CD4+CD25+CD127loFOXP3+ cell in food allergy: Does it predict anaphylaxis?

Background: Food allergy (FA), hence the incidence of food anaphylaxis, is a public health problem that has increased in recent years. There are still no biomarkers for patients with FA to predict severe allergic reactions such as anaphylaxis. Objective: There is limited information on whether regulatory T (Treg) cell levels are a biomarker that predicts clinical severity in cases presenting with FA, and which patients are at a greater risk for anaphylaxis. Methods: A total of 70 children were included in the study: 25 who had IgE-mediated cow’s milk protein allergy (CMPA) and presented with non-anaphylactic symptoms (FA/A−), 16 who had IgE-mediated CMPA and presented with anaphylaxis (FA/A+) (a total of 41 FA cases), and a control group consisting of 29 children without FA. The study was conducted by performing CD4+CD25+CD127loFOXP3+ cell flow cytometric analysis during resting at least 2 weeks after the elimination diet to FA subjects. Results: When the FA group was compared with healthy control subjects, CD4+CD25+CD127loFOXP3+ cell rates were found to be significantly lower in the FA group (p < 0.001). When the FA/A− and FA/A+ groups and the control group were compared in terms of CD4+CD25+CD127loFOXP3+ cell ratios, they were significantly lower in the FA/A− and FA/A+ groups compared to the control group (p < 0.001). Conclusions: Although there was no significant difference between the FA/A+ group and the FA/A− group in terms of CD4+CD25+CD127loFOXP3+ cells, our study is important, as it is the first pediatric study we know to investigate whether CD4+CD25+CD127loFOXP3+ cells in FA predict anaphylaxis (AU)

Association between environmental exposure and CD4+CD25+ regulatory T cells

Background: It is considered that farm areas protect young patients from allergy and asthma due to high exposure to endotoxins. Aim: To compare CD4+/CD25+ T-regulatory cells and forkhead transcription factor Foxp3 expression in asthmatic children allergic to house dust mites (HDM) living in rural and farm areas. Materials and Methods: This was a prospective analysis of 35 children living in farm areas (n = 19) and rural areas (n = 16), aged 8-16, with allergic rhinitis (allergic to dust mites) and newly diagnosed asthma. Surface molecule CD4+CD25+Foxp3+ expression on cultured PBMCs was estimated by flow cytometry using fluorophore-conjugated monoclonal antibodies in each patient. Results: Thirty-five children were included into the analysis: 19 children living in farm areas and 16 in rural areas. Within and between-groups (farm area vs. rural area) differences in CD4+/CD25+ and CD4+/CD25+Foxp3+ cell expression did not reach the level of significance. Conclusion: The current analysis showed that CD4+/CD25+ and CD4+/CD25+Foxp3+ cell expression was not associated with place of living in asthmatic children sensitive to HDM

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Taller de GECLID: Determinación de CD25 soluble en suero / No disponible

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Expansion of a CD26 low effector TH subset and reduction in circulating levels of sCD26 in stable allergic asthma in adults

Background: The pathogenesis of asthma is dependent on the balance between regulatory and effector T cells, which display differential expression of CD25 and CD26. Therefore, alteration of circulating levels of sCD25 and sCD26 during allergic asthma could be conditioned by changes in leukocyte phenotype. Objectives: To analyze expression of CD25 and CD26 on T lymphocytes and their soluble derivatives (sCD25, sCD26) during stable phases of moderate-severe allergic asthma. Methods: Cross-sectional study with 2 adult cohorts of allergic asthmatics. Clinical, anthropometric, pulmonary, hematological, and biochemical parameters were measured. Phenotyping was performed with flow cytometry in both circulating and cultured leukocytes. Dipeptidyl peptidase 4 (DPP4) activity was assayed in culture supernatants. Results: In vitro studies revealed upregulation of CD26 on human T lymphocytes upon activation, especially under TH17-favoring conditions, and a correlation with soluble DPP4 activity (rs=0.641; P<.001). CD26 expression on lymphocytes was higher in asthmatics, while serum sCD26 was lower in women and patients. The latter finding could be associated with an expanded CD25 low/CD26 low /CD127 low subset of effector CD4 + T cells in allergic asthma, with no changes in Treg percentages. However, women showed an increased Teff/Treg ratio, which could explain their greater susceptibility to asthma. Conclusions: Allergic asthma causes an increment in CD25 low CD26Low helper T cells detected in stable stages. These changes are mirrored in serum and should be considered in the light of the downmodulating role of CD26 in major chemokines related to the pathogenesis of asthma such as CCL11 (eotaxin), CCL5 (RANTES), and CXCL12a (SDF-1alfa) (AU)

