In vitro allergen-specific immunoglobulin E (IgE) detection and quantification tests are routinely performed in clinical laboratories to diagnose patients with a suspected allergy. Numerous commercial assays are available to test for allergies, but the results can vary widely, thereby influencing both diagnosis and treatment. Given the challenges posed by differences in the various assays for in vitro determination of specific IgE, a group of experts has compiled in a document a series of recommendations on the implications that the use of a certain in vitro technique may have and the impact on the management of the allergic patient that the differences between the various techniques represent. The reading and analysis of this consensus document will help to understand the implications of the change of in vitro diagnostic method in the management of the patient with allergy, in the quality of life and in the socioeconomic costs associated with the disease.
SASH3 is a lymphoid-specific adaptor protein. In a recent study, SASH3 deficiency was described as a novel X-linked combined immunodeficiency with immune dysregulation, associated with impaired TCR signaling and thymocyte survival in humans. The small number of patients reported to date showed recurrent sinopulmonary, cutaneous and mucosal infections, and autoimmune cytopenia. Here we describe an adult patient previously diagnosed with common variable immunodeficiency (CVID) due to low IgG and IgM levels and recurrent upper tract infections. Two separate, severe viral infections drew our attention and pointed to an underlying T cell defect: severe varicella zoster virus (VZV) infection at the age of 4 years and bilateral pneumonia due type A influenza infection at the age of 38. Genetic testing using an NGS-based custom-targeted gene panel revealed a novel hemizygous loss-of-function variant in the SASH3 gene (c.505C>T/p.Gln169*). The patient’s immunological phenotype included marked B cell lymphopenia with reduced pre-switch and switch memory B cells, decreased CD4+ and CD8+ naïve T cells, elevated CD4+ and CD8+ TEMRA cells, and abnormal T cell activation and proliferation. The patient showed a suboptimal response to Streptococcus pneumoniae (polysaccharide) vaccine, and a normal response to Haemophilus influenzae type B (conjugate) vaccine and SARS-CoV-2 (RNA) vaccine. In summary, our patient has a combined immunodeficiency, although he presented with a phenotype resembling CVID. Two severe episodes of viral infection alerted us to a possible T-cell defect, and genetic testing led to SASH3 deficiency. Our patient displays a milder phenotype than has been reported previously in these patients, thus expanding the clinical spectrum of this recently identified inborn error of immunity.
ResumenEn la evaluación del paciente con sospecha de alergia las pruebas de detección y cuantificación de la inmunoglobulina E (IgE) específica in vitro se usan de manera habitual en los laboratorios clínicos para ayudar en el diagnóstico de la alergia. Actualmente existen diferentes alternativas comerciales para realizar estos ensayos, pero los resultados obtenidos por cada uno de ellos pueden variar, lo que condiciona el diagnóstico y el tratamiento que se le proporcionará al paciente. Con el fin de dar respuesta a los retos planteados por las diferencias entre las distintas técnicas para la determinación in vitro de la IgE específica, un grupo de expertos ha recogido en un documento una serie de recomendaciones sobre las implicaciones que puede tener el uso de una determinada técnica in vitro y el impacto en el manejo del paciente alérgico que suponen las diferencias entre las distintas técnicas. La lectura y el análisis de este documento de consenso ayudarán a entender las implicaciones que tiene el cambio de método de diagnóstico in vitro en el manejo del paciente con alergia, en su calidad de vida y en los costes socioeconómicos asociados a la enfermedad.
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