Decrease in CD23+ B Lymphocytes and Clinical Outcome in Asthmatic Patients Receiving Specific Rush Immunotherapy

Abstract

Rush immunotherapy (RIT) has been documented as useful in the treatment of patients with allergic bronchial asthma. To investigate the mechanisms of its action, we studied changes in the serum levels of total IgE, allergen-specific IgE and IgG4, and expression of CD23 on peripheral blood B cells in patients receiving RIT. Twenty patients with perennial bronchial asthma were evaluated before the beginning of RIT, as well as 6 weeks and 6 months later. Compared to pre-treatment values, the level of Der-p-specific IgG4 and IgE significantly increased after 6 weeks and 6 months of RIT, while the total serum IgE remained unchanged. Furthermore, after 6 months of RIT, the percentage of CD23+ B cells and its CD23 receptor density significantly decreased. Since the symptom score improved and the need for medication decreased, we evaluated RIT as a useful procedure. After 6 months, 30% of patients did not have an asthma attack, with no medication in the last month, while 10% of them were asthma free for the last 3 months. No significant correlation between the clinical improvement, and in vitro changes was found. Furthermore, the observed in vitro changes were not significantly different in patients who responded with clinical improvement, compared to those with unchanged intensity of asthma. In conclusion, during specific RIT we found a significant increase in Der-p-specific IgE and IgG4 antibodies, as well as a moderate decrease in CD23+ B cells and its CD23 receptor density. These findings suggest a change in the lymphokine profile of patients receiving specific immunotherapy, and that the inhibition of IL-4-induced B cell stimulation may be hypothesized as the most important mechanism.

Hyposensitization to allergic reaction in rDer f 2-sensitized mice by the intranasal administration of a mutant of rDer f 2, C8/119S

“…In the present study, we also observed the down‐regulation of IL‐6 and IFN‐γ production by splenocytes in the C2.0 group, which indicated the suppression of T cell reactivity to the sensitizing antigen, wild‐type rDer f 2. Although we could not determine any changes in IL‐4, we found that the expression of CD23, one of the activation markers on B cells, was down‐regulated in the C2.0 group, as in several clinical studies on immunotherapy [ 54, 55]. CD23 expression on B cells has been reported to be higher in allergic patients compared with healthy people, and can be up‐regulated by stimulation with IgE and IL‐4 in vitro [ 56–58].…”

Soluble CD23 Monomers Inhibit and Oligomers Stimulate IGE Synthesis in Human B Cells

“…Levels of soluble CD23 are greatly elevated in rheumatoid arthritis (1,2), systemic lupus erythematosus, and Sjögren's syndrome (3), and the expression of CD23 is enhanced both as membrane and soluble forms in allergic patients (4,5). Strikingly, levels of CD23 are reduced following immunotherapy (6,7). An anti-CD23 antibody, lumiliximab, dramatically reduced IgE levels in patients with allergic asthma in phase I clinical trials (8) and is currently in clinical trials for the treatment for chronic lymphocytic leukemia (9).…”

Specific immunotherapy prevents increased levels of allergen‐specific IL‐4‐ and IL‐13‐producing cells during pollen season

“…Others have reported on a more complex pattern whereby some patients have an increased and others have a decreased level of serum IL‐4 after SIT (18), or that both Th1 and Th2 cytokines are suppressed (19). Still another reported effect of SIT is reduced levels of the soluble low‐affinity receptor for IgE, CD23, known to be of importance in the regulation of IgE antibody production (15, 20, 21).…”