Endogenous stimulation is responsible for the high frequency of IL-17A-producing neutrophils in patients with rheumatoid arthritis.

BACKGROUND: Neutrophils play an important role in the pathogenesis of rheumatoid arthritis (RA). It has recently been reported that in addition to T helper (Th) 17 cells, other cells, including neutrophils, produce IL-17A, an important inflammatory cytokine involved in the pathogenesis of RA. The purpose of this study was to examine the presence of interleukin 17A-producing neutrophils in patients with RA. METHODS: We performed a cross-sectional study including 106 patients with RA and 56 healthy individuals. Whole peripheral blood cells were analyzed by flow cytometry to identify CD66b+ CD177+ IL-17A+ neutrophils and CD3+ CD4+ IL-17A+ T cells. Serum levels of IL-17A and IL-6 were measured by means of cytometry bead array (CBA). In purified neutrophils, mRNA levels of IL-17 and RORγ were measured by RT-PCR. In addition, purified neutrophils from patients and healthy controls were stimulated with the cytokines IL-6 and IL-23 to evaluate differences in their capacity to produce IL-17A. RESULTS: Neutrophils from RA patients expressed IL-17 and RORγ mRNA. Consequently, these cells also expressed IL-17A. Serum IL-17A levels but not Th17 cell numbers were increased in RA patients. Neutrophils positive for cytoplasmic IL-17A were more abundant in patients with RA (mean 1.2 ± 3.18%) than in healthy individuals (mean 0.07 ± 0.1%) (p < 0.0001). Although increased IL-17A+ neutrophil numbers were present in RA patients regardless of disease activity (mean 6.5 ± 5.14%), they were more frequent in patients with a more recent diagnosis (mean time after disease onset 3.5 ± 4.24 years). IL-6 and IL-23 induced the expression of RORγ but failed to induce IL-17A expression by neutrophils from RA patients and healthy individuals after a 3 h stimulation. CONCLUSION: IL-17A-producing neutrophils are increased in some RA patients, which are not related to disease activity but have an increased frequency in patients with recent-onset disease. This finding suggests that IL-17A-producing neutrophils play an early role in the development of RA.

Guía de práctica clínica para el manejo del lupus eritematoso sistémico propuesta por el Colegio Mexicano de Reumatología / Clinical practice guidelines for the treatment of systemic lupus erythematosus by the Mexican College of Rheumatology

Existen varias guías de práctica clínica tanto nacionales como internacionales para el tratamiento del lupus eritematoso sistémico. No obstante, la mayoría de las guías disponibles no están diseñadas para población mexicana o solamente son para el manejo de manifestaciones específicas como nefritis lúpica o para algún estado fisiológico como el embarazo. El Colegio Mexicano de Reumatología se propuso elaborar unas guías de práctica clínica que conjuntaran la mayor parte de las manifestaciones de la enfermedad y que incluyeran adicionalmente pautas en situaciones controversiales como lo son la vacunación y el periodo perioperatorio. En el presente documento se presenta la «Guía de práctica clínica para el manejo del lupus eritematoso sistémico» propuesta por el Colegio Mexicano de Reumatología, que puede ser de utilidad principalmente a médicos no reumatólogos que se ven en la necesidad de tratar a pacientes con lupus eritematoso sistémico sin tener la formación de especialistas en reumatología. En esta guía se presentan recomendaciones sobre el manejo de manifestaciones generales, articulares, renales, cardiovasculares, pulmonares, neurológicas, hematológicas, gastrointestinales, respecto a la vacunación y al manejo perioperatorio

There are national and international clinical practice guidelines for systemic lupus erythematosus treatment. Nonetheless, most of them are not designed for the Mexican population or are devoted only to the treatment of certain disease manifestations, like lupus nephritis, or are designed for some physiological state like pregnancy. The Mexican College of Rheumatology aimed to create clinical practice guidelines that included the majority of the manifestations of systemic lupus erythematosus, and also incorporated guidelines in controversial situations like vaccination and the perioperative period. The present document introduces the «Clinical Practice Guidelines for the Treatment of Systemic Lupus Erythematosus» proposed by the Mexican College of Rheumatology, which could be useful mostly for non-rheumatologist physicians who need to treat patients with systemic lupus erythematosus without having the appropriate training in the field of rheumatology. In these guidelines, the reader will find recommendations on the management of general, articular, kidney, cardiovascular, pulmonary, neurological, hematologic and gastrointestinal manifestations, and recommendations on vaccination and treatment management during the perioperative period

Clinical practice guidelines for the treatment of systemic lupus erythematosus by the Mexican College of Rheumatology. / Guía de práctica clínica para el manejo del lupus eritematoso sistémico propuesta por el Colegio Mexicano de Reumatología.

