Luciana Guzmán’s research while affiliated with Sister María Ludovica Children's Hospital and other places

Objectives Diagnosis of celiac disease (CeD), an immune-mediated disorder, is based on clinical presentation, a panel of serological markers, and the histopathological findings in duodenal biopsies. Commonly, pediatric CeD patients fulfill these criteria for diagnosis. However, lack of correlation between serology tests and histology, or no accessible biopsies because of clinical conditions or during the COVID pandemic, are conditions that led to inconclusive diagnoses. Since the majority of CeD patients carry HLA-DQ2 and/or DQ8 alleles, HLA testing is used as a complementary tool in diagnosis though is costly and not broadly available for gastroenterology centers. Methods We performed a retrospective study to assess the performance of HLA testing when applied to selected groups of patients who could not be definitely diagnosed following the common algorithm. Eighty patients underwent testing for CeD-related HLA-DQ2 and DQ8 alleles. Results HLA typing contributed to diagnosis in 34 patients with positive serology but normal mucosa or those who presented negative serology or slightly positive serology (less than 3 times ULN) and duodenal histopathological changes. In patients with normal histology and negative or slightly positive serology, or those who did not undergo intestinal biopsy (39 in total), HLA typing contributed to CeD diagnosis in 23 cases, only 16 patients were admitted for a clinical follow-up program. Conclusion HLA-DQ typing supported the diagnosis in 57 of 80 children (71.2%) with previously inconclusive results, providing a beneficial approach for diagnosing celiac disease (CeD) in selected cases.

The goal of the treatment is to relieve symptoms, achieve duodenal mucosal healing, avoid long term complications, and ensure children´s appropriate growth, for which it´s necessary to follow a lifelong, nutritionally complete and healthy gluten free diet (GFD). The Celiac Disease Working Group of the Gastroenterology Committee of the Sociedad Argentina de Pediatría developed this guide based on expert consensus, aimed at gastroenterologists, pediatricians and primary care physicians with the objective of updating the following topics: Treatment. Definition of gluten free food. Nutritional approach to children with celiac disease. Clinical, nutritional aspects and laboratory tests that should be monitored at initial controls. The importance of follow up visits, their frequency, which professionals should make up the monitoring team and what should be assessed. How to assess adherence to the GFD and other recommendations.

Los trastornos del espectro autista comprenden alteraciones centrales del desarrollo neurológico que incluyen déficit en las interacciones sociales y la comunicación, conductas repetitivas y trastornos sensoriales. Existe un aumento de la frecuencia de trastornos gastrointestinales en los niños con trastornos del espectro autista en comparación con la población de niños neurotípicos. Los factores implicados en este aumento de frecuencia son múltiples, encontrando entre ellos factores genéticos, desequilibrio de la microbiota intestinal, disfunción del sistema inmunológico. Los trastornos gastrointestinales observados con mayor frecuencia en estos pacientes son estreñimiento, dolor abdominal, náuseas y vómitos, problemas de selectividad o alergia alimentaria, distensión abdominal, flatulencias, aerofagia, diarrea, incontinencia fecal y enuresis. Los niños con trastornos del espectro autista suelen tener hábitos alimentarios selectivos y limitados. En consecuencia, tienen dietas desequilibradas que carecen de nutrientes esenciales y, a su vez, esto contribuye a la aparición de trastornos gastrointestinales. Además, a menudo presentan alteraciones en el procesamiento sensorial que afectan la percepción de los síntomas o las señales digestivas. Conocer y tratar los trastornos gastrointestinales en los niños con trastornos del espectro autista puede ser un desafío. Requieren una evaluación integral por un equipo multidisciplinario que cuente con pediatras, gastroenterólogos, psicólogos, nutricionistas, terapeutas ocupacionales, acompañantes terapéuticos, neurólogos y docentes. Aliviar los síntomas gastrointestinales de los pacientes con trastornos del espectro autista puede mejorar sus patrones de sueño, apetito y alimentación, aumentar sus niveles de energía y contribuir a una sensación general de bienestar. Esto mejora el comportamiento, la función cognitiva y las habilidades educativas.

Celiac disease (CD) is an immune-driven disease characterized by tissue damage in the small intestine of genetically-susceptible individuals. We evaluated here a crucial immune regulatory pathway involving TYRO3, AXL, and MERTK (TAM) receptors and their ligands PROS1 and GAS6 in duodenal biopsies of controls and CD patients. We found increased GAS6 expression associated with downregulation of PROS1 and variable TAM receptors levels in duodenum tissue of CD patients. Interestingly, CD3+ lymphocytes, CD68+, CD11c+ myeloid and epithelial cells, showed differential expressions of TAM components comparing CD vs controls. Principal component analysis revealed a clear segregation of two groups of CD patients based on TAM components and IFN signaling. In vitro validation demonstrated that monocytes, T lymphocytes and epithelial cells upregulated TAM components in response to IFN stimulation. Our findings highlight a dysregulated TAM axis in CD related to IFN signaling and contribute to a deeper understanding of the pathophysiology of CD.

