ABSTRACT
OBJECTIVE: The complement system has been associated with the etiopathogenesis of rheumatoid arthritis (RA). Insulin resistance (IR) and metabolic syndrome (MetS) are prevalent among patients with RA. The aim of this study was to explore the relationship between a comprehensive evaluation of the complement system and IR, as well as MetS, in patients with RA. METHODS: A total of 339 nondiabetic patients with RA were recruited. Functional assays of the 3 complement pathways were assessed. Additionally, serum levels of the following individual components of the complement system were measured: C1q (classical); lectin (lectin); C2, C4, and C4b (classical lectin); factor D and properdin (alternative); C3 and C3a (common); C5, C5a, and C9 (terminal); as well as the factor I and C1 inhibitor regulators. IR and ß cell function indices were calculated using the homeostatic model assessment. Criteria for MetS were applied. Multivariable linear regression analysis was performed to investigate the association between the complement system and IR in patients with RA. RESULTS: Many elements of the upstream and common complement pathways, but not the functional tests of the 3 routes, correlated positively with higher levels of IR and ß cell function. However, after multivariable adjustment for factors associated with IR, these relationships were lost. Conversely, the presence of MetS in patients with RA maintained a relationship with higher levels of C1q, C4, C3, properdin, and factor I after adjusting for confounders. CONCLUSION: There is a positive correlation between the complement system and MetS among nondiabetic patients with RA. This association is independent of traditional IR factors.
ABSTRACT
The complement (C) system is implicated in the etiopathogenesis of rheumatoid arthritis (RA). However, there is a lack of studies characterizing all three C pathways in RA patients. This study aimed to evaluate the association between an in-depth examination of the C system and RA patient characteristics, focusing on disease activity and the presence of rheumatoid factor and anti-citrullinated protein autoantibodies (ACPA). In a cohort of 430 RA patients, functional assays of the three C pathways (classical, alternative, and lectin) and serum levels of their components were assessed. Components included C1q (classical); factor D and properdin (alternative); lectin (lectin); C1-inhibitor; C2, C4, and C4b (classical and lectin); C3, C3a, and C4b (common); and C5, C5a, and C9 (terminal). A multivariable linear regression analysis showed significant positive correlations between C-reactive protein and C system proteins and functional assays, especially in the terminal and common pathways. Disease activity, measured by scores with or without acute phase reactants, positively correlated with the classical pathway functional test and terminal pathway products. Conversely, rheumatoid factor or ACPA presence was associated with lower classical pathway values and decreased C3a and C4b levels, suggesting complement depletion. In conclusion, RA disease activity increases C molecules and functional complement assays, while rheumatoid factor or ACPA positivity is linked to C consumption. Our study offers a detailed analysis of the complement system's role in RA, potentially guiding the development of more targeted and effective treatment strategies.
Subject(s)
Arthritis, Rheumatoid , Rheumatoid Factor , Humans , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/metabolism , Male , Female , Middle Aged , Aged , Rheumatoid Factor/blood , Adult , Complement System Proteins/metabolism , Complement System Proteins/immunology , Anti-Citrullinated Protein Antibodies/blood , Complement Pathway, Alternative , Complement Activation , C-Reactive Protein/metabolism , C-Reactive Protein/analysis , Complement Pathway, ClassicalABSTRACT
BACKGROUND: Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular (CV) events and CV mortality. Subclinical carotid atherosclerosis is independently associated with rates of incident CV events among patients with RA. The complement system has been related to both the etiopathogenesis of RA and CV disease. In this study, we aimed to evaluate the association between a comprehensive assessment of the complement system and carotid intima media thickness and carotid plaque in patients with RA. METHODS: 430 patients with RA were recruited. Functional assays of the three pathways of the complement system, utilizing new-generation techniques, were assessed. Additionally, serum levels of individual components of the complement system belonging to the three pathways were measured: C1q (classical), lectin (lectin), C2, C4, and C4b (classical and lectin), factor D and properdin (alternative), C3 and C3a (common), C5, C5a, and C9 (terminal), as well as regulators factor I and C1-inhibitor. Subclinical carotid atherosclerosis was evaluated by ultrasonography. Multivariable linear regression analysis was conducted to investigate the association between the complement system and carotid intima media thickness and carotid plaque. RESULTS: After multivariable adjustment, which included traditional CV risk factors and disease-related data, C3a and C5a exhibited significant positive correlations with carotid intima media thickness. Additionally, higher values of C1-inhibitor, properdin, C3, C5, and C5a were independently associated with the presence of carotid plaque. CONCLUSION: The complement system and subclinical carotid atherosclerosis are linked in patients with RA.