There are national and international clinical practice guidelines for systemic lupus erythematosus treatment. Nonetheless, most of them are not designed for the Mexican population or are devoted only to the treatment of certain disease manifestations, like lupus nephritis, or are designed for some physiological state like pregnancy. The Mexican College of Rheumatology aimed to create clinical practice guidelines that included the majority of the manifestations of systemic lupus erythematosus, and also incorporated guidelines in controversial situations like vaccination and the perioperative period. The present document introduces the «Clinical Practice Guidelines for the Treatment of Systemic Lupus Erythematosus¼ proposed by the Mexican College of Rheumatology, which could be useful mostly for non-rheumatologist physicians who need to treat patients with systemic lupus erythematosus without having the appropriate training in the field of rheumatology. In these guidelines, the reader will find recommendations on the management of general, articular, kidney, cardiovascular, pulmonary, neurological, hematologic and gastrointestinal manifestations, and recommendations on vaccination and treatment management during the perioperative period.

[Regulatory T cells in chronic obstructive pulmonary disease]. / Las células T reguladoras en la enfermedad pulmonar obstructiva crónica.

Exposition to tobacco smoke has been established as the main risk factor to develop chronic obstructive pulmonary disease (COPD), by inducing inflammation of the airways. Several cell populations participate in this inflammatory process. It has been accepted that a maladaptive modulation of inflammatory responses plays a critical role in the development of the disease. Regulatory T cells (Treg) are a subset of T CD4(+) lymphocytes that modulate the immune response through secretion of cytokines. The role of the Treg cells in chronic obstructive pulmonary disease is not clearly known, that is why it is important to focus in understanding their participation in the pathogenesis of the disease. To elaborate a systematic review of original articles in which we could describe Treg cells (their ontogeny, mechanisms of action) and their role in COPD, we made a systematic literature search in some data bases (MEDLINE, AMED, PubMed and Scielo) looking through the next keywords: "COPD and Regulatory T cells/EPOC y células T reguladoras", «Inflammation and COPD/Inflamación y EPOC¼, «Regulatory T cells/Células T reguladoras¼. We included basic science articles, controlled and non-controlled clinical trials, meta-analysis and guides. From this search we conclude that Treg cells are a subpopulation of T CD4(+) lymphocytes and their major functions are the suppression of immune responses and the maintenance of tolerance to self-antigens. A disruption in the regulatory mechanisms of the Treg cells leads to the development and perpetuation of inflammation in COPD.

Las células T reguladoras en la enfermedad pulmonar obstructiva crónica / Regulatory T cells in chronic obstructive pulmonary disease

La exposición al humo del tabaco induce inflamación de las vías aéreas y es el principal factor de riesgo para desarrollar la enfermedad pulmonar obstructiva crónica (EPOC). En este proceso inflamatorio participan varias poblaciones celulares. Algunas fallas en la modulación de la respuesta inflamatoria han sido aceptadas como un factor para el desarrollo de esta enfermedad. Las células T reguladoras (Treg) son un tipo de linfocitos T CD4+ que modulan la respuesta inmune mediante contacto directo con las células efectoras, así como por la secreción de citocinas inmunorreguladoras. El papel de las células Treg en la EPOC no se encuentra completamente comprendido, por lo cual es importante evaluar su participación en la inmunopatogénesis de la enfermedad. Con el objetivo de elaborar una revisión sistemática de artículos originales que nos permitiera describir las células Treg (su origen, características y mecanismos de acción) y su participación en la EPOC, realizamos una búsqueda intencionada en las siguientes bases electrónicas: MEDLINE, AMED, PubMed y Scielo; para ello usamos la combinación de las siguientes palabras clave: <

Exposition to tobacco smoke has been established as the main risk factor to develop chronic obstructive pulmonary disease (COPD), by inducing inflammation of the airways. Several cell populations participate in this inflammatory process. It has been accepted that a maladaptive modulation of inflammatory responses plays a critical role in the development of the disease. Regulatory T cells (Treg) are a subset of T CD4+ lymphocytes that modulate the immune response through secretion of cytokines. The role of the Treg cells in chronic obstructive pulmonary disease is not clearly known, that is why it is important to focus in understanding their participation in the pathogenesis of the disease. To elaborate a systematic review of original articles in which we could describe Treg cells (their ontogeny, mechanisms of action) and their role in COPD, we made a systematic literature search in some data bases (MEDLINE, AMED, PubMed and Scielo) looking through the next keywords: ''COPD and Regulatory T cells/EPOC y células T reguladoras'', <

In vivo peripheral blood proinflammatory T cells in patients with ankylosing spondylitis.

