not-yet-known not-yet-known not-yet-known unknown Abstract Background: Peanut allergy (PA) is a significant health concern. Children with a relatively low reaction threshold PA have an increased risk of accidental life-threatening reactions, compared to those with a higher threshold. Diagnostic and treatment protocols for high threshold PA are also safer and easier to implement. Our study aims to identify clinical factors determining the reaction threshold in PA children. Methods: A retrospective study, collecting and analyzing data of challenge-proven PA children under 12 years of age, from our pediatric food allergy center, where all children with suspected PA are offered a diagnostic challenge. The data included demographics, medical history, skin test and oral food challenge results. Results: A total of 202 children under 12 years of age (mean 42 months, 95% CI 38-46) with challenge-proven PA were enrolled in the study. Children with low threshold PA (threshold less than 100mg) were more likely to be older than 4 years (43.6% Vs 21.7%, p < 0.001). In a gender subanalysis we found girls had additional influencing factors such as previous systemic/anaphylactic reaction (p<0.001). In a decision tree analysis, the major modifiable risk factor was a diagnosis at a young age. Conclusion: Since an oral food challenge is the gold standard for the diagnosis of PA, performing a diagnostic challenge at a young age, optimizes our chance to diagnose PA with a relatively high threshold, increasing the safety and outcomes of potential interventions. Therefore, the early referral of young patients for a diagnostic workup is mandated.

Background: During the process of generating diverse T and B cell receptor (TCR and BCR, respectively) repertoires, double strand DNA breaks are produced. Subsequently, these breaks are corrected by a complexed system led mainly by the non-homologous end-joining (NHEJ). Mutations in proteins involved in this process, including the XLF/ Cernunnos gene, cause severe combined immunodeficiency syndrome (SCID) along with neurodevelopmental disease and susseptability to inoizing radiation. Objective: To provide new clinical and immunological insights on XLF/Cernunnos deficiency, arising from a newly diagnosed patient with severe immunodeficiency. Methods: A male infant, born to consanguineous parents, suspected of having primary immunodeficiency underwent immunological and genetic work up. This included a thorough assessment of T cell phenotyping and lymphocyte activation by mitogen stimulation tests, whole exome sequencing (WES), TCR repertoire Vβ repertoire via flow cytometry analysis and TCR and BCR via next generation sequencing (NGS). Results: Clinical findings included microcephaly, recurrent bacterial viral pneumonia and failure to thrive. Immune workup revealed lymphopenia, reduced T cell function and hypogammaglubolinemia. A skewed TCR Vβ repertoire, TCR gamma (TRG) repertoire and BCR repertoire were determined in the patient. Genetic analysis identified a novel autosomal recessive homozygous missense mutation in XLF/Cernunnos c. A580Ins.T; p. M194fs. The patient underwent a successful hematopoietic stem cell transplantation (HSCT). Conclusions: A novel XLF/Cernunnos mutation is reported in a patient presented with SCID phenotype that displayed clonally expanded T and B cells. An adjusted HSCT was safe to ensure full T cell immune reconstitution.