Subject(s)
Arthritis, Rheumatoid , Carotid Artery Diseases , Carotid Intima-Media Thickness , Humans , Male , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/complications , Female , Carotid Artery Diseases/blood , Carotid Artery Diseases/epidemiology , Carotid Artery Diseases/diagnostic imaging , Middle Aged , Aged , Complement System Proteins/metabolism , Complement System Proteins/analysis , Adult , Cross-Sectional StudiesABSTRACT
Background: The complement system has been linked to the etiopathogenesis of rheumatoid arthritis (RA). Patients with RA exhibit a dysregulated profile of lipid molecules, which has been attributed to the inflammation present in the disease. In this study, we aimed to evaluate the association between a comprehensive assessment of the complement system and the lipid profile of patients with RA. Methods: 430 patients with RA were recruited. New-generation techniques were employed to conduct functional assays of the three pathways of the complement system. Serum levels of various complement components such as C1q, factor D, properdin, lectin, C1-inhibitor, C2, C4, C4b, C3, C3a, C5, C5a, and C9 were assessed. Furthermore, a complete pattern of lipid molecules was measured including high (HDL), low-density lipoproteins (LDL), and lipoprotein (a). Multivariable linear regression analysis was conducted to investigate the association between the complement system and lipid profile in RA patients. Results: After multivariable analysis, several noteworthy associations emerged between the complement system and lipid molecules. Notably, complement components most strongly linked to the lipid profile were C1q and properdin, representing the upstream classical and alternative pathways, along with C3 from the common cascade. These associations demonstrated significance and positivity concerning total cholesterol, LDL, atherogenic index, apolipoprotein B, and lipoprotein(a), suggesting a connection with an unfavorable lipid profile. Interestingly, complement functional assays of the three pathways and activated products such as C3a and C5a showed no correlation with the lipid pattern. Conclusion: The correlation between the complement system and lipid molecule patterns is pronounced in patients with RA. This relationship is predominantly positive and primarily associated with upstream complement components rather than activated ones.
Subject(s)
Arthritis, Rheumatoid , Complement System Proteins , Lipids , Humans , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/immunology , Female , Male , Middle Aged , Lipids/blood , Complement System Proteins/metabolism , Complement System Proteins/immunology , Adult , Aged , Complement Activation , Biomarkers/blood , Complement C1q/metabolism , Complement C1q/immunologyABSTRACT
No disponible
Subject(s)
Humans , Female , Middle Aged , Biotin/administration & dosage , Biotin/metabolism , Demyelinating Diseases/diet therapy , Dietary Supplements , Thyrotropin/analysis , Thyroxine/analysis , Dose-Response Relationship, Drug , Biomarkers, TumorSubject(s)
Biotin/administration & dosage , Diagnostic Errors , Hyperthyroidism/diagnosis , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Autoantibodies/blood , Autoantigens/immunology , Biotin/physiology , Female , Hashimoto Disease/blood , Hashimoto Disease/diagnosis , Hashimoto Disease/drug therapy , Humans , Hyperthyroidism/blood , Iodide Peroxidase/immunology , Iron-Binding Proteins/immunology , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/blood , Receptors, Thyrotropin/immunology , Streptavidin/metabolism , Thyroid Function Tests , Thyroiditis, Autoimmune/blood , Thyroiditis, Autoimmune/diagnosis , Thyroiditis, Autoimmune/drug therapy , Thyrotropin/blood , Thyroxine/bloodABSTRACT
OBJETIVOS: Analizar y comparar la capacidad de la procalcitonina (PCT), proteína C reactiva (PCR) y leucocitos para diferenciar la bacteriemia verdadera de los hemocultivos (HC) contaminados en los pacientes atendidos en el servicio de urgencias (SU) por un episodio de infección. MÉTODOS: Estudio observacional, retrospectivo y analítico de todos los HC con crecimiento positivo extraídos en un SU en los pacientes adultos (≥ 18 años) durante los años 2016 y 2017. Se realizó seguimiento durante 30 días y se calculó el poder y rendimiento pronóstico de bacteriemia verdadera. RESULTADOS: Se incluyeron 266 casos de HC con crecimiento positivo. De ellos se consideraron como bacteriemias verdaderas 154 (57,9%) y como HC contaminantes 112 (42,1%). Para la predicción de