RESUMEN El objetivo del tratamiento de la enfermedad celíaca en los niños es aliviar los síntomas, lograr la curación de la mucosa duodenal, evitar las complicaciones a largo plazo y asegurar el crecimiento adecuado durante la niñez y adolescencia, para lo cual es necesario adherir a una dieta libre de gluten nutricionalmente completa, saludable y de por vida. El Grupo de Trabajo en Enfermedad Celíaca del Comité de Gastroenterología de Sociedad Argentina de Pediatría elaboró esta guía sobre la base de consenso de expertos, orientado a gastroenterólogos, pediatras y médicos de atención primaria con el objetivo de realizar una actualización de los siguientes tópicos: tratamiento; definición de alimentos libres de gluten; abordaje nutricional al momento del diagnóstico; controles iniciales sobre aspectos clínicos, nutricionales y de laboratorio. Destacar la importancia del seguimiento, cómo debe conformarse el equipo de control y frecuencia de los mismos. Cómo se debe evaluar la adherencia a la dieta libre de gluten y otras recomendaciones. Palabras clave: enfermedad celíaca; pediatría. ABSTRACT The goal of the treatment is to relieve symptoms, achieve duodenal mucosal healing, avoid long term complications, and ensure children´s appropriate growth, for which it´s necessary to follow a lifelong, nutritionally complete and healthy gluten free diet (GFD). The Celiac Disease Working Group of the Gastroenterology Committee of the Sociedad Argentina de Pediatría developed this guide based on expert consensus, aimed at gastroenterologists, pediatricians and primary care physicians with the objective of updating the following topics: Treatment. Definition of gluten free food. Nutritional approach to children with celiac disease. Clinical, nutritional aspects and laboratory tests that should be monitored at initial controls. The importance of follow up visits, their frequency, which professionals should make up the monitoring team and what should be assessed. How to assess adherence to the GFD and other recommendations.

Background: Conventional therapy can result in remission in mild-moderate pediatric Crohn's disease (CD). However, some patients experience loss of response to biological drugs despite increased dosage. Methods: We planned to determine that CD exclusion diet plus partial enteral nutrition offers additional benefits in asymptomatic children with CD having elevated fecal calprotectin. A randomized, open-label, pilot, controlled interventional study was conducted in children with CD while on medical treatment and elevated fecal calprotectin on routine testing. Patients continued their medications and were randomized into a group that received CD exclusion diet plus partial enteral nutrition for 12 weeks and one that continued a regular diet. Results: Twenty-one patients participated: 11 received CD exclusion diet plus partial enteral nutrition and 10, regular diet. Median fecal calprotectin in the CD exclusion diet plus partial enteral nutrition decreased in 9/11 to 50% of baseline, remaining practically unchanged in the regular diet, except for two patients (p = 0.005). Body mass index z-score increased in the CD exclusion diet plus partial enteral nutrition. Only 1/11 patients in the CD exclusion diet plus partial enteral nutrition group, while 4/10 in the regular diet, experienced clinical relapse (p = 0.149). Only one patient in the CD exclusion diet plus partial enteral nutrition, while eight in the regular diet, were considered to need their biologic treatment intensified (p = 0.005); 2/11 in the CD exclusion diet plus partial enteral nutrition had the dose or frequency of the biologic reduced vs. none (0/10) in the regular diet group. The short Pediatric Crohn's Disease Activity Index and anthropometry showed no significant changes in either group. Conclusions: Diet therapy could be a useful addition to medications in children with CD in apparent remission, but elevated fecal calprotectin. Trial registration: Clinical trial number: NCT05034458.

Food allergies have become a health concern worldwide. Around 6-10% of children are allergic to cow´s milk proteins. We have previously characterized colorectal polyps in patients sensitized to food allergens. These polyps are classified as inflammatory and present a Th2 environment, with elevated IL-13 and IL-4 and are a site of IgE synthesis. In this study, we characterized and isolated cow´s milk protein-specific T cell lines and T cell clones from the lamina propria of polyps from patients sensitized to these proteins. Isolated T cells responded to cow´s milk proteins similarly to peripheral blood T cells, showing antigen-specific cell proliferation and Th2 cytokines release in vitro. T cell clones obtained were all CD4+ T cells and expressed the membrane TCRαβ receptor and secreted higher IL-4, IL-5 and IL-13 amounts than unstimulated cells, whereas IFN-γ secretion remained unchanged. Remarkably, the gut homing chemokine receptor CCR9 was augmented in cow’s milk-specific peripheral and lamina propria T cells, and CCL25 was found to be expressed in the inflammatory polyp tissue and not in the adjacent mucosa. In conclusion, we isolated and characterized cow´s milk-specific lamina propria CD4+ Th2 cells from colonic inflammatory polyps. CCR9 expression on these cells, along with increase secretion of CCL25 in the polyp, favor recruitment and cow’s milk specific allergic response within the inflammatory polyp tissue. Our findings may be critical to understand the underlying mechanism that promotes IgE synthesis in the colon of cow´s milk proteins allergic patients, contributing to the development of novel T cell-targeted immunotherapies.