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Dig Dis Sci ; 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31858325


BACKGROUND: Increasing the interval of administration of anti-TNF agents over the duration specified in the data sheet is not common in inflammatory bowel disease (IBD). AIM: To evaluate the outcomes of IBD patients treated with this strategy. METHODS: Patients with IBD who were treated with infliximab or adalimumab at intervals > 8 weeks or > 2 weeks, respectively, because of persistent clinical remission, were identified at local databases of the ENEIDA registry (a nationwide registry promoted by the Spanish Working Group in Crohn's disease and Ulcerative Colitis-GETECCU) of two referral centers. Treatment success was considered if patients remained in clinical remission with the same schedule or without biological therapy at the end of follow-up, and if no return to the conventional schedule, dose-escalation, change in biological agent, or a course of systemic corticosteroids or surgery were required. RESULTS: Eighty-five patients were included, 60 treated with infliximab and 25 with adalimumab. The spaced schedule was initiated after a median of 25 months on anti-TNF treatment (IQR 14-49). Throughout a median follow-up of 34 months (IQR 21-47), fifty patients (59%) fulfilled the success criteria of the spaced strategy. No differences were found regarding type of IBD or anti-TNF agent. Baseline C-reactive protein levels and disease duration at the time of starting anti-TNF treatment were the only factors associated with treatment success. CONCLUSIONS: Anti-TNF administration at longer intervals than those provided in the data sheet may be an efficacious, convenient, and cheaper treatment option, particularly in patients in whom anti-TNF treatment was initiated early.

Drug Alcohol Depend ; 180: 7-13, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28850904


INTRODUCTION: Harmful alcohol consumption may have an impact on the adaptive immune system through an imbalance in T cell subpopulations and changes in cell activation. We aimed to analyze profiles of CD4 and CD8T cell activation in patients with alcohol use disorder (AUD). METHODS: We used a cross-sectional study with patients seeking treatment of the disorder. Blood samples for immunophenotyping were obtained at admission. Profiles of T cell activation were defined: (I) CD38+/HLA-DR+, (II) CD38+/HLA-DR-, (III) CD38-/HLA-DR+, (IV) CD38-/HLA-DR- and compared with healthy controls. We calculated a CD8+ T cell activation indicator (AI) that was defined as the quotient of non-activated cells (CD38-/HLA-DR-) and activated cells (CD38+/HLA-DR+). RESULTS: 60 patients were eligible (83%M); median age was 49 years [IQR: 44-54] and alcohol consumption was 145g/day [IQR: 90-205]. Mean±SD of CD38+/HLA-DR- was 50.3±50.6 cells/µL in patients and 33.5±24.5 cells/µL in controls (p=0.03), for the CD38-/HLA-DR+ it was 61±62.2 cells/µL in patients and 21.2±17.3 cells/µL in controls (p<0.001) and for the CD38+/HLA-DR+ it was 20.2±15.6 cells/µL in patients and 10.8±10.3 cells/µL in controls (p<0.001). In patients, an inverse correlation was observed between absolute number and percentage of CD4+ T cells, and the percentage of CD38+/HLA-DR+CD8+ T cells (r=0.37, p=0.003; r=0.2, p=0.086, respectively). CONCLUSIONS: Patients with AUD have an increased expression of immune activation with respect to healthy individuals. This excess of activated CD8+ T cells correlates with the absolute CD4+ T cells.

Transtornos Relacionados ao Uso de Álcool , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/química , Antígenos HLA-DR/imunologia , Ativação Linfocitária/imunologia , Estudos Transversais , Humanos , Imunofenotipagem
Drug Alcohol Depend ; 162: 124-9, 2016 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-27038675


