RESUMO
Chronic inflammation is believed as the main culprit of the link between cardiovascular disease (CVD) and rheumatoid arthritis (RA). Interleukin-6 (IL-6) is a pro-inflammatory cytokine with a key role in RA pathophysiology and also correlates with joint destruction and disease activity. This study evaluates the association between IL-6 plasma level and cardiac biomarker NT-proBNP, HS-CRP, CVD predictor algorithms, Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE), as well as with CXCL9 and its receptor, CXCR3 in RA patients compared to the controls. Sixty RA patients (30 early and 30 late) and 30 healthy persons were included in this study. IL-6 and NT-proBNP plasma levels were measured by the ELISA. Also, HS-CRP plasma levels were quantified using the immunoturbidimetric assay. The CVD risk was assessed by the FRS and SCORE. IL-6 plasma levels were significantly higher in the early and late RA patients compared to the controls (p < 0.001). There was a positive correlation between IL-6 with DAS-28 (p = 0.007, r = 0.346), BPS (p = 0.002, r = 0.396), BPD (p = 0.046, r = 0.259), SCORE (p < 0.001, r = 0.472), and FRS (p < 0.001, r = 0.553), and a negative association with HDL (p = 0.037, r = -0.270), in the patients. Also, IL-6 plasma level positively correlated with HS-CRP (p = 0.021, r = 0.297) and NT-proBNP (p = 0.045, r = 0.260) in the patients. Furthermore, a positive association was found between IL-6 plasma levels and CXCL9 (p = 0.002, r = 0.386), and CXCR3 (p = 0.018, r = 0.304) in the patients. Given the interesting association between IL-6 with various variables of CVD, IL-6 may be considered a biomarker for assessing the risk for future cardiovascular events in RA patients.
Assuntos
Algoritmos , Artrite Reumatoide , Biomarcadores , Proteína C-Reativa , Doenças Cardiovasculares , Interleucina-6 , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Humanos , Artrite Reumatoide/sangue , Artrite Reumatoide/complicações , Biomarcadores/sangue , Feminino , Masculino , Interleucina-6/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Proteína C-Reativa/metabolismo , Fragmentos de Peptídeos/sangue , Quimiocina CXCL9/sangue , Adulto , Estudos de Casos e Controles , Idoso , Fatores de Risco , Receptores CXCR3RESUMO
OBJECTIVES: The dysregulated immune response is one of the cardinal features of severe coronavirus disease 2019 (COVID-19). This study was conducted to clarify the occurrence of autoantibodies (AABs) associated with systemic autoimmune rheumatic diseases (SARDs) in hospitalized patients with a moderate, severe, and critical form of COVID-19. METHODS: The serum samples obtained from 176 hospitalized COVID-19 patients were investigated in this study, including patients with moderate (N = 90), severe (N = 50), and critical (N = 36) forms of COVID-19. Also, the serum samples collected from healthy subjects before the COVID-19 pandemic were used as controls (N = 176). The antinuclear antibodies (ANAs), antidouble-stranded DNA (anti-dsDNA), cytoplasmic-anti neutrophil cytoplasmic antibody (c-ANCA), perinuclear ANCA (p-ANCA), antiphospholipid antibodies (aPLs), and anticyclic citrullinated peptide (anti-CCP) occurrence was evaluated using a solid-phase enzyme-linked immunosorbent assay (ELISA). RESULTS: The results showed that the occurrence of ANAs, anti-dsDNA, anti-CCP, c-ANCA, and p-ANCA was significantly higher in the COVID-19 patients compared to serum obtained from healthy subjects (p < .0001, p < .0001, p < .0001, p < .05, and p < .001, respectively). The positive number of anti-CCP tests increased significantly in severe COVID-19 compared to the moderate group (p < .01). CONCLUSION: Our study further supports the development of autoantibodies related to systemic autoimmune rheumatologic diseases. To the best of our knowledge, this is the first study with a large sample size that reported the occurrence of anti-CCP in a severe form of COVID-19.
