complexities of autoimmunity and the role of C4 and its progression to a disease state.
Topics: Antibodies; Blood Group Antigens; Complement C4; Complement C4b; Humans
PubMed: 31935328
DOI: No ID Found -
Sports Medicine - Open Jan 2024Although regular physical activity improves immune competency and reduces the prevalence of inflammatory diseases, strenuous training in elite athletes is associated...
BACKGROUND
Although regular physical activity improves immune competency and reduces the prevalence of inflammatory diseases, strenuous training in elite athletes is associated with an increased susceptibility to infectious complications. Therefore, the objective of our study was to assess the routinely examined parameters of the complement system in elite athletes. The study was carried out in a cohort of elite athletes (n = 134) and healthy control subjects (n = 110). In all subjects, besides a routine laboratory check-up, serum concentrations of the C3 and C4 complement components, mannose-binding lectin (MBL), as well as activation of all three complement pathways were determined.
RESULTS
Compared to healthy controls, lower C3 and C4 complement component concentrations were observed in elite athletes (0.96 ± 0.1 vs. 1.08 ± 0.2 mg/L, and 0.18 ± 0.1 vs. 0.25 ± 0.1 mg/L, respectively, p < 0.05); with much higher frequency rates of C3 and C4 deficiencies in athletes (31.3 vs. 14.5%, and 6 vs. 0%, p < 0.05). Simultaneously, athletes had much higher frequency rates of deficiencies of activation of classical and alternative complement pathways; while, deficiency of activation of the lectin pathway was similar in both cohorts.
CONCLUSIONS
We confirmed a high frequency of defects in the complement system in elite athletes. Lower concentrations of C3 and C4 complement components, with high frequencies of deficiencies of the classical and alternative complement activation pathways were the most prevalent disorder of the complement system in elite athletes. Further studies are needed to uncover the functional impacts of these observations upon the susceptibility to infectious diseases.
PubMed: 38252367
DOI: 10.1186/s40798-024-00681-0 -
Current Eye Research May 2022This study aims to explore the differences in the levels of complement components and complement regulatory factors in the vitreous humor of patients with retinal...
PURPOSE
This study aims to explore the differences in the levels of complement components and complement regulatory factors in the vitreous humor of patients with retinal detachment with choroidal detachment (RRDCD), patients with rhegmatogenous retinal detachment (RRD).
METHODS
A prospective case-control study design was used to recruit 20 patients with RRDCD and 20 patients with RRD in consecutive cases who underwent pars plana vitrectomy from March 2019 to January 2020. The control group comprised 15 patients with epiretinal membrane and 5 eyes from cadavers. The concentrations of complement C2, complement C4b, complement C5/C5a, complement C9, complement factor D (CFD), lectin, and complement factor I (CFI) were measured using Multiplex Luminex Assay, and the concentration of soluble decay acceleration factor (sDAF) was measured using ELISA.
RESULTS
As compared with the RRD and control groups, complement C2, complement C4b, complement C5/C5a, complement C9, CFD, lectin, CFI, and sDAF were significantly increased in the RRDCD group. Additionally, as compared with the control group, the concentrations of complement component C2 and CFD were significantly increased in the vitreous humor of the RRD group.
CONCLUSION
Components of all three complement pathways were elevated in eyes with RRDCD. Interestingly, while there was evidence of early complement activation in RRD, the final common pathway components were not elevated. In contrast, RRDCD eyes showed significant elevations of the MAC complex components, underscoring a potential pathophysiologic impact of complement activation in this condition.
Topics: Case-Control Studies; Choroidal Effusions; Complement C2; Complement C4b; Complement C5a; Humans; Lectins; Retinal Detachment; Retrospective Studies; Vitrectomy
PubMed: 35176953
DOI: 10.1080/02713683.2022.2038634 -
Viruses Jun 2023Adenovirus has strong therapeutic potential as an oncolytic virus and gene therapy vector. However, injecting human species C serotype 5 adenovirus, HAdv-C5, into the...
