RESUMO
Around a 20-30% of inflammatory bowel disease (IBD) patients are diagnosed before they are 18 years old. Anti-TNF drugs can induce and maintain remission in IBD, however, up to 30% of patients do not respond. The aim of the work was to identify markers that would predict an early response to anti-TNF drugs in pediatric patients with IBD. The study population included 43 patients aged <18 years with IBD who started treatment with infliximab or adalimumab. Patients were classified into primary responders (n = 27) and non-responders to anti-TNF therapy (n = 6). Response to treatment could not be analyzed in 10 patients. Response was defined as a decrease in over 15 points in the disease activity indexes from week 0 to week 10 of infliximab treatment or from week 0 to week 26 of adalimumab treatment. The expression profiles of nine genes in total RNA isolated from the whole-blood of pediatric IBD patients taken before biologic administration and after 2 weeks were analyzed using qPCR and the 2-∆∆Ct method. Before initiation and after 2 weeks of treatment the expression of SMAD7 was decreased in patients who were considered as non-responders (p value < 0.05). Changes in expression were also observed for TLR2 at T0 and T2, although that did not reach the level of statistical significance. In addition, the expression of DEFA5 decreased 1.75-fold during the first 2 weeks of anti-TNF treatment in responders, whereas no changes were observed in non-responders. Expression of the SMAD7 gene is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD. TLR2 and DEFA5 need to be validated in larger studies.
Assuntos
Adalimumab/farmacologia , Anti-Inflamatórios/farmacologia , Antirreumáticos/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/farmacologia , Transcriptoma/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/uso terapêutico , Adolescente , Anti-Inflamatórios/uso terapêutico , Antirreumáticos/uso terapêutico , Criança , Pré-Escolar , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Lactente , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/genética , Infliximab/uso terapêutico , Masculino , RNA Mensageiro/biossíntese , RNA Mensageiro/sangue , RNA Mensageiro/genética , Receptores Tipo II do Fator de Necrose Tumoral/biossíntese , Receptores Tipo II do Fator de Necrose Tumoral/genética , Proteína Smad7/biossíntese , Proteína Smad7/genética , Receptor 2 Toll-Like/biossíntese , Receptor 2 Toll-Like/genética , Resultado do Tratamento , Receptor Gatilho 1 Expresso em Células Mieloides/biossíntese , Receptor Gatilho 1 Expresso em Células Mieloides/genética , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genética , alfa-Defensinas/biossíntese , alfa-Defensinas/genéticaRESUMO
Atherosclerosis is a chronic inflammatory disease of the arteries that can lead to thrombosis, infarction and stroke, underlying the first cause of mortality worldwide. Adaptive immunity plays critical roles in atherosclerosis, and numerous studies have ascribed both atheroprotective and atherogenic functions to specific subsets of T and B cells. However, less is known on how antigen specificity determines the protective or adverse outcome of such adaptive responses. Understanding antigen triggers in atherosclerosis is crucial to delve deeper into mechanisms of disease initiation and progression and to implement specific immunotherapeutic approaches, including vaccination strategies. Here we review the role of adaptive immunity in atherosclerosis and the insights that single-cell technology has provided into the function of distinct immune cell subsets. We outline the most relevant atherosclerosis antigens and antibodies reported to date and examine their immunotherapeutic potential. Finally, we review the most promising vaccination-based clinical trials targeting the adaptive immune system.