Introducción: La patogénesis del asma depende del equilibrio entre células T reguladoras y T efectoras, las cuales presentan distintos niveles de CD25 y CD26. Por tanto, la alteración de la concentración de sCD25 y sCD26 durante el asma alérgica podría estar condicionada por cambios en el fenotipo de los leucocitos. Objetivos: Analizar la expresión de CD25 y CD26 en linfocitos T y sus derivados solubles (sCD25 y sCD26) durante asma alérgica moderada-severa y en fases estables. Métodos: Estudio transversal con dos cohortes de adultos con asma alérgica. Se han medido parámetros clínicos, antropométricos, de función pulmonar, hematológicos y bioquímicos. Se ha hecho el fenotipado de leucocitos circulantes y en cultivo mediante citometría de flujo. Se ha analizado la actividad Dipeptidil peptidasa 4 (DPP4) en sobrenadantes de cultivo. Resultados: Los estudios in vitro mostraron un aumento de expresión de CD26 en linfocitos T humanos tras activación, especialmente en condiciones favorables para TH 17, y una correlación con la actividad DPP4 soluble (rs=0,641; p < 0,001). La expresión de CD26 en linfocitos fue mayor en asmáticos, mientras que sCD26 estaba reducido en sueros de mujeres y pacientes. Este último hallazgo podría ser relacionado con la expansión de una subpoblación CD25 low/CD26 low/CD127 low de células T CD4 + efectoras en asma alérgica, sin cambios en los porcentajes de Treg. Sin embargo, las mujeres mostraron un incremento del cociente Tef/Treg, lo cual podría explicar su mayor susceptibilidad al asma. Conclusiones: El asma alérgica causa un incremento de células TH CD25 low CD26 low durante fases no activas. Estos cambios se reflejan en suero y deberían tenerse en cuenta a la luz de la función inhibidora de CD26 sobre quimioquinas importantes relacionadas con la patogénesis del asma, como CCL11 (eotaxina), CCL5 (RANTES) o CXCL12a (SDF-1alfa)

Regulatory T and B cells in asthmatic women: variations from pregnancy to postpartum

Background and Objectives: Allergic asthma and rhinitis are common in pregnancy. The immune mechanisms underlying the effects of asthma on pregnancy and vice versa are not completely understood. The aim of this study was to investigate changes in regulatory T and B cells in asthmatic women from late pregnancy to postpartum. Methods: Four groups of women were enrolled for this study: asthmatic (n=23) and healthy (n=43) third trimester-pregnant women and asthmatic (n=33) and healthy (n=35) nonpregnant women. Pregnant women were also evaluated postpartum (>6 weeks after delivery). Blood samples were taken from each woman and flow cytometry was used to characterize circulating regulatory T cells (Tregs) and regulatory B cells (Bregs). Foxp3 expression was assessed in CD4DimCD25Hi Tregs. Results: Tregs did not vary significantly from pregnancy to postpartum in asthmatic or healthy women, but CD24HiCD38Hi Bregs decreased in pregnancy and increased significantly postpartum. Foxp3 expression in Tregs was also impaired during pregnancy in both asthmatic and healthy women, but recovered postpartum. Asthmatic pregnant women had higher Foxp3 expression levels than healthy pregnant women (P=.007), probably due to the use of control medication. Conclusions: Women with controlled asthma showed variations in regulatory cell subsets during pregnancy and postpartum. A similar pattern was observed for Foxp3 expression and CD24HiCD38Hi Bregs during this period, corroborating the interaction between Tregs and Bregs in immune responses. Considering the immunomodulatory potential of these immune mediators, more studies are needed to evaluate their relationship with asthma and rhinitis complications in pregnancy (AU)