Adenovirus has strong therapeutic potential as an oncolytic virus and gene therapy vector. However, injecting human species C serotype 5 adenovirus, HAdv-C5, into the bloodstream leads to numerous interactions with plasma proteins that affect viral tropism and biodistribution, and can lead to potent immune responses and viral neutralization. The HAdv/factor X (FX) interaction facilitates highly efficient liver transduction and protects virus particles from complement-mediated neutralization after intravenous delivery. Ablating the FX interaction site on the HAdv-C5 capsid leaves the virus susceptible to neutralization by natural IgM followed by activation of the complement cascade and covalent binding of complement components C4b and C3b to the viral capsid. Here we present structural models for IgM and complement components C1, C4b, and C3b in complex with HAdv-C5. Molecular dynamics simulations indicate that when C3b binds near the vertex, multiple stabilizing interactions can be formed between C3b, penton base, and fiber. These interactions may stabilize the vertex region of the capsid and prevent release of the virally encoded membrane lytic factor, protein VI, which is packaged inside of the viral capsid, thus effectively neutralizing the virus. In a situation where FX and IgM are competing for binding to the capsid, IgM may not be able to form a bent conformation in which most of its Fab arms interact with the capsid. Our structural modeling of the competitive interaction of FX and IgM with HAdv-C5 allows us to propose a mechanistic model for FX inhibition of IgM-mediated virus neutralization. According to this model, although IgM may bind to the capsid, in the presence of FX it will likely retain a planar conformation and thus be unable to promote activation of the complement cascade at the virus surface.
Topics: Humans; Adenoviridae; Factor X; Tissue Distribution; Complement System Proteins; Adenoviruses, Human; Capsid Proteins; Immunoglobulin M; Models, Structural
PubMed: 37376642
DOI: 10.3390/v15061343 -
Thrombosis and Haemostasis Sep 2019High levels of complement C3 are associated with venous thrombosis (VT) in the general population. We investigated if high C3 and C4 levels were associated with...
High levels of complement C3 are associated with venous thrombosis (VT) in the general population. We investigated if high C3 and C4 levels were associated with pregnancy-related VT. We undertook the Norwegian VIP study, a case-control study of VT in pregnancy or within 3 months postpartum (cases, = 313) and women without pregnancy-related VT (controls, = 353). Determinants of C3 and C4 in the control women were investigated with linear regression and the odds ratio (OR) for pregnancy-related VT was calculated with logistic regression. We found that levels of C3 and C4 were associated with body mass index (BMI), C-reactive protein (CRP); with the coagulation factors (F) fibrinogen, FVIII, and FIX; and with the coagulation inhibitors antithrombin, protein C, protein S, and tissue factor pathway inhibitor. These associations were influenced by CRP levels. The crude OR for pregnancy-related VT was 1.8 (95% confidence interval [CI], 1.1-3.0) for C3 above the 90th percentile and 2.0 (95% CI, 1.2-3.2) for C4 above the 90th percentile. Stratification in antenatal and postnatal VT showed that C3 and C4 were only associated with postnatal VT with an OR for high C3 of 3.0 (95% CI, 1.8-5.0), and for high C4 of 2.6 (95% CI, 1.5-4.6). Adjustment for high FIX and BMI reduced the ORs. We conclude that the association between postnatal VT and C3 and C4 suggests that there is clinically relevant crosstalk between the complement and the coagulation system.
Topics: Adult; Blood Coagulation; Blood Coagulation Factors; Body Mass Index; C-Reactive Protein; Case-Control Studies; Complement C3; Complement C4; Female; Humans; Norway; Postpartum Period; Pregnancy; Pregnancy Complications; Venous Thrombosis
PubMed: 31254974
DOI: 10.1055/s-0039-1692426 -
Pediatric Research Jan 2020Complement promotes inflammatory and immune responses and may affect cardiometabolic risk. This study was designed to investigate the effect of complement components C3...
BACKGROUND
Complement promotes inflammatory and immune responses and may affect cardiometabolic risk. This study was designed to investigate the effect of complement components C3 and C4 on cardiometabolic risk in healthy non-Hispanic white adolescents.
METHODS
Body mass index (BMI), BMI percentile, waist circumference, and percent body fat were assessed in 75 adolescents. Arterial stiffness was assessed using arterial tomography and endothelial function using reactive hyperemia. Fasting lipids, inflammatory markers, and complement levels were measured and oral glucose tolerance test was performed. A single C3 polymorphism and C4 gene copy number variations were assessed.
RESULTS
C3 plasma levels increased with measures of obesity. Endothelial function worsened with increased C3 and C4 levels. Triglycerides and low-density lipoprotein increased and high-density lipoprotein (HDL) and insulin sensitivity decreased with increasing C3 levels, but the relationships were lost when body habitus was included in the model. C4 negatively related to HDL and positively to inflammatory markers. Subjects with at least one C3F allele had increased BMI and fat mass index. HDL was significantly related to C4L, C4S, C4A, and C4B gene copy number variation.
