Araceli Chico Capote

Proinflammatory Soluble Interleukin-15 Receptor Alpha Is Increased in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease in which many cytokines have been implicated. In particular, IL-15 is a cytokine involved in the inflammatory processes and bone loss. The aim of this study was to investigate the existence in synovial fluid of soluble IL-15Rα, a private receptor subunit for IL-15 which may act as an enhancer of IL-15-induced proinflammatory cytokines. Soluble IL-15Rα was quantified by a newly developed enzyme-linked immunosorbent assay (ELISA) in samples of synovial fluid from patients with RA and osteoarthritis (OA). The levels of IL-15Rα were significantly increased in RA patients compared to OA patients. Also, we studied the presence of membrane-bound IL-15 in cells from synovial fluids, another element necessary to induce pro-inflammatory cytokines through reverse signaling. Interestingly, we found high levels of IL-6 related to high levels of IL-15Rα in RA but not in OA. Thus, our results evidenced presence of IL-15Rα in synovial fluids and suggested that its pro-inflammatory effect could be related to induction of IL-6.Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease in which many cytokines have been implicated. In particular, IL-15 is a cytokine involved in the inflammatory processes and bone loss. The aim of this study was to investigate the existence in synovial fluid of soluble IL-15Rα, a private receptor subunit for IL-15 which may act as an enhancer of IL-15-induced proinflammatory cytokines. Soluble IL-15Rα was quantified by a newly developed enzyme-linked immunosorbent assay (ELISA) in samples of synovial fluid from patients with RA and osteoarthritis (OA). The levels of IL-15Rα were significantly increased in RA patients compared to OA patients. Also, we studied the presence of membrane-bound IL-15 in cells from synovial fluids, another element necessary to induce pro-inflammatory cytokines through reverse signaling. Interestingly, we found high levels of IL-6 related to high levels of IL-15Rα in RA but not in OA. Thus, our results evidenced presence of IL-15Rα in synovial fluids and suggested that its pro-inflammatory effect could be related to induction of IL-6.

Differential expression of pro-inflammatory cytokines IL-15Ralpha, IL-15, IL-6 and TNFalpha in synovial fluid from Rheumatoid arthritis patients

BackgroundPro-inflammatory cytokines are directly implicated in the pathogenesis of Rheumatoid arthritis (RA). Variable clinical response to cytokine targeted therapies as TNFalpha and IL-6, strongly highlights the heterogeneity of inflammatory process in RA. Another cytokine, IL-15 has also been related to the inflammatory process in RA. Recently we described for the first time, the presence of its specific receptor, IL-15Ralpha, in synovial fluid (SF). The aim of this work was to compare the expression profile of IL-15Ralpha, its ligand IL-15, TNFalpha and IL-6 and how these cytokines are correlated in SF from RA patients taking as a reference Osteoarthritis (OA), an articular but not autoinmmune disease.MethodsSynovial fluids were obtained from the knee joints of 60 patients, 30 with confirmed diagnosis of RA and 30 with OA diagnosis. The levels of TNFalpha, IL-6, IL-15 and IL-15Ralpha were measured by ELISA. A statistical analysis was performed with GraphPad Prism v5.0 using the Mann–Whitney U test and Spearman’s rank correlation. A cluster analysis was run in MeV software v4.9.0 and differences across clusters were evaluated by an ANOVA including post-test analysis.ResultsWe found higher and significant levels of TNFalpha, IL-6 and IL-15Ralpha but not of IL-15 in RA compared with the OA group. Additionally, a high inter-individual variability in the levels of these 4 cytokines was observed in RA, although we identified 4 patients’ subgroups by cluster analysis of cytokines concentration in SF. We also found a positive correlation between IL-15Ralpha-IL-6 and IL-15Ralpha-IL-15, but not for other pairs of cytokines in RA. In addition we found correlation between the value of IL-15Ralpha in SF and disease activity score, DAS28.ConclusionsIn our current work we found a high inter-individual variability in the levels of TNFalpha, IL-6, IL-15 and IL-15Ralpha in SF of RA patients and were identified four principal clusters of cytokines concentration in SF, suggesting the importance of identifying disease subset of patients for personalized treatment. Finally, we found a correlation between IL-15Ralpha-IL-6, IL-15Ralpha-IL-15, but we did not find any correlation between other pairs of studied cytokines in SF.

Prevalencia de enfermedad vascular aterosclerótica en pacientes cubanos con lupus eritematoso sistémico

