Artemis deficiency: A large cohort including a novel variant with increased radiosensitivity.

BACKGROUND: Artemis deficiency is an autosomal recessive disorder characterized by a combined immunodeficiency with increased cellular radiosensitivity. In this review, the clinical and genetic characteristics of 15 patients with DCLRE1C variants are presented. METHODS: The demographic, clinical, immunologic, and genetic characteristics of patients with confirmed DCLRE1C variants diagnosed between 2013 and 2023 were collected retrospectively. Three patients were evaluated for radiosensitivity by the Comet assay, compared with age- and sex-matched healthy control. RESULTS: Seven patients who had severe infections in the first 6 months of life were diagnosed with T-B-NK+ SCID (severe combined immunodeficiency). Among them, four individuals underwent transplantation, and one of those died due to post-transplant complications in early life. Eight patients had hypomorphic variants. Half of them were awaiting a suitable donor, while the other half had already undergone transplantation. The majority of patients were born into a consanguineous family (93.3%). Most patients had recurrent sinopulmonary infections (73.3%), and one patient had no other infection than an acute respiratory infection before diagnosis. Two patients (13.3%) had autoimmunity in the form of autoimmune hemolytic anemia. Growth retardation was observed in only one patient (6.6%), and no malignancy was detected in the surviving 11 patients during the median (IQR) of 21.5 (12-45) months of follow-up. Three patients who had novel variants exhibited increased radiosensitivity and compromised DNA repair, providing a potential vulnerability to malignant transformation. CONCLUSION: Early diagnosis, radiation avoidance, and careful preparation for transplantation contribute to minimizing complications, enhancing life expectancy, and improving the patient's quality of life.

The Evaluation of pediatric patients with suspected polyethylene glycol and polysorbate allergy before mRNA SARS-CoV2 vaccination

mRNA vaccines, particularly, have been associated with an increased risk of allergic reactions and rarely anaphylaxis. Although rare, vaccine reactions can cause significant anxiety and fear in the population, leading to indecision and vaccine refusal. This study aimed to retrospectively evaluate the role of polyethylene glycol (PEG) sensitivity in vaccination decision-making in pediatric patients at high risk of allergy or with suspected allergic reactions to the first dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccine. Seventeen enrolled patients were found to have decreased readiness to receive the Coronavirus Disease 2019 (COVID-19) vaccine after developing hypersensitivity to multiple and/or injectable drugs. Skin testing was performed. A basophil activation test with PEG-2000 and 4000 was performed on three patients who were ineligible for skin prick tests. Nine patients with negative tests received the vaccine without complications. One patient had urticarial angioedema despite negative tests. Three patients with positive tests did not agree to desensitization with the mRNA vaccine, and one of them was vaccinated with the inactivated COVID-19 vaccine. Four patients recurred despite negative tests. The general recommendation for patients describing severe reactions to drugs, foods, and allergens, such as toxins that do not contain the adjuvants of the SARS-CoV-2 vaccines, is to be routinely vaccinated with safety precautions. Excipients such as PEG and polysorbate-80 used in COVID-19 vaccines could be potential allergens, but this hypothesis is unclear. The predictive values of these adjuvants for skin testing and in vitro testing are controversial. Further research is needed on the hypersensitivity reactions of adjuvants, the predictive values of skin tests, and etiopathogenesis (AU)