Expression of CD23 antigen and its ligands in children with intrinsic and extrinsic asthma

The role of the low-affinity IgE receptor CD23 in immune reactions has been further emphasized by recent discoveries of novel surface ligands for CD23: CD21, CD11b, and CD11c. We previously observed the difference between the expression of CD23 and CD21 antigens in children suffering from extrinsic asthma when compared to healthy controls. In the present study, we investigated the expression of CD23 and its ligand CD21 on CD20⁺B cells in 44 asthmatic children (23 allergic and 21 nonallergic) using three-color immunofluorescence analysis. In addition, the expression of two other ligands for CD23, CD11b, and CD11c, on T cells (CD3⁺), a subpopulation of T cells (CD4⁺ and CD8⁺), natural killer cells (CD56⁺), and monocytes (CD14⁺) was tested by two-color immunofluorescence analysis in 12 allergic and 14 nonallergic children. We found that children with extrinsic asthma had higher levels of CD23⁺ B cells than those with intrinsic asthma. No difference was observed in the percentage of either CD23⁺CD21⁺ or CD23^- CD21⁺ B cells. The CD11b antigen was expressed on each tested population, but only on CD4⁺ T cells was CD11b significantly increased in children with extrinsic asthma. CD11c was expressed mainly on monocytes, and no difference was observed between tested groups. The increased percentage of CD11b antigen on CD4⁺ T cells and the increased percentage of CD23 antigen on B cells in children with extrinsic asthma provide further evidence of the immunologic differences between intrinsic and extrinsic asthma.     

Serum levels of sCD23 and sCD25 in children with asthma and in healthy controls*

To investigate whether markers of lymphocyte activation are useful markers of disease activity in childhood asthma, we studied serum levels of soluble CD25 (receptor for IL-2) and soluble CD23 (low-affinity receptor for IgE) in 178 children (aged 2-18 years) suffering from mild to moderate asthma (mean asthma severity score: 2, range: 1–4), and in 175 healthy age-matched controls. Levels of sCD23 and sCD25 were invesely related to age. sCD23 was lower in patients with asthma (means per age group: 4.93–2.29 ug/1; controls: 6.92–4.11 ug/1, P <0.05), while sCD25 tended to be higher (1601–597 kU/ml, controls: 1350–-661 kU/ml, P = NS). sCD25 correlated significantly with asthma severity score (r=0.41; P <0.01) and MEF₂₅ (maximum experatory flow at 25% of vital capacity, r= -O.43; P<0.05) in children <10 years, while sCD23 correlated with asthma severity (r=O.28; P <0.05) in children > 10 years. On follow-up, levels of sCD25 normalized with clinical improvement. In children with nonatopic asthma, levels of sCD25 were significantly higher than in atopic patients. Our observations provide further evidence of the role of T-cell activation in asthma. Monitoring of lymphocyte activation markers, particularly levels of sCD25, may be useful in the follow-up of asthmatic children.     

Expression of sCD23 in atopic and nonatopic blood donors: correlation with age, total serum IgE, and allergic symptoms

Although structure, biologic activities, and expression of the low-affinity IgE receptor (Fc_eRII, CD23) have been investigated, the diagnostic value for allergies of this molecule and its soluble circulating fragment (sCD23) remains unclear. Therefore, serum sCD23 levels were measured in 203 blood donors. They were divided into atopic and nonatopic subjects by allergy history, physical findings of allergic symptoms, and corresponding specific circulating IgE antibodies. The group consisting of nonatopic subjects was divided into four age categories in order to exclude age-dependent variations in the expression of the low-affinity IgE receptor. In our study population, sCD23 serum levels were not influenced by age. Furthermore, no significant differences, especially no decrease in serum sCD23 levels, between the four nonatopic age groups were detected. There was no significant increase of sCD23 serum levels in atopic subjects in comparison with nonatopic blood donors. In addition, no correlation between total IgE levels and sCD23 serum levels could be detected, in either the group of atopic donors or the group of nonatopics. Our data suggest that the circulating low-affinity IgE receptor does not appear to be an additional general marker for the diagnosis of allergies, as previously suggested.     