bacteriemia verdadera la PCT obtiene un área bajo la curva Receiver Operating Characteristic (ABC-ROC) de 0,983 (IC 95%: 0,972-0,994; p < 0,001) y con un punto de corte de PCT ≥ 0,43 ng/ml se consigue una sensibilidad del 94%, una especificidad del 91%, un valor predictivo positivo de 94% y un valor predictivo negativo de 92%. El ABC-ROC obtenida para la PCR fue de 0,639 (IC 95%: 0,572-0,707; p < 0,001), para el recuento de leucocitos de 0,693 (IC 95%: 0,630-0,756; p < 0,001) y para las formas inmaduras (> 10% cayados) de 0,614 (IC 95%: 0,547-0,682; p = 0,001). Los valores medios al comparar la PCT en las bacteriemias verdaderas y los HC contaminados fueron de 3,44 ng/ml (DE 6,30) frente a 0,16ng/ml (DE 0,18), p < 0,001. CONCLUSIONES: En los HC con crecimiento positivo extraídos en el SU la PCT consigue el mejor rendimiento pronóstico de bacteriemia verdadera diferenciándola de los HC contaminados, mayor que la PCR y los leucocitos
OBJECTIVES: To analyse and compare the ability of procalcitonin (PCT), C-reactive protein (CRP) and leukocytes to differentiate true bacteraemia from contaminated blood cultures in patients seen in the emergency department (ED) for an episode of infectious disease. METHODS: Observational, retrospective and descriptive analytical study of all blood cultures with positive growth extracted in an ED in adult patients (≥ 18 years) during 2016 and 2017. The follow-up was carried out over a 30-day period to calculate the predictive power and the prognostic performance for true bacteraemia. RESULTS: A total of 266 blood cultures with positive growth were included in the study. Out of these, 154 (57.9%) were considered true bacteraemia and 112 (42.1%) were considered to be contaminated blood cultures. The area under the Receiver Operating Characteristic curve (AUC-ROC) for PCT to predict true bacteraemia was 0.983 (95% CI: 0.972-0.994; P < 0.001) and, considering a cut-off value of ≥ 0.43 ng/ml, PCT achieved 94% sensitivity, 91% specificity, positive predictive value of 94%, and negative predictive value of 92%. The AUC-ROC obtained for CRP was 0.639 (95% CI: 0.572-0.707, P < .001), for leukocytes of 0.693 (95% CI: 0.630-0.756, P < .001) and for immature leukocytes (> 10% bands) of 0.614 (95% CI: 0.547-0.682, P < .001). The mean values for PCT were 3.44 (SD 6.30) ng/ml in true bacteraemia vs. 0.16 (SD 0.18) ng/ml in contaminated blood cultures (P < .001). CONCLUSIONS: In blood cultures with positive growth extracted in an ED, PCT achieves the best prognostic performance of true bacteraemia vs. contaminated blood cultures, better than CRP and leukocytes
Subject(s)
Humans , Procalcitonin/analysis , Bacteremia/diagnosis , Biomarkers/analysis , Emergency Medical Services , Predictive Value of Tests , Blood/microbiology , Bacteremia/pathology , C-Reactive Protein/analysis , Retrospective Studies , Blood CultureABSTRACT
OBJECTIVES: To analyse and compare the ability of procalcitonin (PCT), C-reactive protein (CRP) and leukocytes to differentiate true bacteraemia from contaminated blood cultures in patients seen in the emergency department (ED) for an episode of infectious disease. METHODS: Observational, retrospective and descriptive analytical study of all blood cultures with positive growth extracted in an ED in adult patients (≥18 years) during 2016 and 2017. The follow-up was carried out over a 30-day period to calculate the predictive power and the prognostic performance for true bacteraemia. RESULTS: A total of 266 blood cultures with positive growth were included in the study. Out of these, 154 (57.9%) were considered true bacteraemia and 112 (42.1%) were considered to be contaminated blood cultures. The area under the Receiver Operating Characteristic curve (AUC-ROC) for PCT to predict true bacteraemia was 0.983 (95% CI: 0.972-0.994; P<0.001) and, considering a cut-off value of≥0.43 ng/ml, PCT achieved 94% sensitivity, 91% specificity, positive predictive value of 94%, and negative predictive value of 92%. The AUC-ROC obtained for CRP was 0.639 (95% CI: 0.572-0.707, P<.001), for leukocytes of 0.693 (95% CI: 0.630-0.756, P<.001) and for immature leukocytes (>10% bands) of 0.614 (95% CI: 0.547-0.682, P<.001). The mean values for PCT were 3.44 (SD 6.30) ng/ml in true bacteraemia vs. 0.16 (SD 0.18) ng/ml in contaminated blood cultures (P<.001). CONCLUSIONS: In blood cultures with positive growth extracted in an ED, PCT achieves the best prognostic performance of true bacteraemia vs. contaminated blood cultures, better than CRP and leukocytes.