RESUMEN
Cystatin C (CysC) is a protein considered as an excellent marker of renal function, and it has been suggested as an independent predictor of cardiovascular (CV) risk. We evaluated the association of serum CysC with renal function, CV risk factors, inflammation, and subclinical atherosclerosis in Systemic Lupus Erythematosus (SLE) patients. Sixty-one SLE female patients were selected according to estimated glomerular filtration rate (GFR) > 60 ml/min/1.73m2. Renal function parameters, SLE specific factors, CV risk factors, and inflammatory markers were assessed. Subclinical atherosclerosis was assessed by measuring the carotid-femoral pulse wave velocity (PWV) by Doppler velocimetry. Serum CysC concentration was measured using a particle-enhanced immunonephelometric assay that established 0.59-1.01 mg/l as reference values. Patients with high CysC showed significantly altered creatinine, microalbuminuria, and GFR in addition to a significant higher presence of traditional CV risk factors such as arterial hypertension (p < 0.001), metabolic syndrome (p < 0.001), hypertrigliceridemia (p < 0.001), tobacco habit (p < 0.05), and a strong association with arterial stiffness (p = 0.017). Positive correlation between CysC, homocysteine (r = 0.511; p < 0.001) and fibrinogen levels (r = 0.304; p < 0.02) were also observed. A significantly higher SLICC/ACR score was related to high CysC level (p = 0.011), together with higher endothelin-1 and lower TNF serum concentration (p < 0.005). Considering only patients without any renal impairment (microalbumin/creatinine <30 mg/g), no association between CysC level and CV risk factors, arterial stiffness, or SLE-related factors was found. Serum CysC is a good marker of renal function in SLE patients, but it is not independently associated with cardiovascular risk factor or subclinical atherosclerosis.
Asunto(s)
Aterosclerosis/sangre , Enfermedades Cardiovasculares/sangre , Cistatina C/sangre , Tasa de Filtración Glomerular/fisiología , Riñón/fisiopatología , Lupus Eritematoso Sistémico/sangre , Adulto , Anciano , Anciano de 80 o más Años , Aterosclerosis/etiología , Aterosclerosis/fisiopatología , Biomarcadores/sangre , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/fisiopatología , Creatinina/sangre , Estudios Transversales , Citocinas/sangre , Femenino , Humanos , Pruebas de Función Renal , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/fisiopatología , Persona de Mediana Edad , Factores de Riesgo , Adulto JovenRESUMEN
Genetic variants of endosomal toll like receptors (TLR) have been associated with many infectious, autoimmune and inflammatory diseases, but few studies have been reported in the Spanish population. The aim of this study was to describe the allelic and genotypic distributions of some common nucleotide substitutions of endosomal TLRs in healthy Spanish women and to compare them with those already published in other population groups. Nine substitutions were analysed in 150 DNA samples from 150 Spanish, non-related healthy females: TLR3 rs3775291 and rs5743305; TLR7 rs179008 and rs5743781; TLR8 rs3764880 and TLR9 rs187084, rs5743836, rs352139 and rs352140. Genotyping was carried out by real time PCR and melting curve analysis in a LightCycler 480. A systematic review was performed in order to compare the genotypic distributions in our cohort with those previously published in other population groups. The comparative study was performed with the two tailed Fisher's test or the Yates continuity correction for the Chi-square test when appropriate. No homozygotes for rs5743781 in TLR7 were found, and rs352139 and rs352140 of TLR9 were in strong linkage disequilibrium. Genotype distributions in endosomal TLR are similar to other Spanish series previously reported. As expected, most differences were found when comparing our distributions with Asiatics, but differences were also found with other Caucasian populations. Since there are significant variations in genotypic distributions of TLRs in both interracial groups and within the same ethnic group, to carry out studies of disease susceptibility in more restricted groups is mandatory.