Introducción y Objetivos: El asma y la rinitis alérgica son enfermedades comunes durante el embarazo. A pesar de ello, no están completamente esclarecidos los mecanismos inmunológicos del embarazo implicados en el asma y viceversa. Este trabajo tuvo como objetivo el estudiar la evolución de los linfocitos T y B reguladores en mujeres asmáticas embarazadas, desde fases tardías del embarazo hasta después del parto. Métodos: Se incluyeron cuatro grupos de mujeres para este estudio: mujeres embarazadas en su tercer trimestre, asmáticas (n = 24) y sanas (n = 43), y mujeres no embarazadas, asmáticas (n = 33) y sanas (n = 35). Las mujeres embarazadas también fueron evaluadas después del parto (> 6 semanas después del parto). Se tomaron muestras de sangre de cada mujer y se realizó citometría de flujo para caracterizar los linfocitos T y B reguladores circulantes. La expresión de Foxp3 se evaluó en los linfocitos T reguladores CD4DimCD25Hi. Resultados: En las mujeres embarazadas, tanto sanas como asmáticas, los linfocitos T reguladores no oscilaron de manera significativa desde el embarazo hasta después del parto. Sin embargo, en los linfocitos B reguladores CD24HiCD38Hi, se observó una disminución durante el embarazo que aumentó significativamente después del parto. La expresión de Foxp3 en los linfocitos T reguladores también se vio alterada durante el embarazo tanto en las mujeres embarazadas asmáticas como en las sanas, normalizándose en el posparto. No obstante, las mujeres asmáticas embarazadas presentaron niveles de expresión de Foxp3 superiores a los de las mujeres embarazadas sanas (p = 0,007), probablemente debido a la utilización de medicación de control. Conclusiones: Las mujeres con asma controlada, durante el embarazo y después del parto, presentan variaciones en los diferentes subtipos linfocitos reguladores. El similar comportamiento que se observa para la expresión de Foxp3 y los linfocitos B reguladores CD24HiCD38Hi apoya la interacción que se establece en la respuesta inmunitaria, entre los linfocitos T y B reguladores, durante este período. Teniendo en cuenta el potencial inmunomodulador de estos mecanismos, se necesitan más estudios para evaluar su relación con las complicaciones del asma y la rinitis durante el embarazo (AU)

Autoimmune hepatitis: from mechanisms to therapy / La hepatitis autoinmune: de los mecanismos al tratamiento

Autoimmune hepatitis (AIH) is a progressive inflammatory hepatopathy and an important cause of end-stage liver disease. Its aetiology remains unknown, though both genetic and environmental factors are involved in its development. The major mechanism of autoimmune liver damage involves immune reactions against host liver antigens. Numerical and functional defects of regulatory T-cells play a permissive role enabling autoimmune liver injury to occur and persist. The most typical features of AIH are female preponderance, hypergammaglobulinaemia, seropositivity for circulating autoantibodies and a picture of interface hepatitis on histology. Two types of AIH are distinguished according to serological profile: AIH type 1 patients are positive for anti-nuclear and/or anti-smooth muscle antibodies, whereas AIH type 2 patients are defined by the positivity for anti-liver kidney microsomal type 1 antibody and/or for anti-liver cytosol type 1 antibody. Clinical manifestations are variable, and AIH onset is often ill-defined, frequently mimicking acute hepatitis; its course may be fluctuating. AIH responds to immunosuppressive treatment in the majority of cases. Steroids with or without azathioprine should be instituted promptly upon diagnosis. Remission is achieved in some 80% of patients. For the remaining 20% of patients, alternative immunosuppressive agents such as mycophenolate mofetil and calcineurin inhibitors are an option. Liver transplantation should be considered for those patients who progress to cirrhosis and develop complications of end-stage liver disease, as well as for those presenting with acute liver failure; outcomes are excellent, although the disease may recur in the allograft (AU)

