Mónica Piquer

Baseline specific IgE levels are useful to predict safety of oral immunotherapy in egg-allergic children.

Oral immunotherapy (OIT) is a promising treatment for food allergy but dose‐related reactions are common.

Tolerance to egg proteins in egg‐sensitized infants without previous consumption

Egg‐sensitized infants who have never eaten egg may react at first ingestion. We sought to determine the association between skin prick test (SPT) and specific IgE (sIgE) to egg proteins (EP) and oral food challenge (OFC) outcomes to find cut‐off points which can diagnose egg allergy.

Food protein–induced enterocolitis syndrome to fish and egg usually resolves by age 5 years in Spanish children

Food proteineinduced enterocolitis syndrome to fish and egg usually resolves by age 5 years in Spanish children Marta Vazquez-Ortiz, MD, PhD*, Adrianna Machinena, MD*, Olga Dominguez, MD, Montserrat Alvaro, MD, PhD, Katty Calvo-Campoverde, MD, María Teresa Giner, MD, Rosa Jiménez-Feijoo, MD, PhD, Jaime Lozano, MD, Mònica Piquer, MD, Marcia Dias, MD, María del Mar Folqué, MD, and Ana María Plaza, MD, PhD

Evaluating the Genetics of Common Variable Immunodeficiency: Monogenetic Model and Beyond

Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency characterized by recurrent infections, hypogammaglobulinemia and poor response to vaccines. Its diagnosis is made based on clinical and immunological criteria, after exclusion of other diseases that can cause similar phenotypes. Currently, less than 20% of cases of CVID have a known underlying genetic cause. We have analyzed whole-exome sequencing and copy number variants data of 36 children and adolescents diagnosed with CVID and healthy relatives to estimate the proportion of monogenic cases. We have replicated an association of CVID to p.C104R in TNFRSF13B and reported the second case of homozygous patient to date. Our results also identify five causative genetic variants in LRBA, CTLA4, NFKB1, and PIK3R1, as well as other very likely causative variants in PRKCD, MAPK8, or DOCK8 among others. We experimentally validate the effect of the LRBA stop-gain mutation which abolishes protein production and downregulates the expression of CTLA4, and of the frameshift indel in CTLA4 producing expression downregulation of the protein. Our results indicate a monogenic origin of at least 15–24% of the CVID cases included in the study. The proportion of monogenic patients seems to be lower in CVID than in other PID that have also been analyzed by whole exome or targeted gene panels sequencing. Regardless of the exact proportion of CVID monogenic cases, other genetic models have to be considered for CVID. We propose that because of its prevalence and other features as intermediate penetrancies and phenotypic variation within families, CVID could fit with other more complex genetic scenarios. In particular, in this work, we explore the possibility of CVID being originated by an oligogenic model with the presence of heterozygous mutations in interacting proteins or by the accumulation of detrimental variants in particular immunological pathways, as well as perform association tests to detect association with rare genetic functional variation in the CVID cohort compared to healthy controls.

Usefulness of the ratio total IgE / specific IgE (sIgE) to predict tolerance in children allergic to cow's milk proteins (CMP)

Background Cow’s milk (CM) IgE-mediated allergy is the most common food allergy in children. It affects 2 - 3% of the general population. About 80% of children allergic to CMP reach natural tolerance in the third year of life. It remains difficult to decide when it is time to attempt a controlled food challenge (CFC) to reintroduce CM in their diets. Objectives. To evaluate if the ratio total IgE / CM sIgE or total IgE / casein sIgE can be more useful than the single measurement of sIgE to predict tolerance in our patients, and to determine the highest sensitivity cut-off point. Methods Retrospective, observational study. The medical records of 178 patients allergic to CM with CFC performed between January 2010 and December 2011 were reviewed. Clinical data, skin prick tests (SPT), total IgE, CM sIgE and casein sIgE at baseline and at the time of the CFC were recorded. These measures were compared between groups of tolerant and nontolerant patients using the nonparametric Mann-Whitney. ROC curves were performed to evaluate predictive values of tolerance for total IgE, CM sIgE, casein sIgE and ratios (total IgE / CM sIgE; total IgE / casein sIgE).