Asunto(s)
Sustitución de Aminoácidos , Pueblo Asiatico/genética , Receptores Toll-Like/genética , Población Blanca/genética , Adulto , Femenino , Voluntarios Sanos , Humanos , España , Receptor Toll-Like 3/genética , Receptor Toll-Like 7/genética , Receptor Toll-Like 8/genética , Receptor Toll-Like 9/genética , Adulto JovenRESUMEN
Cryofibrinogenemia is a rare clinical finding with a yet unknown physiopathogenic mechanism. We describe the case of a woman with cold-induced extensive necrotic lesions that responded poorly to initial corticosteroid and anticoagulant therapies. Serum cryoglobulin determinations were persistently negative. After several years of evolution, she developed severe cold-related skin lesions that required left-leg amputation. Further analysis disclosed the presence of cryofibrinogen and an apparently insignificant serum monoclonal immunoglobulin Gκ peak. We additionally demonstrate that the cold precipitation of fibrinogen was directly related to the monoclonal paraprotein presence. The lesions responded dramatically to a B cell-targeted therapy with intravenous cyclophosphamide and dexamethasone.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Crioglobulinemia/tratamiento farmacológico , Crioglobulinemia/inmunología , Ciclofosfamida/uso terapéutico , Dexametasona/uso terapéutico , Paraproteínas/inmunología , Anticuerpos Monoclonales/sangre , Crioglobulinas/inmunología , Quimioterapia Combinada , Femenino , Fibrinógenos Anormales/inmunología , Humanos , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVE: Endothelial progenitor cells (EPCs) play an important role in vascular damage repair and it has been suggested that a decreased number of these cells is associated with increased subclinical atherosclerosis. Our study aim was to evaluate whether the number of circulating EPCs in patients with SLE is associated with subclinical atherosclerosis, the presence of cardiovascular (CV) risk factors and SLE-specific factors. METHODS: Forty-six female SLE patients were included. At the time of each patient's appointment, CV risk factors, SLE-specific factors and EPCs were assessed in peripheral blood by flow cytometry. Simultaneously, atherosclerosis was assessed by measuring the carotid-femoral pulse wave velocity (PWV) by Doppler velocimetry, intima media thickness (IMT) and carotid plaque by B-mode US scanning. RESULTS: Patients were classificated according to PWV following the reference values adjusted by age and blood pressure published by the European Society of Cardiology. Patients with pathological values of PWV showed a significant decrease of circulating EPC percentage compared with normal PWV patients. Decreased EPC counts were also associated with certain risk factors, including hypertension, tobacco use, impaired glucose metabolism, and metabolic syndrome, and correlate with high levels of high-sensitivity CRP (hsCRP) or fibrinogen. The presence of carotid plaque and IMT measurement were unrelated with EPC quantification. CONCLUSION: Patients with a reduced percentage of EPCs showed pathological arterial stiffness and association with certain CV risk factors, suggesting that the measurement of circulating EPCs can be used as a biological marker to determine subclinical atherosclerosis in SLE.
Asunto(s)
Aterosclerosis/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Células Endoteliales/citología , Lupus Eritematoso Sistémico/fisiopatología , Células Madre/citología , Adulto , Enfermedades Asintomáticas , Aterosclerosis/sangre , Aterosclerosis/etiología , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/etiología , Grosor Intima-Media Carotídeo , Estudios Transversales , Femenino , Citometría de Flujo , Humanos , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/complicaciones , Persona de Mediana Edad , Análisis de la Onda del Pulso , Factores de Riesgo , Rigidez Vascular , Adulto JovenAsunto(s)
Antirreumáticos/uso terapéutico , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Síndrome de Schnitzler/tratamiento farmacológico , Anciano , Evaluación de Medicamentos , Femenino , Humanos , Inmunoglobulina M/sangre , Cadenas kappa de Inmunoglobulina/sangre , Inmunosupresores/uso terapéutico , Interleucina-1beta/antagonistas & inhibidores , Interleucina-1beta/fisiología , Paraproteínas/análisis , Inducción de Remisión , Síndrome de Schnitzler/sangre , Síndrome de Schnitzler/complicaciones , Síndrome de Schnitzler/fisiopatología , Tiroiditis Autoinmune/complicaciones , Resultado del TratamientoAsunto(s)
Enfermedades del Nervio Óptico/etiología , Sarcoidosis/complicaciones , Adulto , Femenino , HumanosRESUMEN
Cardiac myxoma cells have been demonstrated to produce interleukin (IL)-6, but its role in the systemic and immunologic manifestations of patients with this tumor is controversial. There is no evidence of any other source of such cytokine, but here we report a case of myxoma with systemic manifestations at diagnosis in which we evaluated the IL-6 production by peripheral blood cells before and after surgical tumor resection. Peripheral blood mononuclear cells were isolated by density gradient centrifugation, and the IL-6 expression in monocytes and lymphocytes was evaluated by flow cytometry. Before surgery, 74.4% of monocytes produced IL-6, but 1 month after surgery, a decrease in both the number of monocytes and the percentage of these cells expressing IL-6 was found along with an improvement of systemic and immunologic manifestations. Here, we demonstrated for the first time that monocytes contribute to the elevated production of IL-6 in patients with myxoma.