La hepatitis autoinmune (HAI) es una hepatopatía inflamatoria progresiva y una causa importante de insuficiencia hepática terminal. Su origen continúa siendo una incógnita, si bien influyen en su evolución factores tanto genéticos como ambientales. El principal mecanismo de daño hepático autoinmune son las reacciones inmunitarias contra los antígenos hepáticos del receptor. Los defectos numéricos y funcionales de los linfocitos T reguladores desempeñan un permisivo papel a la hora de propiciar que la enfermedad hepática autoinmune se produzca y perdure. Las particularidades más típicas de la HAI son el predominio femenino, hipergammaglobulinemia, seropositividad para autoanticuerpos circulantes e imagen de hepatitis de interfase en la histología. Se distinguen 2 tipos de HAI conforme a su perfil serológico: los pacientes con HAI tipo 1 dan positivo para anticuerpos antinucleares y/o antimúsculo liso, mientras que los pacientes con HAI tipo 2 dan positivo para el anticuerpo antimicrosomal de hígado tipo 1 y/o para el anticuerpo contra el citosol hepático 1. Los signos clínicos varían, y el inicio de la HAI suele estar mal definido, imitando hepatitis aguda; su evolución puede fluctuar. La HAI remite con tratamiento inmunodepresor en la mayoría de los casos. Los corticosteroides con o sin azatioprina deberían iniciarse inmediatamente después del diagnóstico. La remisión se consigue en alrededor del 80% de los pacientes. Para el 20% restante, una opción son los fármacos inmunodepresores, como el micofenolato de mofetilo o inhibidores de calcineurina. El trasplante hepático debe ser tenido en cuenta para aquellos pacientes que cursen con cirrosis y padezcan complicaciones de insuficiencia hepática terminal, así como para los que experimenten insuficiencia hepática aguda; los resultados son excelentes, si bien la enfermedad podría recidivar en el alotransplante (AU)

Mastocitosis sistémica: comunicación de 2 casos con presentación clínica semejante a linfoma / Two cases of systemic mastocytosis with a lymphoma-like presentation

Las mastocitosis son un grupo de trastornos neoplásicos clonales caracterizados por proliferación tisular de mastocitos morfológica y/o molecularmente anormales; son sistémicas cuando tienen localización extracutánea. El cuadro clínico es variable e inespecífico. Se han descrito casos asociados a otras neoplasias hematológicas, especialmente las de tipo mieloide y, en menor medida, linfoide. En la presente revisión informamos los casos de 2 mujeres en la sexta y séptima décadas de la vida con mastocitosis sistémica que involucraba la médula ósea, el ganglio linfático y la piel, con diagnóstico clínico inicial de linfoma en el que tras la reevaluación histológica con la coloración de Giemsa se identificaron mastocitos, agregados en acúmulos, morfológicamente anormales que fueron confirmados mediante la positividad para CD117, CD25 y CD45. Uno de los casos presentó una evolución clínica rápidamente desfavorable(AU)

Mastocytosis is a group of clonal neoplastic disorders characterized by tissue proliferation of mastocytes morphologically and/or molecularly abnormal, being systemic when it has extracutaneous location. The clinical picture is variable and nonspecific. Cases have been described associated to other hematological neoplasms, especially those of myeloid and, to a lesser extent, lymphoid type. We present two cases of systemic mastocytosis involving bone marrow, lymph nodes and skin in elderly female patients which were initially diagnosed clinically as lymphoma. However, an abnormal proliferation in cumulus of mastocytes was identificated histologically using Giemsa and confirmed by CD117, CD25 and CD45. One of the patients had a rapid, unfavorable clinical evolution(AU)

