Cytotoxic T Lymphocyte Antigen 4 Haploinsufficiency Presenting As Refractory Celiac-Like Disease: Case Report

Primary immunodeficiency may present with treatment-refractory enteropathy. We present two patients with celiac/celiac-like disease diagnosed in early childhood and refractory to the gluten-free diet. One patient had features of multi-system autoimmunity, whereas the other had celiac-like disease as an isolated clinical finding. Both patients underwent genetic testing given disease refractoriness and were ultimately diagnosed with cytotoxic T lymphocyte antigen 4 (CTLA4) haploinsufficiency. They are both now in complete clinical and endoscopic remission on abatacept. CTLA4 haploinsufficiency has incomplete penetrance and significant phenotypic heterogeneity but should be considered in the differential diagnosis of refractory celiac/celiac-like disease, as treatment implications are significant

Beyond the Workshop: Results From a Longitudinal, Interprofessional Teaching Certificate Program

OBJECTIVES While most hospital-based, healthcare professionals are expected to teach and supervise, few receive training in education. We designed, implemented, and evaluated an interprofessional, hospital-based teaching certificate program based on experiential learning and reflective practice for healthcare professionals with little or no formal training in education. METHODS Participants attended educational seminars; incorporated new concepts, skills, and behaviors in their teaching; and submitted written reflections. Participants also met with an education coach, received feedback from a trained observer, and observed a “master teacher.” We used descriptive statistics to analyze a survey distributed to the 2017–2019 cohort. We also analyzed written reflections to determine whether participants described a new teaching skill, concept, or behavior, and how they applied these to their teaching. RESULTS Survey completion rate was 15/20 (75%). Participants described feeling connected to an educator community, establishing educational alliances with senior educators, and learning teaching strategies from other certificate members outside their own profession. Participants indicated they are more likely to pursue educational innovation, leadership, and scholarship. In the reflections, 88% described incorporating a new concept in their teaching. CONCLUSION Participants in an interprofessional teaching certificate program engaged in a curriculum of professional development in education. Graduates of the program reported knowledge gain, behavior change, and establishment of educational alliances and a community of practice

Desquamative enteropathy and pyloric atresia without skin disease caused by a novel intracellular beta4 integrin mutation

ITGB4 mutation may induce a desquamative enteropathy in infancy without significant skin disease. A history of pyloric atresia is important in infants with severe chronic diarrhoeal disease and should prompt investigation for JEB-PA associated mutations. Acquired immune responses may exacerbate primary genetic disorders of epithelial adhesion and immunomodulatory therapy may be beneficial

Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4–insufficient subjects

BACKGROUND: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a negative immune regulator. Heterozygous CTLA4 germline mutations can cause a complex immune dysregulation syndrome in human subjects. OBJECTIVE: We sought to characterize the penetrance, clinical features, and best treatment options in 133 CTLA4 mutation carriers. METHODS: Genetics, clinical features, laboratory values, and outcomes of treatment options were assessed in a worldwide cohort of CTLA4 mutation carriers. RESULTS: We identified 133 subjects from 54 unrelated families carrying 45 different heterozygous CTLA4 mutations, including 28 previously undescribed mutations. Ninety mutation carriers were considered affected, suggesting a clinical penetrance of at least 67%; median age of onset was 11 years, and the mortality rate within affected mutation carriers was 16% (n = 15). Main clinical manifestations included hypogammaglobulinemia (84%), lymphoproliferation (73%), autoimmune cytopenia (62%), and respiratory (68%), gastrointestinal (59%), or neurological features (29%). Eight affected mutation carriers had lymphoma, and 3 had gastric cancer. An EBV association was found in 6 patients with malignancies. CTLA4 mutations were associated with lymphopenia and decreased T-, B-, and natural killer (NK) cell counts. Successful targeted therapies included application of CTLA-4 fusion proteins, mechanistic target of rapamycin inhibitors, and hematopoietic stem cell transplantation. EBV reactivation occurred in 2 affected mutation carriers after immunosuppression. CONCLUSIONS: Affected mutation carriers with CTLA-4 insufficiency can present in any medical specialty. Family members should be counseled because disease manifestation can occur as late as 50 years of age. EBV- and cytomegalovirus-associated complications must be closely monitored. Treatment interventions should be coordinated in clinical trials