The Role of Sphingolipids in Allergic Disorders

12 Pág.Allergy is defined as a complex chronic inflammatory condition in which genetic and environmental factors are implicated. Sphingolipids are involved in multiple biological functions, from cell membrane components to critical signaling molecules. To date, sphingolipids have been studied in different human pathologies such as neurological disorders, cancer, autoimmunity, and infections. Sphingolipid metabolites, in particular, ceramide and sphingosine-1-phosphate (S1P), regulate a diverse range of cellular processes that are important in immunity and inflammation. Moreover, variations in the sphingolipid concentrations have been strongly associated with allergic diseases. This review will focus on the role of sphingolipids in the development of allergic sensitization and allergic inflammation through the activation of immune cells resident in tissues, as well as their role in barrier remodeling and anaphylaxis. The knowledge gained in this emerging field will help to develop new therapeutic options for allergic disorders.This research was funded by the Spanish Government (MINECO, grant BIO2017-84548- R); by Instituto de Salud Carlos III (ISCIII) (PI19/00044); by ISCIII co-founded by FEDER Thematic Networks and Cooperative Research Centres: ARADYAL (RD16/0006/0003; RD16/0006/0015); and by Community of Madrid (FOODAL-CM_S2018/BAAA-4574). JT-A was funded by Instituto de Salud Carlos III (ISCIII), co-founded by FEDER Thematic Networks and Cooperative Research Centres: ARADYAL (RD16/0006/0003).Peer reviewe

Unraveling the Diagnosis of Kiwifruit Allergy: Usefulness of Current Diagnostic Tests

Objectives: To determine the usefulness of the in vitro and in vivo methods used in the diagnosis of kiwifruit allergy and to specifically assess the impact of seed proteins on sensitivity. Methods: We performed skin prick tests (SPTs) using various commercial extracts, homemade pulp, and seed extracts and prick-prick tests with kiwifruit on 36 allergic patients. The presence of specific IgE (sIgE) was assessed using the ImmunoCAP (kiwifruit extract), ELISA (Act d 1, Act d 2), ISAC, and FABER assays. Immunoblotting of seed extract was carried out, and a single-blind oral food challenge was performed with whole seeds in seed-sensitized individuals. Results: The prick prick test with kiwifruit demonstrated the highest diagnostic capacity (81.8% sensitivity and 94.1% specificity) among the in vivo tests. The sIgE levels measured using ImmunoCAP (kiwifruit extract) showed a similar sensitivity to that of global ISAC and FABER (63.9%, 59.5%, and 58.3%, respectively). Act d 1 was the major allergen. Sensitization to Act d 1 was associated with positive sIgE results to whole kiwifruit extract detected by ImmunoCAP (P<.000). A positive SPT result to kiwifruit seeds was associated with severe symptoms induced by kiwifruit (P=.019) as a marker of advanced disease, but not with clinically relevant sensitization. Challenge testing with kiwifruit seeds performed on 8 seed-sensitized patients yielded negative results. Conclusions: Sensitization to Act d 1 is associated with a positive result in conventional diagnostic techniques, whereas kiwifruit seed sensitization does not increase the sensitivity of the diagnostic techniques evaluated.Objetivos: Determinar la rentabilidad diagnóstica de las técnicas in vitro e in vivo utilizadas en el diagnóstico de alergia al kiwi y estudiar la influencia de las proteínas alergénicas de las semillas en su sensibilidad. Métodos: Se seleccionaron 36 pacientes alérgicos a kiwi. Se les realizó prick test con cuatro extractos comerciales diferentes y prick-prick con kiwi. Se determinó IgE específica mediante ImmunoCAP (extracto de kiwi), ELISA (Act d 1, Act d 2), las micromatrices ISAC y FABER e Immunoblotting de extracto de semilla de kiwi. Se realizó exposición oral simple ciego frente a semilla de kiwi en pacientes sensibilizados a la semilla. Resultados: El prick-prick de kiwi fue la prueba in vivo con mayor rendimiento (sensibilidad 81,8%, especificidad 94,1%). El ImmunoCAP de extracto de kiwi mostró una sensibilidad similar a la global del ISAC y del FABER (63,9%, 59,5% y 58,3%, respectivamente). Act d 1 fue el alérgeno mayoritario. Se encontró asociación entre los niveles de IgE específica frente a Act d 1 (ISAC) y el extracto de kiwi mediante ImmunoCAP (p <0,000). La prueba cutánea positiva con semilla se asoció con mayor gravedad de síntomas frente a kiwi (p = 0,019), como marcador de enfermedad avanzada, pero no como sensibilización clínicamente relevante. La prueba de provocación con semillas fue negativa en los ocho pacientes provocados. Conclusiones: La sensibilización a Act d 1 se asocia con resultados positivos con las técnicas diagnósticas convencionales. La sensibilización frente a semillas no mejora el rendimiento de las técnicas evaluadas