OBJECTIVE: Previous reports have shown an increase in peripheral blood mononuclear cells' (PBMC) Th17 cell subpopulation and tumor necrosis factor-α (TNF-α) secretion after in vitro stimulation with anti-CD3/CD28 or phorbol myristate acetate/ionomycin in ankylosing spondylitis (AS). The aim of our study was to determine whether there is a Th17 polarization not subjected to in vitro stimulation in patients with AS. METHODS: Nonstimulated PBMC were analyzed from 46 patients with AS, including 7 (15.2%) receiving tumor necrosis factor-α (TNF-α) inhibitors, 20 patients with rheumatoid arthritis, and 25 healthy controls. The surface phenotype of freshly isolated PBMC was determined by flow cytometry. Th1, Th2, Th17, and Treg subsets were defined as CD3+CD4+IFN-γ+, CD3+CD4+IL-4+, CD3+CD4+IL-17A+, and CD3+CD4+FoxP3+, respectively. Serum cytokines and interleukin 8 (IL-8) levels were quantified by Luminex technology. RESULTS: The percentages of Th17 and Th1 cells in AS were higher than in healthy controls (7.4% ± 1.8% vs 0.7% ± 0.2% and 4.0% ± 1.3% vs 1.1% ± 0.3%, respectively; p < 0.0001). Th17 and Th1 cell subsets in patients taking TNF-α inhibitors were lower than in those naive to such therapeutics and similar to healthy controls. Serum levels of IL-6, IL-17A, TNF-α, and IL-8 were significantly higher in patients with AS compared to controls. CONCLUSION: The percentages of Th17 and Th1 cells in PBMC without in vitro stimulation, as well as cytokine and IL-8 levels, were significantly increased in patients with AS compared with healthy controls. These T cell subsets and cytokine profiles of patients with AS taking TNF-α inhibitors were similar to those of healthy controls.

Increase of Th17 cells in peripheral blood of patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive disorder characterized by an inflammatory response to cigarette smoke. A disorder in immune regulation contributing to the pathogenesis of COPD has been suggested, however, little is known about the involvement of CD4 (+) T cells. To determine the distribution of different CD4(+) T cell subsets in patients with COPD, current smokers without COPD (CS) and healthy subjects (HS), and its correlation with pulmonary function. METHODS: Th1, Th2, Th17 and Treg, subsets, were quantified by flow cytometry in peripheral blood (PB) of 39 patients with COPD, 14 CS and 15 HS. Correlations were assessed with Spearman's rank test. The association between Th17 and lung function was evaluated with a multivariate logistic regression analysis. RESULTS: An increase of Th17 cells (median 9.7% range 0.8-22.5%) was observed in patients with COPD compared with CS (median 2.8% range 0.8-10.6) and HS (median 0.6% range 0.4-1%, p < 0.0001). Th1 and Tregs subsets were also increased in COPD and CS compared to HS. Inverse correlations were found between Th17 with FEV(1)%p r = -0.57 and with FEV(1)/FVC r = -0.60, (p < 0.0001 for both comparison). In addition, increase of Th17 predicted the presence [OR 1.76 (CI 95% 1.25-2.49, p = 0.001)] and severity of airflow limitation [OR 1.13 (CI95% 1.02-1.25, p = 0.02)]. CONCLUSIONS: The increase of Th17 response and the lost of balance between CD4(+) T cell subsets, suggest a lack of regulation of the systemic inflammatory response that may contribute to pathogenesis in COPD patients.

[Non-hypothermic J wave in subarachnoid hemorrhage]. / Onda J no hipotérmica en hemorragia subaracnoidea.

Incidence of electrocardiographic abnormalities in subarachnoid hemorrhage secondary to aneurysm rupture is 50-100%. The most frequent electrocardiographic abnormalities described include acuminated, inverted or flat T waves, inverted T waves associated with prolonged QT interval, positive or negative ST segment levels, prominent U waves, PR segment enlargement, acuminated P waves, and pathologic Q waves. J point is the isoelectric union of QRS complex with ST segment. It represents the end of depolarization and the beginning of repolarization. Prominent and positive J point level is named J wave, considered pathognomonic of severe hypothermia, although it has also been described in other clinical entities not associated with hypothermia, such as hypercalcemia, Brugada syndrome, acute brain injury, cardiac arrest, and dysfunction of cervical sympathetic system. Non-hypothermic J wave is an infrequent electrocardiographic manifestation of subarachnoid hemorrhage. We describe a clinical case of non-hypothermic J wave in a patient with subarachnoid hemorrhage.