A study of circulating anti-CD25 antibodies in non-small cell lung cancer

PURPOSE: Tumors can trigger specific immune response to tumor-associated antigens but the precise mechanism remains unclear. Since regulatory T-lymphocytes (Treg) play a crucial role in controlling autoimmune responses, the present work was undertaken to test whether dysfunction of Treg cells could be involved in developing autoimmunity in patients with lung cancer. METHODS: In this study, we developed an in-house enzyme-linked immunosorbent assay to test circulating anti-CD25 autoantibodies among 272 patients with non-small cell lung cancer (NSCLC) and 226 control subjects matched in age, gender and smoking history. RESULTS: Mann-Whitney U test showed that the anti-CD25 IgG level was significantly higher in patients with NSCLC than control subjects (Z = -7.48, P < 0.001) while the anti-CD25 IgA level was not significantly changed in the patient group as compared with the control group (Z = -1.34, P = 0.181). Spearman correlation analysis failed to reveal a significant correlation between the levels of anti-CD25 IgG and IgA either in patients with NSCLC (r = -0.034, P = 0.578) or in control subjects (r = 0.055, P = 0.429). ROC analysis showed an AUC of 0.70 for anti-CD25 IgG, in which NSCLC at stage III had the highest AUC (0.75). The sensitivity against a specificity of >90 % was 35.0 % for anti-CD25 IgG assay with an inter-assay deviation of 9.4 %, and 4.0 % for anti-CD25 IgA assay with an inter-assay deviation of 13.0 %. CONCLUSIONS: Circulating anti-CD25 IgG antibody may be a useful biomarker for prognosis of lung cancer (AU)

FOXP3: Controlador maestro de la generación y función de las células reguladoras naturales / FOXP3: Master gene controlling the development and function of regulatory cells

El reconocimiento de subpoblaciones celulares reguladoras ha marcado una nueva etapa de desarrollo investigativo sobre la generación y control de la respuesta inmune. La subpoblación mejor caracterizada son loslinfocitos T CD4+CD25+FOXP3+.Uno de los grandes aportes a la comprensión de la regulación inmunees la identificación de FOXP3, un factor regulador de la transcripción, queparticipa directamente en la función de las células reguladoras T CD4+humanas y murinas. FOXP3 ha sido definido por diversos autores como elgen maestro controlador del desarrollo y función de las células reguladoras y es considerado el principal marcador molecular, a la fecha, de estasubpoblación reguladora.FOXP3 fue descrito inicialmente en ratones “escurfi”, los cuales presentan mutaciones espontáneas en el marco de lectura del gen denominado Foxp3. Este gen codifica para la proteína escurfina, cuya deficiencia estáasociada a trastornos autoinmunes y linfoproliferativos severos. En los (..) (AU)

The recognition of regulatory cell subpopulations has marked a newstage of development on the research of the generation and control of theimmune response. The best characterized subpopulation of T lymphocytes are the CD4+CD25+cells; in this population, FOXP3+has been identified as an associated phenotype, as this marker is not exclusive for thissubpopulation.One of the great contributions to the understanding of immune regulation is the identification of FOXP3, a regulatory transcription factordirectly involved in the function of human and mouse CD4+T regulatorycells. FOXP3 has been defined by various authors as the master gene controlling the development and function of regulatory cells and is considered the main marker for this regulatory subpopulation.FOXP3 was initially described in “scurfy” mice, which have spontaneous mutations in the reading frame of Foxp3. This gene encodes the (..) (AU)

T cells in sputum of asthmatic patients are activated independently of disease severity or control

Background: T cells play an important role in bronchial asthma. Although airway CD4+ T cells have been extensively studied previously, there are hardly any studies relating CD8+ T cell activation and disease symptoms. Objectives: The aim of this study was to analyse the association between T cell activation in induced sputum T cells and asthma severity and control; and to evaluate T cell subpopulations in the same subgroups. Methods: Fifty allergic asthmatic patients were recruited and lung function testing was performed. Airway cells were obtained by sputum induction via inhalation of hypertonic saline solution. CD3, CD4, CD8, CD28, CD25 and CD69 were studied by flow cytometry in whole induced sputum and peripheral blood cells. Results: Total induced sputum T cells and CD8+ T cells had a higher relative percentage of the activation markers CD25 and CD69 in comparison with peripheral blood. In sputum, the relative percentage of CD25 was higher in CD4+ T cells when compared to CD8+ T cells and the reverse was true regarding CD69. However, neither disease severity nor control were associated with the relative percentage of CD25 or CD69 expression on T cells in sputum. Conclusions: Both CD4+ and CD8+ T cells are activated in the lungs and peripheral blood of asthmatic patients. However, with the possible exception of CD69+ CD8+ T lymphocytes in the sputum, there is no association between T cell activation phenotype in the target organ and disease severity or control (AU)

Mecanismos inmunológicos de inducción de tolerancia a aloinjertos / No disponible

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