ABSTRACT: Although the efficacy of allergen-specific sublingual immunotherapy (SLIT) is now accepted, the underlying mechanisms remain elusive. Such mechanisms are better documented in the case of subcutaneous immunotherapy (SCIT). In order to understand the T-lymphocyte response in patients receiving SLIT, we compared children with respiratory disease monosensitized to Dermatophagoides pteronyssinus receiving SLIT or SCIT over a 2-yr period. Peripheral blood was obtained before beginning immunotherapy, and after 3 months, 1 yr and 2 yr. Total IgE, specific IgE and IgG4 to D. pteronyssinus were determined in serum. T-cell markers (CD3, CD4, CD8, CD25) and intracellular cytokine production (TNF-alpha, IL-2, IL-4 and IFN-gamma) were determined in peripheral blood mononuclear cells (PBMC) by flow cytometry. No differences between SCIT and SLIT were detected in the clinical variables or in the subjective evaluation. Although an increase in specific IgE and IgG4 was only detected in SCIT, a significant decrease in the specific IgE/IgG4 ratio was found in both groups. SCIT and SLIT experienced an increase in the CD4/CD8 ratio over time, but an increase in the CD4(+)CD25(+) and a decrease in the CD8(+)CD25(+) subsets were only found with SCIT. A slight shift from a Th2 to a Th1 pattern, measured by the IFN-gamma/IL-4 ratio, was only detected in the CD4 T cells with SCIT. A decrease in both groups was found in TNF-alpha and IL-2 production over time. Children with respiratory allergic diseases receiving SCIT or SLIT had a different immunologic response in peripheral blood during treatment, though the clinical improvement was similar. Whether SLIT induces a mucosal protective response should be studied.
Pediatric Allergy and Immunology 06/2008; 19(3):210-8. · 2.46 Impact Factor
ABSTRACT: Toxic epidermal necrolysis (TEN) is a severe disease often induced by drugs. Treatment is controversial, although intravenous immunoglobulins (IVIGs) have been effective.
To report the case of a child with TEN after lamotrigine treatment, who improved 24 hours after IVIG administration.
Sequential blood and blister fluid samples were obtained for flow cytometry and reverse transcriptase-polymerase chain reaction analyses.
The first blood sample, taken before IVIG administration, showed normal levels of lymphocyte subsets and CLA (4.0%) but high levels of activated lymphocytes (CD69) (18.0%). After treatment, the CLA+, CD69+, and memory cells increased until day 7, decreasing to normal values at days 15 and 30. In the blister fluid samples, taken on day 1, there were high levels of CD8+ (70.2%; CD4/CD8 ratio, 1:5), CLA+ (18.8%), and CD69+ (70%) cells, decreasing 24 hours after IVIG administration. In the blood samples, there was a Th1 cytokine pattern initially, tending to Th0 with time. Perforin, granzyme B, and Fas ligand were only observed before IVIG administration.
A single high dose of IVIG interrupted the progression of skin disease and reduced the expression of the apoptotic markers. The immunologic changes, first seen in blister fluid and remaining several days in peripheral blood, indicate that T cells were first recruited to the skin and then recirculated to blood.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 08/2003; 91(1):86-91. · 2.83 Impact Factor
ABSTRACT: Adverse reactions to tetanus toxoid (TT) vaccine are mostly mild and limited to the injection site. However, immunoglobulin (Ig)E-mediated reactions may occur, and the incidence of anaphylactic responses to TT immunization is 0.001%. When TT induces an allergic reaction, the potential causative agents can be TT antigens, thimerosal or aluminum phosphate.
We studied four children who developed immediate urticaria after TT vaccine, soon after the reaction and 5 years later.
Skin tests were performed separately with TT vaccine and two vaccine components, thimerosal and aluminum phosphate, and the diagnosis was confirmed by provocation test. IgE and IgG antibodies to TT and their specificities were determined. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting were performed to characterize the antigenic proteins.
All four children were immediate skin test-positive to TT, but negative to thimerosal and aluminum phosphate; 3 developed a reaction after intramuscular provocation using increasing doses of TT vaccine; and 1 refused to be tested. All these tests were negative in five controls, all of whom received TT vaccine and developed only local swelling at the site of application 24 hours after vaccine administration. After 5 years the IgG antibodies were still high in all cases and the IgE antibody values fell by 50%. Patients allergic to TT vaccine produced IgE and IgG antibodies, which decreased at different rates but remained for at least 5 years. The pattern of antibody decrease was confirmed by radioallergosorbent test, enzyme-linked immunoadsorbent assay, or immunoblotting assay. IgE and IgG antibodies recognized two proteins derived from TT, of 150 and 50 kDa, corresponding to the intracellular form and to a chain of the extracellular form of the tetanus neurotoxin.
In children with immediate allergic reactions to TT vaccine, antibodies may persist for at least 5 years, requiring evaluation by skin and/or in vitro tests before subsequent treatment.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 03/2003; 90(2):238-43. · 2.83 Impact Factor