No abstract

As a complication of atopic dermatitis (AD), the incidence of hypoproteinemia is increasing among infants with severe AD in Japan. It can be a life-threatening condition owing to hypovolemic shock as a result of hypoproteinemia and vascular infarction as a result of thrombocythemia. However, the pathophysiology of this condition remains unclear. The objectives of the present study were two-fold. The first objective was to determine the main route of protein loss, i.e. through the damaged skin or the gastrointestinal tract, or as a result of insufficient food intake. The second objective was to identify whether allergy or infection was the cause of severe skin inflammation. Fifteen patients with AD were enrolled who had serum protein levels of 3.2-5.8 g/dl. Specific immunoglobulin E (IgE) and skin test to allergens, stool eosinophils, alpha1-antitrypsin clearance, skin Staphylococcus aureus colonization and superantigens (SAgs) produced by the organism, serum SAg-specific IgE antibodies, serum interleukin (IL)-5, IL-6, IL-12, and interferon-gamma (IFN-gamma) were evaluated. Prominent serous skin discharge was seen in all of the patients and was found to have almost the same protein concentration as serum. Marked thrombocytosis, with a maximum of 1,060 x 103/ml, was seen. Skin culture revealed S. aureus colonization in all patients. SAg-producing S. aureus were found in 84.6% of the patients. The concentration of serum IL-5 was significantly increased and correlated well with the blood eosinophil count. Hence, the main route of protein loss was believed to be through damaged skin. The cause of severe inflammation was thought to be a combination of allergic inflammation and skin colonization by SAg-producing S. aureus. Serum cytokines showed a T helper 2 (Th2) T-cell-mediated pattern. To prevent hypovolemic shock, vascular occlusion, and growth retardation, it is of vital importance to diagnose hypoproteinemia at an early stage and start appropriate therapy.

Human mast cells are derived from CD34+ hematopoietic cells present in cord blood, bone marrow, and peripheral blood. However, little is known about the properties of the CD34+ cells. We demonstrated here that mast cell progenitors that have distinct phenotypes from other hematopoietic cell types are present in cord blood by culturing single, sorted CD34+ cells in 96-well plates or unsorted cells in methylcellulose. The CD34+ mast cell-committed progenitors often expressed CD38 and often lacked HLA-DR, whereas CD34+ erythroid progenitors often expressed both CD38 and HLA-DR and CD34+ granulocyte-macrophage progenitors often had CD33 and sometimes expressed CD38. We then cultured single cord blood-derived CD34+CD38+ cells under conditions optimal for mast cells and three types of myeloid cells, ie, basophils, eosinophils, and macrophages. Of 1,200 CD34+CD38+ cells, we were able to detect 13 pure mast cell colonies and 52 pure colonies consisting of either one of these three myeloid cell types. We found 17 colonies consisting of two of the three myeloid cell types, whereas only one colony consisted of mast cells and another cell type. These results indicate that human mast cells develop from progenitors that have unique phenotypes and that committed mast cell progenitors develop from multipotent hematopoietic cells through a pathway distinct from myeloid lineages including basophils, which have many similarities to mast cells.

Background: The diagnosis of food allergy (FA) is usually based on oral food challenge tests (OFC). However, OFCs occasionally induce severe adverse reactions. CD203c expression on basophils is emerging as a potential diagnostic index. We evaluated whether CD203c expression on basophils would be a useful marker of OFC-associated symptoms in hen’s egg and cow’s milk allergies in children. Methods: Seventy-one patients who had been diagnosed with FA based on OFCs or a convincing history of FA symptoms in the Department of Pediatrics, Sagamihara National Hospital, were recruited. CD203c expression was assessed after stimulation with antigens (egg white, ovomucoid, milk or casein) using allergenicity kits. The CD203c stimulation index (SI = the allergen-induced CD203c expression level divided by the baseline expression level) and the threshold of CD203c expression (the minimum concentration of antigen to induce CD203c SI ≧2) were analyzed in association with tolerance acquisition. Results: For the CD203c SI, the areas under the receiver-operating characteristic curve were 0.72 for egg white, 0.82 for ovomucoid, 0.84 for milk and 0.67 for casein. The positive predictive value for the threshold of CD203c expression was 94.7% for egg white, 100% for ovomucoid, 85.7% for milk and 75.0% for casein. Conclusions: Assessment of food antigen-induced CD203c expression on basophils is useful to determine if children will outgrow FA as well as in decision making regarding whether or not to perform OFCs.