Assuntos
Anticorpos Antiproteína Citrulinada , COVID-19 , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Antiproteína Citrulinada/sangue , Anticorpos Antiproteína Citrulinada/imunologia , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/sangue , COVID-19/imunologia , COVID-19/sangue , Doenças Reumáticas/imunologia , Doenças Reumáticas/sangue , SARS-CoV-2/imunologia , Índice de Gravidade de DoençaRESUMO
INTRODUCTION: Cardiovascular disease (CVD) is the most critical extra-articular manifestation of rheumatoid arthritis, and inflammatory molecules contribute to its pathogenesis. Recently, CXCL9 has been considered an inflammatory chemokine associated with the pathogenesis of CVD. Here, we evaluated the association of plasma CXCL9 with well-established cardiac biomarkers, including HS-CRP (High sensitivity C-reactive protein) and NT-ProBNP (N-terminal pro-B-type natriuretic peptide), in newly diagnosed and under-treatment RA patients. METHODS: Thirty newly diagnosed patients, 30 under-treatment RA patients, and 30 healthy subjects were recruited. The plasma concentration of CXCL9 and NT-ProBNP was measured using the ELISA method. The HS-CRP levels was measured in plasma samples using latex-enhanced immunoturbidimetric test. RESULTS: We found increased plasma levels of CXCL9, HS-CRP, and NT-proBNP in RA patients compared to healthy subjects, besides that the concentration of CXCL9, HS-CRP, and NT-ProBNP showed elevated levels in newly diagnosed RA patients compared to under-treatment group. The mean plasma concentration of CXCL9, NT-proBNP, and HS-CRP were statistically different among healthy subjects, newly diagnosed, and under-treatment RA patients (p < 0.001, p = 0.016, and p < 0.001, respectively). We also found a significant positive correlation between CXCL9 and DAS-28 (p = 0.0005, r = 0.436) in the patients' group (new-case + under-treatment). There was a significantly positive correlation between CXCL9 and NT-proBNP in newly diagnosed and under-treatment patients (p = 0.020, r = 0.424; p < 0.0001, r = 0.853, respectively). In the patient's group (new-case + under-treatment), there was a significantly positive correlation between CXCL9 with NT-proBNP (p < 0.001, r = 0.703) and CXCL9 with HS-CRP (p = 0.015, r = 0.313). CONCLUSION: CXCL9 correlates significantly with well-established cardiovascular biomarkers, including HS-CRP and NT-ProBNP in RA patients. Key Points ⢠CXCL9 is an inflammatory marker in RA. ⢠CXCL9 has correlated with DAS-28. ⢠There is a strong correlation between CXCL9 with NT-proBNP and HS-CRP.
Assuntos
Artrite Reumatoide , Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/etiologia , Proteína C-Reativa/metabolismo , Peptídeo Natriurético Encefálico , Biomarcadores , Artrite Reumatoide/complicações , Fragmentos de Peptídeos , Mediadores da Inflamação , Quimiocina CXCL9RESUMO
Cardiovascular disease (CVD) is the most common cause of mortality in rheumatoid arthritis (RA), and Inflammation has a decisive role in its pathogenesis. CXCL9 contributes to multi aspects of inflammatory reactions associated with the pathogenesis of CVD. In the current study, we evaluated the association of plasma CXCL9 and CXCR3 gene expression with Cardiovascular risk factors in RA patients for the first time. Thirty newly diagnosed, 30 on-treatment RA patients, and 30 healthy subjects were recruited in this study. The plasma concentration of CXCL9 and CXCR3 gene expression were measured using ELISA and Real-Time PCR, respectively. The CVD risk was evaluated using Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE). The plasma levels of CXCL9 were significantly higher in the newly diagnosed and on-treatment RA patients compared to the control group (P < 0.0001 and P < 0.001, respectively). Also, The CXCR3 gene expression was strongly elevated in newly diagnosed and on-treatment patients (P < 0.001 and P < 0.01, respectively). The CXCL9 and CXCR3 were significantly associated with RA disease activity (P = 0.0005, r = 0.436; P = 0.0002, r = 0.463, respectively). The FRS was remarkably higher in newly diagnosed and on-treatment patients (P = 0.014 and P = 0.035, respectively). The CXCR3 gene expression significantly correlated with age, systolic blood pressure, FRS, and SCORE (P = 0.020, r = 0.298; P = 0.006, r = 0.346; P = 0.006, r = 0.349; P = 0.007, r = 0.341, respectively). The CXCL9 plasma concentration had a significant negative correlation with plasma HDL and LDL levels (P = 0.033, r = -0.275; P = 0.021, r = -0.296, respectively). CXCL9 and CXCR3 correlates with different variables of CVD in RA.
Assuntos
Artrite Reumatoide , Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Fatores de Risco , Artrite Reumatoide/metabolismo , Quimiocina CXCL9 , Inflamação , Fatores de Risco de Doenças Cardíacas , Receptores CXCR3/metabolismo , Quimiocina CXCL10RESUMO
Autoantibodies (AABs) play a critical role in the pathogenesis of autoimmune diseases (AIDs) and serve as a diagnostic and prognostic tool in assessing these complex disorders. Viral infections have long been recognized as a principal environmental factor affecting the production of AABs and the development of autoimmunity. COVID-19 has primarily been considered a hyperinflammatory syndrome triggered by a cytokine storm. In the following, the role of maladaptive B cell response and AABs became more apparent in COVID-19 pathogenesis. The current review will primarily focus on the role of extrafollicular B cell response, Toll-like receptor-7 (TLR-7) activation, and neutrophil extracellular traps (NETs) formation in the development of AABs following SARS-CoV-2 infection. In the following, this review will clarify how these AABs dysregulate immune response to SARS-CoV-2 by disrupting cytokine function and triggering neutrophil hyper-reactivity. Finally, the pathologic effects of these AABs will be further described in COVID-19 associate clinical manifestations, including venous and arterial thrombosis, a multisystem inflammatory syndrome in children (MIS-C), acute respiratory distress syndrome (ARDS), and recently described post-acute sequelae of COVID-19 (PASC) or long-COVID.