Assessment of activated gut-homing CD8+ T cells in blood by flow cytometry during a 3-day gluten challenge.

Accurate celiac disease (CD) diagnosis must be performed in individuals following a gluten containing diet. Diagnostic procedures for individuals already on a gluten-free diet (GFD) avoiding long gluten reintroductions are still challenging. To deal with this issue, we developed an accurate but simple method that requires only a 3-day gluten challenge and circumvents the main limitations of previously suggested proposals such as requirement of specific peptides and unusual specialized lab facilities or high cost. In an attempt to standardize this methodology to be used in daily clinical practice, we describe here an optimized protocol for assessing activated gut-homing CD8+ T cells in blood combined with a short gluten challenge. Details about the amount and type of gluten antigen and the starting material are included, as well as the strategy to easily characterize and identify the cells of interest using flow cytometry. This methodology constitutes a diagnostic tool for CD diagnosis of high specificity and sensitivity for seropositive disease (>95%) as an alternative to long-term gluten challenge and open new possibilities to test the response to gluten in research and clinical trials.

Different Gene Expression Signatures in Children and Adults with Celiac Disease.

Celiac disease (CD) is developed after gluten ingestion in genetically susceptible individuals. It can appear at any time in life, but some differences are commonly observed between individuals with onset early in life or in adulthood. We aimed to investigate the molecular basis underlying those differences. We collected 19 duodenal biopsies of children and adults with CD and compared the expression of 38 selected genes between each other and with the observed in 13 non-CD controls matched by age. A Bayesian methodology was used to analyze the differences of gene expression between groups. We found seven genes with a similarly altered expression in children and adults with CD when compared to controls (C2orf74, CCR6, FASLG, JAK2, IL23A, TAGAP and UBE2L3). Differences were observed in 13 genes: six genes being altered only in adults (IL1RL1, CD28, STAT3, TMEM187, VAMP3 and ZFP36L1) and two only in children (TNFSF18 and ICOSLG); and four genes showing a significantly higher alteration in adults (CCR4, IL6, IL18RAP and PLEK) and one in children (C1orf106). This is the first extensive study comparing gene expression in children and adults with CD. Differences in the expression level of several genes were found between groups, being notorious the higher alteration observed in adults. Further research is needed to evaluate the possible genetic influence underlying these changes and the specific functional consequences of the reported differences.

Tratamiento de inducción y mantenimiento con adalimumab en la enfermedad de Crohn: un estudio abierto / No disponible

Introducción: el adalimumab ha demostrado, en ensayos clínicoscontrolados con placebo y en estudios no controlados, serefectivo en la EC luminal y fistulosa perianal.Objetivo: evaluar la eficacia y seguridad del adalimumabcomo tratamiento de inducción y mantenimiento en la EC.Metodología: se incluyeron 22 pacientes con EC tratadoscon adalimumab (16 por enfermedad luminal y 6 por enfermedadfistulosa perianal activa). Veintiún pacientes habían recibido previamenteIFX. Se realizó tratamiento de inducción con 160 mgs.c. en la semana 0 y 80 mg s.c. a las 2 semanas. Los respondedoresrecibieron 40 mg s.c. cada 14 días como tratamiento demantenimiento. Se valoró la respuesta a las 4 semanas de la dosisinicial, y se clasificó la respuesta como remisión, respuesta parcialo ausencia de respuesta.Resultados: tras la inducción, el 25% de los pacientes conenfermedad luminal tuvieron remisión completa y el 56,3% respuestaparcial. La respuesta clínica se mantuvo al año en el71,6% de los pacientes, a los 18 meses en el 53,7% y a los 48meses en el 35,8%. No se objetivaron diferencias en la respuestaentre pacientes que presentaron reacciones de hipersensibilidad opérdida de respuesta a IFX.Todos los pacientes con enfermedad fistulosa perianal (n = 6) habíanrecibido previamente tratamiento con IFX. Tras la inducción un16,7% entran en remisión y un 66,7% presentan respuesta parcial.Todos los pacientes mantienen remisión o respuesta en el tiempocon una mediana de seguimiento de 15 meses.Conclusiones: el adalimumab es un tratamiento eficaz y seguroen la inducción y mantenimiento de la respuesta en la EC luminaly fistulosa perianal. Estos resultados confirman que los hallazgosobtenidos en los ensayos clínicos controlados sonreproducibles en la práctica clínica diaria

Background: adalimumab has been shown in placebo-controlledclinical trials and uncontrolled studies to be effective in luminaland perianal fistulizing CD.Objective: to evaluate the efficacy and safety of adalimumabfor induction and maintenance therapy in CD.Methods: twenty-two patients with CD treated with adalimumab(16 for luminal disease and 6 for active perianal fistulizingdisease) were included. Twenty-one patients had previously receivedIFX. All patients received induction therapy with 160 mgs.c. at week 0, and 80 mg s.c. at week 2. Responders receivedmaintenance therapy with 40 mg s.c. every 14 days. Responsewas assessed at 4 weeks after the initial dose, and classified as remission,partial response, or non-response.Results: after induction, 25% of patients with luminal diseasehad a complete remission, and 56.3% had a partial response.Clinical response was maintained in 71.6% of patients at 1 year,in 53.7% at 18 months, and in 35.8% at 48 months. No differencesin response were observed between patients with hypersensitivityreactions or loss of response to IFX.All patients with perianal fistulizing disease (n = 6) had beenpreviously treated with IFX. After induction 16.7% entered remission,and 66.7% had a partial response. All patients maintainedremission or response over time, with a median follow-up of 15months.Conclusions: adalimumab is an effective and safe treatmentfor the induction and maintenance of response in luminal and perianalfistulizing CD. These results confirm that the findings obtainedin controlled clinical trials are reproducible in clinical practice

[Adalimumab induction and maintenance therapy for Crohn's disease. An open-label study]. / Tratamiento de induccion y mantenimiento con adalimumab en la enfermedad de Crohn: un estudio abierto.

BACKGROUND: adalimumab has been shown in placebo-controlled clinical trials and uncontrolled studies to be effective in luminal and perianal fistulizing CD. OBJECTIVE: to evaluate the efficacy and safety of adalimumab for induction and maintenance therapy in CD. METHODS: twenty-two patients with CD treated with adalimumab (16 for luminal disease and 6 for active perianal fistulizing disease) were included. Twenty-one patients had previously received IFX. All patients received induction therapy with 160 mg s.c. at week 0, and 80 mg s.c. at week 2. Responders received maintenance therapy with 40 mg s.c. every 14 days. Response was assessed at 4 weeks after the initial dose, and classified as remission, partial response, or non-response. RESULTS: after induction, 25% of patients with luminal disease had a complete remission, and 56.3% had a partial response. Clinical response was maintained in 71.6% of patients at 1 year, in 53.7% at 18 months, and in 35.8% at 48 months. No differences in response were observed between patients with hypersensitivity reactions or loss of response to IFX.All patients with perianal fistulizing disease (n = 6) had been previously treated with IFX. After induction 16.7% entered remission, and 66.7% had a partial response. All patients maintained remission or response over time, with a median follow-up of 15 months. CONCLUSIONS: adalimumab is an effective and safe treatment for the induction and maintenance of response in luminal and perianal fistulizing CD. These results confirm that the findings obtained in controlled clinical trials are reproducible in clinical practice.