BACKGROUND: Alcohol abuse impacts innate and adaptive immunity and predisposes to infections. However, prevalence and correlations of cellular immune alterations in large case series is underreported. We aimed to analyze quantitative alterations of T-lymphocyte subpopulations in patients with alcohol use disorder (AUD). METHODS: cross-sectional study in patients admitted for detoxification between January 1, 2002 and December 31, 2012. Socio-demographic and alcohol use characteristics and blood samples for biochemistry, hematology and immune phenotype was obtained at admission. RESULTS: 238 patients (79.8%M) were eligible; age at admission was 43 years (interquartile range [IQR]: 38-51 years), the amount of alcohol consumption was 180 g/day (IQR: 120-200 g/day) and median duration of AUD was 18 years (IQR: 9-25 years). Compared to healthy individuals, 50% of patients had significantly fewer double-negative (DN) T-lymphocytes (<34 × 10(9)/L) and 23% had more double-positive (DP) T-cells (>52 × 10(9)/L). In addition, 24% of patients had high number of CD8(+) cells (>735 × 10(9)/L) and 13% had low CD4(+) cell counts (<600 × 10(9)/L). In multivariable analysis, age, sex, serum albumin, and current cocaine use were predictors of T-cell subpopulation alterations. Women were three-times (OR=3.5, 95%CI:1.3-9.5) more likely to present with higher DP T-lymphocytes than men. CONCLUSIONS: Quantitative alterations of T-cell subpopulations are frequent in patients seeking treatment of AUD. Assessment of cellular immunity in this population may help to identify those at increased risk of immune alterations.

Transtornos Relacionados ao Uso de Álcool/imunologia , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos/efeitos dos fármacos , Subpopulações de Linfócitos T/efeitos dos fármacos , Adulto , Consumo de Bebidas Alcoólicas/imunologia , Consumo de Bebidas Alcoólicas/patologia , Transtornos Relacionados ao Uso de Álcool/patologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais
PLoS One ; 10(11): e0142186, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26555789


CD26 is a T cell activation marker consisting in a type II transmembrane glycoprotein with dipeptidyl peptidase IV (DPPIV) activity in its extracellular domain. It has been described that DPPIV inhibition delays the onset of type 1 diabetes and reverses the disease in non-obese diabetic (NOD) mice. The aim of the present study was to assess the effect of MK626, a DPPIV inhibitor, in type 1 diabetes incidence and in T lymphocyte subsets at central and peripheral compartments. Pre-diabetic NOD mice were treated with MK626. Diabetes incidence, insulitis score, and phenotyping of T lymphocytes in the thymus, spleen and pancreatic lymph nodes were determined after 4 and 6 weeks of treatment, as well as alterations in the expression of genes encoding ß-cell autoantigens in the islets. The effect of MK626 was also assessed in two in vitro assays to determine proliferative and immunosuppressive effects. Results show that MK626 treatment reduces type 1 diabetes incidence and after 6 weeks of treatment reduces insulitis. No differences were observed in the percentage of T lymphocyte subsets from central and peripheral compartments between treated and control mice. MK626 increased the expression of CD26 in CD8+ T effector memory (TEM) from spleen and pancreatic lymph nodes and in CD8+ T cells from islet infiltration. CD8+TEM cells showed an increased proliferation rate and cytokine secretion in the presence of MK626. Moreover, the combination of CD8+ TEM cells and MK626 induces an immunosuppressive response. In conclusion, treatment with the DPPIV inhibitor MK626 prevents experimental type 1 diabetes in association to increase expression of CD26 in the CD8+ TEM lymphocyte subset. In vitro assays suggest an immunoregulatory role of CD8+ TEM cells that may be involved in the protection against autoimmunity to ß pancreatic islets associated to DPPIV inhibitor treatment.

Linfócitos T CD8-Positivos/efeitos dos fármacos , Diabetes Mellitus Tipo 1/prevenção & controle , Dipeptidil Peptidase 4/efeitos dos fármacos , Inibidores da Dipeptidil Peptidase IV/farmacologia , Fosfato de Sitagliptina/análogos & derivados , Animais , Autoantígenos/genética , Linfócitos T CD8-Positivos/imunologia , Diabetes Mellitus Tipo 1/imunologia , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos NOD , Fosfato de Sitagliptina/farmacologia , Fator de Crescimento Transformador beta/sangue