Asunto(s)
Neoplasias Cardíacas/metabolismo , Interleucina-6/biosíntesis , Monocitos/metabolismo , Mixoma/metabolismo , Anciano , Femenino , Neoplasias Cardíacas/patología , Humanos , Mixoma/patologíaRESUMEN
OBJECTIVE: To investigate the contribution of T lymphocytes and monocytes to cytokine production in systemic lupus erythematosus (SLE). METHODS: Forty-five SLE patients and 19 healthy volunteers were included. Serum levels of tumor necrosis factor alpha (TNFalpha), interferon gamma (IFN gamma), interleukin (IL)-6, and IL10 were quantified by ELISA. The cytokine production capacities of peripheral blood mononuclear cells were assessed by culturing in vitro with PMA+Ionomycin or LPS. The intracellular cytokine expression was measured by flow cytometry in T lymphocytes and monocytes, respectively. The influence of the disease activity (measured as the SLE-disease activity index; SLEDAI) and the treatment the patients were receiving was evaluated. RESULTS: Serum IL10, IL6, and TNFalpha levels were increased in patients (P Asunto(s)
Interleucina-10/metabolismo
, Interleucina-6/metabolismo
, Lupus Eritematoso Sistémico/inmunología
, Monocitos/patología
, Linfocitos T/patología
, Adolescente
, Adulto
, Estudios de Casos y Controles
, Células Cultivadas
, Femenino
, Humanos
, Interferón gamma/sangre
, Interferón gamma/metabolismo
, Interleucina-10/sangre
, Interleucina-6/sangre
, Lupus Eritematoso Sistémico/sangre
, Lupus Eritematoso Sistémico/metabolismo
, Lupus Eritematoso Sistémico/terapia
, Masculino
, Persona de Mediana Edad
, Monocitos/metabolismo
, Linfocitos T/metabolismo
, Factor de Necrosis Tumoral alfa/sangre
, Factor de Necrosis Tumoral alfa/metabolismo
, Adulto Joven
RESUMEN
OBJECTIVE: The development of common variable immunodeficiency (CVID) or hypogammaglobulinemia in systemic lupus erythematosus (SLE) is rare. The purpose of this article is to provide a detailed review of lupus-associated CVID and to identify clinical characteristics and laboratory features in patients with SLE-associated CVID. METHODS: We describe 2 patients with SLE and CVID and review the cases published in the English literature highlighting both the demographic and the clinical characteristics and the laboratory and therapeutic aspects of this disorder. RESULTS: Detailed descriptions of 18 patients were available; 89% were females with a mean age at the onset of SLE of 23.8 years. In 50% of patients CVID developed within the first 5 years after the diagnosis of SLE. All patients had been treated with corticosteroids and 72% had also received immunosuppressive therapy. Sinopulmonary infections were the most frequent symptom. SLE disease activity decreased after the development of CVID in 67% of patients. Most patients (89%) were treated with gammaglobulin therapy. The most notable immunological feature was a reduced number or percentage of B-cells in 60% of patients. CONCLUSIONS: CVID should be suspected in any SLE patient with recurrent sinopulmonary infections in the absence of SLE activity and/or immunosuppressive treatment.
Asunto(s)
Inmunodeficiencia Variable Común/complicaciones , Inmunoglobulinas Intravenosas/uso terapéutico , Lupus Eritematoso Sistémico/complicaciones , Subgrupos Linfocitarios/clasificación , Adolescente , Adulto , Inmunodeficiencia Variable Común/diagnóstico , Inmunodeficiencia Variable Común/tratamiento farmacológico , Femenino , Citometría de Flujo , Humanos , Lupus Eritematoso Sistémico/inmunologíaAsunto(s)
Bronquiectasia/etiología , Complejo Mycobacterium avium/aislamiento & purificación , Infección por Mycobacterium avium-intracellulare/complicaciones , Anciano de 80 o más Años , Antituberculosos/uso terapéutico , Bronquiectasia/tratamiento farmacológico , Tos/etiología , Quimioterapia Combinada , Femenino , Humanos , Infección por Mycobacterium avium-intracellulare/diagnóstico , SíndromeRESUMEN
BACKGROUND: Not all the patients with sarcoidosis need pharmacological therapy, and the decision to start therapy is based mainly on clinical conditions. The aim of this study was to evaluate the prognostic value of the leukocyte and lymphocyte subpopulations in the bronchoalveolar lavage fluid from these patients. METHODS: Thirty-three nonsmoking patients with sarcoidosis were included and classified based on the presence of Löfgren's syndrome (n = 11), the radiological stage (12 at Stage I, 17 at Stage II, and 4 at Stage III), and their follow-up. Differential leukocyte subsets and the lymphocyte subpopulations were determined by flow cytometry. RESULTS: The percentage of neutrophils was lower in patients with Löfgren's syndrome (P = 0.038) and in patients at Stage I (P = 0.002). Patients with a poor outcome had a higher percentage of neutrophils (P = 0.004) and NK cells (P = 0.023) than those with a stable disease. Finally, a higher percentage of NK cells was found in those patients who needed a steroid treatment (P = 0.012). CONCLUSIONS: Increased percentages of neutrophils and NK cells in the bronchoalveolar lavage fluid from patients with sarcoidosis are associated with a poor outcome and a higher probability to need steroids treatment. The percentage of neutrophils was also lower in patients with Löfgren's syndrome.