Allergic responses are mainly caused by IgE, which is often located on the cell surface. The current diagnostic method detects both allergen-specific IgE and total IgE levels, but a number of allergic patients have a normal serum IgE level, which is a poor clinical correlate for allergy. Here, we developed a simple method to detect the level of cell-bound IgE by dissociating it from blood cells with lactic acid. Dissociated cell-bound IgE and plasma IgE levels were detected using the same ELISA kit at the same time. We established two clinical cohorts: an allergic patient group and a healthy participant group. In general, cell-bound IgE correlated well with plasma IgE; however, some patients exhibited high cellbound IgE levels but low plasma IgE levels. We recommended 350 ng/mL peripheral blood total IgE (cell-bound ige + plasma IgE) as the cut-off value for allergy diagnosis. Using this indicator, 90.32% of our allergic patients were correctly diagnosed. The peripheral blood total IgE level is a promising clinical diagnostic indicator in allergic patients and will provide more guidance for allergy diagnosis and therapeutic evaluation.Immunoglobulin E (IgE) plays a key role in the development of allergic diseases 1,2 , and it is necessary to detect the IgE level for diagnosis and treatment evaluation 3 .The concentration of IgE in the circulation is very low (below 240 ng/ml in healthy individuals); it is the least prevalent antibody type, with a level much lower than the normal level of IgG (5-10 mg/ml) 4 . The half-life of free IgE in the blood is only 2-3 days, while IgE bound to the high-affinity receptor FcεRI on mast cells or basophils is stable for several weeks 5 . Most IgE is bound to cells through its receptors, leaving only a small proportion free in the plasma 6 . Serum IgE levels are very important for the diagnosis of allergies and generally correlate with disease severity 7 . However, the clinical detection of IgE is limited to free serum/plasma IgE, which ignores the large contribution of cell-bound IgE 8 . A number of allergic patients have normal serum IgE levels, which is why the World Allergy Association does not recommend the use of total IgE as a diagnostic guideline for allergy 9 . The level of free IgE in the blood is usually measured by ImmunoCAP 10 .Allergen-specific IgE is the causative agent of allergic disease. Several studies have reported that specific IgE levels correlate well with the severity of allergy; however, a relatively high number of molecules must be defined and produced at a sufficient quality to cover all clinically important allergen specificities 11 . Not all allergens that are in extracts have been defined at the molecular level yet. Other allergens have been well characterized but have not been produced at the quality level required for component-resolved diagnostic tests. The skin prick test is the gold standard for diagnostic allergy tests and is used to confirm allergic sensitization to suspected allergens and provide guidance for the treatment of patients. While...
The etiology of epilepsy remains undefined in two-thirds of patients. Here, we identified a de novo mutation of ATP1A2 (c.2426 T>G, p.Leu809Arg), which encodes the α2 subunit of Na+/K+-ATPase, from a family with idiopathic epilepsy. This mutation caused seizures in the study patients. We generated the point mutation mouse model Atp1a2L809R, which recapitulated the epilepsy observed in the study patients. In Atp1a2L809R/WT mice, convulsions were observed and cognitive and memory function was impaired. This mutation affected the potassium binding function of the protein, disabling its ion transport ability, thereby increasing the frequency of nerve impulses. Our work revealed that ATP1A2L809R mutations cause a predisposition to epilepsy. Moreover, we first provide a point mutation mouse model for epilepsy research and drug screening.
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