CONCLUSIONS
C3 levels increase with increasing body mass and increased C4 levels and copy number are associated with increased cardiometabolic risk in healthy adolescents.
Topics: Adiposity; Adolescent; Age Factors; Body Mass Index; Cardiometabolic Risk Factors; Child; Complement C3; Complement C4; Complement C4a; Complement C4b; Cross-Sectional Studies; DNA Copy Number Variations; Female; Gene Dosage; Humans; Male; Polymorphism, Single Nucleotide; Prospective Studies; Risk Assessment; Vascular Stiffness; Waist Circumference; White People
PubMed: 31404919
DOI: 10.1038/s41390-019-0534-1 -
Frontiers in Immunology 2022Neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody (MOG-IgG) associated disease (MOGAD) are autoimmune inflammatory... (Observational Study)
Observational Study
BACKGROUND AND OBJECTIVE
Neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody (MOG-IgG) associated disease (MOGAD) are autoimmune inflammatory demyelinating diseases of the central nervous system (CNS). As the clinical features of NMOSD are similar to MOGAD, diagnostic confusion exists between the two diseases. To better discriminate NMOSD from MOGAD, we investigated whether the plasma levels of complement 3 (C3) and complement 4 (C4) are different in NMOSD and MOGAD during the acute attacks of the diseases. We sought to determine whether C3 or C4 has an influence on the features of NMOSD.
METHODS
In this observational study, data from 73 aquaporin-4 antibodies (AQP4-IgG) positive NMOSD patients and 22 MOG-IgG positive MOGAD patients were collected retrospectively. Demographics, clinical characteristics, plasma parameters, and cerebrospinal fluid (CSF) findings will be analyzed for comparability between the two groups. Immunoglobulin-G (IgG) and albumin were measured in both plasma and CSF. Plasma levels of C3 and C4 were measured and compared between the NMOSD, MOGAD, and 42 healthy controls (HC). The correlations between plasma C3, C4, and NMOSD clinical parameters were analyzed.
RESULTS
The ages of onset were later in the AQP4-IgG positive NMOSD group and females predominated, which differed from the MOGAD group, whose ages were younger and with a slight male preponderance. The AQP4-IgG positive NMOSD patients presented with the clinical symptoms of optic neuritis (ON) and transverse myelitis (TM), whereas encephalitis symptoms were more prevalent in MOGAD patients. CSF analysis shows that slight but not significantly higher white cell count (WCC) and protein were observed in the MOGAD group than in the AQP4-IgG positive NMOSD group. The plasma levels of IgG in MOGAD patients are significantly lower ( = 0.027) than in NMOSD patients. On the contrary, the plasma levels of albumin in MOGAD were higher than in NMOSD, which reached statistical significance ( = 0.039). Both the plasma C3 and C4 levels in the NMOSD group were significantly lower than in MOGAD and HC. The receiver operating characteristic (ROC) curve of the prediction model comprises C3 and C4 to distinguish NMOSD from MOGAD [area under the curve (AUC): 0.731, 0.645], which are considered to have discriminatory values. The results of Spearman's analysis revealed that there was a significant positive correlation between the plasma C3 and the CSF WCC (r = 0.383, = 0.040). There was an inverse correlation between plasma C4 and plasma IgG (r = -0.244, = 0.038). Plasma C3 or C4 was significantly positively correlated with CSF albumin and Q-Alb, which is considered a measure of blood-brain barrier (BBB) disruption.
CONCLUSION
During the acute phase of NMOSD and MOGAD, plasma C3 and C4 may become potential biomarkers for distinguishing the two diseases and reflecting the NMOSD BBB damage.
Topics: Albumins; Aquaporin 4; Biomarkers; Blood-Brain Barrier; Cell Movement; Complement C3; Complement C4; Female; Humans; Immunoglobulin G; Male; Myelin-Oligodendrocyte Glycoprotein; Neuromyelitis Optica; Retrospective Studies
PubMed: 35898513
DOI: 10.3389/fimmu.2022.853891 -
World Journal of Clinical Cases Dec 2022Hypersplenism associated with cirrhotic portal hypertension is a common condition often resulting from hepatitis B-related cirrhosis. However, the levels of...