La morbimortalidad asociada a enfermedad vascular aterosclerotica ha aumentado en los enfermos con lupus eritematoso sistemico (LES). Objetivos: Determinar la frecuencia con que se encuentra la enfermedad vascular aterosclerotica en nuestros pacientes, e identificar la asociacion de algunos factores de riesgo con su presencia. Metodo: El estudio incluyo a 51 pacientes y 51 controles identificados por edad, sexo y color de piel, a quienes se realizo ultrasonido de carotida para medir el grosor del complejo intima-media y determinar la presencia de placa. Se identificaron, en pacientes y controles, los factores de riesgos clasicos, como edad, habito tabaquico, hipertension arterial, diabetes mellitus e hiperlipemia. En los pacientes con LES se analizaron ademas las caracteristicas clinicas de la enfermedad y los tratamientos recibidos. Finalmente, se estudio la influencia de todas estas variables en la enfermedad vascular aterosclerotica de los pacientes con LES. Resultados: Los factores de riesgo fueron similares entre pacientes y controles con la excepcion de la hipertrigliceridemia mas frecuente en los pacientes. La presencia de placa fue mas prevalente en los pacientes que en los controles (el 56,9% frente al 23,5%, p = 0,001). En el analisis multivariable, la edad (odds ratio [OR] = 1,31; intervalo de confianza [IC] del 95%, 1,038-1,253; p = 0,005), el diagnostico de LES (OR = 3,872; IC del 95%, 1,4-10,2; p = 0,005) y el dano sistemico valorado por el indice de SLICC/ACR (OR = 3,884; IC del 95%, 1,1-12,9; p = 0,006) fueron las variables que de forma independiente se asociaron a la presencia de aterosclerosis en los pacientes con LES. Conclusiones: La frecuencia de aterosclerosis se encuentra aumentada en los pacientes con LES, y parece que podria estar asociada a otros factores de riesgo independientes a los clasicamente implicados en la aterosclerosis.UNLABELLED Atherosclerotic vascular disease-associated mortality and morbidity has increased in sick patients with with systemic erythematosus lupus (SLE). OBJECTIVES To determine frequency of atherosclerotic vascular disease (AVD) in our patients, and to identify associations of some risk factors associated to its presence. METHOD Study included 51 patients and 51 controls paired by age, sex, and skin colour, who underwent carotid ultrasound (US) to measure thickness of intimamedial complex, and to determine presence of plaques. In patients and controls we analyzed the presence of classic risk factors, eg age, smoking, high blood pressure, diabetes mellitus, and hyperlipidemia. In addition in SLE we also analyzed the influencie on AVD of the clinical features of disease, as well as treatments applied. RESULTS Risk factors were similar between patients and controls, except for hypertriglyeridemia, which was more frequent in patients. Presence of plaque was more prevalent in patients than in controls (59.9 vs 23.5%, P=.001). In multivariate analysis age (OR, 1.31; 95% CI, 1.038-1.253; P=.005), diagnosis of SLE (OR, = 3.872; CI 95%, 1.4-10.2; p = 0.005), and presence of damage by SLICC/ACR (OR, 34.884; 95% CI, 1.1-12.9; P=.006) were the only variables independently associated to the presence of atherosclerosis in our patients. CONCLUSIONS Frequency of atherosclerosis is increased in patients presenting with SLE, risk factors independent of those classics, seem to be associated with this presence.UNLABELLED Atherosclerotic vascular disease-associated mortality and morbidity has increased in sick patients with with systemic erythematosus lupus (SLE). OBJECTIVES To determine frequency of atherosclerotic vascular disease (AVD) in our patients, and to identify associations of some risk factors associated to its presence. METHOD Study included 51 patients and 51 controls paired by age, sex, and skin colour, who underwent carotid ultrasound (US) to measure thickness of intimamedial complex, and to determine presence of plaques. In patients and controls we analyzed the presence of classic risk factors, eg age, smoking, high blood pressure, diabetes mellitus, and hyperlipidemia. In addition in SLE we also analyzed the influencie on AVD of the clinical features of disease, as well as treatments applied. RESULTS Risk factors were similar between patients and controls, except for hypertriglyeridemia, which was more frequent in patients. Presence of plaque was more prevalent in patients than in controls (59.9 vs 23.5%, P=.001). In multivariate analysis age (OR, 1.31; 95% CI, 1.038-1.253; P=.005), diagnosis of SLE (OR, = 3.872; CI 95%, 1.4-10.2; p = 0.005), and presence of damage by SLICC/ACR (OR, 34.884; 95% CI, 1.1-12.9; P=.006) were the only variables independently associated to the presence of atherosclerosis in our patients. CONCLUSIONS Frequency of atherosclerosis is increased in patients presenting with SLE, risk factors independent of those classics, seem to be associated with this presence.

Prevalence of Atherosclerotic Vascular Disease in Cuban Patients With Systemic Lupus Erythematosus

Atherosclerotic vascular disease-associated mortality and morbidity has increased in sick patients with systemic lupus erythematosus (SLE). Objectives To determine frequency of atherosclerotic vascular disease (AVD) in our patients, and to identify associations of some risk factors associated to its presence. Method Study included 51 patients and 51 controls paired by age, sex, and skin colour, who underwent carotid ultrasound (US) to measure thickness of the intima-medial complex, and to determine presence of plaques. In patients and controls we analyzed the presence of classic risk factors, eg, age, smoking, high blood pressure, diabetes mellitus, and hyperlipidemia. In addition in SLE we also analyzed the influencie on AVD of the clinical features of disease, as well as treatments applied. Results Risk factors were similar between patients and controls, except for hypertriglyceridemia, which was more frequent in patients. Presence of plaque was more prevalent in patients than in controls (59.9% vs 23.5%, P =.001). In multivariate analysis, age (OR, 1.31; 95% CI, 1.038–1.253; P =.005), diagnosis of SLE (OR, 3.872; 95% CI, 1.4–10.2; P =.005), and the presence of damage measured by SLICC/ACR (OR, 34.884; 95% CI, 1.1–12.9; P =.006) were the only variables independently associated to the presence of atherosclerosis in our patients. Conclusions Frequency of atherosclerosis is increased in patients presenting with SLE, risk factors independent of those classics, seem to be associated with this presence.