BACKGROUND
Hypersplenism associated with cirrhotic portal hypertension is a common condition often resulting from hepatitis B-related cirrhosis. However, the levels of immunoglobulin (Ig) and complement in patients with hypersplenism associated with cirrhotic portal hypertension remain unclear. This study was undertaken to determine the levels of Ig and complement in these patients, the relationship between these levels and Child-Pugh class and their clinical significance.
AIM
To investigate the antibody (Ig) and complement levels in patients with hypersplenism associated with cirrhotic portal hypertension and their clinical significance.
METHODS
Clinical data of 119 patients with hypersplenism associated with cirrhotic portal hypertension were statistically analyzed and compared with those of 128 control patients.
RESULTS
IgA and IgG levels in patients with hypersplenism were significantly higher than controls ( < 0.001). There was no significant difference in IgM between the two groups ( = 0.109). C3 and C4 levels in patients with hypersplenism were significantly lower than controls ( < 0.001). As liver function decreased, IgA and IgG levels increased ( < 0.001), and C3 and C4 levels decreased ( < 0.001).
CONCLUSION
Patients with hypersplenism associated with cirrhotic portal hypertension have significantly higher antibody (IgA and IgG) levels and significantly lower complement (C3 and C4) levels, which are both related to liver damage. Clinically, the administration of anti-hepatitis virus agents and protection of liver function should be strengthened.
PubMed: 36683645
DOI: 10.12998/wjcc.v10.i36.13208 -
Methods in Molecular Biology (Clifton,... 2021Immunofluorescence staining of tissues has become a reliable and informative technique used in a diverse set of applications, ranging from simple detection of an antigen...
Immunofluorescence staining of tissues has become a reliable and informative technique used in a diverse set of applications, ranging from simple detection of an antigen of interest in a specific location to the semiquantitative analysis of spatial relationships between multiple antigens and/or cell types. During complement activation, circulating complement proteins are covalently fixed to target tissues, providing a durable marker of complement activation in the tissue, and many of these proteins can be readily detected by immunofluorescence microscopy. In general, staining for complement fragments is much like staining for other noncomplement epitopes. However, one key difference is the diligence with which unfixed tissues must be handled when staining for complement fragment. Here we explain the process of dual staining frozen mouse kidney sections for the complement proteins C3 and C4. Throughout the protocol, we will emphasize important steps for preserving complement protein integrity as well as tips to improve the signal-to-noise ratio to improve overall image quality.
Topics: Animals; Complement C3; Complement C4; Complement System Proteins; Fluorescent Antibody Technique; Formaldehyde; Frozen Sections; Kidney; Mice; Paraffin Embedding; Rats; Staining and Labeling
PubMed: 33847942
DOI: 10.1007/978-1-0716-1016-9_17 -
Frontiers in Psychiatry 2022To investigate the changes in immunity and clinical infection events among patients with chronic insomnia.
PURPOSE
To investigate the changes in immunity and clinical infection events among patients with chronic insomnia.
MATERIALS AND METHODS
Forty-two patients with chronic insomnia (age = 64.44 ± 10.53) and 47 normal controls (age = 67.08 ± 7.822) were selected to determine differences in data, such as complete blood counts (CBCs), biochemical indices, lymphocyte subsets, immunoglobulin (Ig), complement C3 and C4 and interleukin-6 (IL-6), as well as to compare the incidence of clinical infection between the two groups.
RESULTS
There were significant differences in erythrocyte, hemoglobin, hematocrit, albumin, globulin, creatinine, IgG, IgG/IgM ratio, CD4 T-lymphocytes, CD19-lymphocytes, CD4/CD8 ratio, platelet/lymphocyte ratio, CD19/CD3 ratio, and clinical infection events between the chronic insomnia group and the control group ( < 0.05). There was no significant difference in neutrophil, lymphocyte, monocyte, and platelet counts; lymphocyte subsets CD8 T and CD56; platelet-to-lymphocyte ratio (PLR); neutrophil-to-lymphocyte ratio (NLR); complement C3; complement C4; IgM; IgA; and IL-6 between the experimental group and their controls ( > 0.05). The systolic and diastolic blood pressures of the chronic insomnia group did not vary widely from those of the controls ( > 0.05).
CONCLUSION
Patients with chronic insomnia have immunological abnormalities, characterized by a higher incidence of clinical infection.
PubMed: 36329922
DOI: 10.3389/fpsyt.2022.1034405