Peripheral eosinophil counts as a marker of disease activity in intrinsic and extrinsic asthma

Background: Recently it has been suggested that the bronchospasm and hyperresponsiveness phenomena observed in asthma are secondary to the actions of the eosinophils; the purpose of this study was to evaluate the relationship between the peripheral number of eosinophils and various markers of disease activity in a group of asthmatics examined in childhood (mean age 10 years) and early adulthood (mean age 21 years). Methods: The relationship between eosinophil count and pulmonary function (FEV₁), respiratory symptoms, bronchial responsiveness to histamine and diurnal variation in peak expiratory flow rate (PEF) was studied in 70 subjects with bronchial asthma, of whom 24 had intrinsic and 46 extrinsic asthma. Self-reported symptoms of asthma were graded on a scale from 0 to 5, where 0 = no symptoms within the preceding 12 months and 5 = daily including nocturnal symptoms, and histamine responsiveness was analysed by means of the dose-response slope (DRS). Results: In both childhood and adulthood, a direct correlation was found between blood eosinophil count and symptom score (r= 0.69, P< 0.001 and r= 0.58, P < 0.001, respectively), whereas inverse correlations were observed between number of eosinophils and FEV, % predicted (r= .0.75, P < 0.001 and r= 0.80, P < 0.001. respectively). Furthermore, in adulthood, eosinophil count was found to be significantly correlated to hisiamine responsiveness (log DRS) (r= 0.65, P < 0.001) and diurnal PEF variation (r= 0.81, P < 0.001); these correlations were also noted after dividing the subjects into intrinsic and extrinic asthmatics. In both groups of subjects a significant inverse correlation was also found between histamine responsiveness and pre challenge FEV₁% predicted. The eosinophil count in childhood was weakly correlated to the symptom score in adulthood (r= 0.29, P < 0.02). Conlusions: This study showed a relationship between eosinophil count and seventy of asthmatic symptoms, level of pulmonary function, histamine responsiveness and diurnal variation in PEF in both intrinsic and extrinsic asthma; suggesting that the peripheral eosinophil count reflects asthmatic activity, and possibly the degree of inflammation in the airways, in both children and adults. Furthermore, a low number of eosinophils in childhood might be related to a relatively favourable prognosis with regard to symptoms of asthma in early adulthood.     

Correlation of plasma hormone levels and peripheral circulating lymphocyte subpopulations during human pregnancy

Using monoclonal antibodies (OKT3, OKT4, OKT8) peripheral blood lymphocyte subsets were determined in 40 normal primiparous pregnant women and compared with those of 31 nonpregnant controls. In pregnant women plasma concentrations of estradiol, progesterone, human placental lactogen (HPL), beta subunit of human chorionic gonadotropin (beta HCG), and alpha-fetoprotein were measured by means of radioimmunoassay. We studied if correlations between peripheral lymphocyte subsets and plasma hormone levels might exist. We observed in pregnant women from 10 to 40 wk of amenorrhea a decrease in the percentage of OKT3 and OKT8 cells, and during the course of pregnancy an increase in the percentage of OKT4 cells. This increase inversely correlated with plasma beta HCG levels and directly correlated with plasma HPL levels.     

Different serum soluble Fas levels in patients with allergic rhinitis and bronchial asthma

BACKGROUND: The pathogeneses of allergic rhinitis and bronchial asthma are believed to be closely mutually related because of the similar dynamics of allergy-inducing cells and molecules and clinical overlap. In this study, we compared these diseases in the dynamics of cell apoptosis-regulating molecules. METHODS: Allergic rhinitis patients (n=36), bronchial asthma patients (n=22), and healthy subjects (n=32) were subjected to measurement of serum (soluble Fas) (sFas) levels during the stable and attack disease phases by a sandwich enzyme-linked immunosorbent assay. RESULTS: Serum sFas levels in patients with allergic rhinitis during the attack phase were significantly lower (P<0.0001) than those in healthy individuals. There were no differences between them during the attack and stable disease phases. In contrast, serum sFas levels in patients with bronchial asthma during the attack phase were higher (P<0.0005) than those in healthy individuals. Interestingly, the levels during the attack phase were lower (P<0.002) than those during the stable phase. CONCLUSIONS: Our results suggest a different pathogenesis for allergic rhinitis and bronchial asthma at the cell apoptosis-linked step.     

Allergy to cockroaches in patients with asthma and rhinitis in an urban area (Madrid)

Previous studies have established that cockroach allergens are important sensitizing agents in the induction of rhinitis and asthma principally in urban areas. This study was undertaken to assess skin test reactivity and specific IgE antibody reactivity to extracts of Periplaneta americana (Pa.), Blattella germanica (B.g.), B. orientalis (B.o.), and a fecal extract of B. germanica (FEB.g.) in a group of patients with rhinitis and asthma living in an urban area in Europe. We examined clinical characteristics and aeroallergen sensitivities of 171 consecutive Madrid urban patients with rhinitis and asthma who met the criteria for the study. A comprehensive clinical evaluation was followed by skin prick test with common allergens and saline extracts of P.a., B.g., B.o., and FEB.g. and measurement of serum specific IgE antibody to cockroach extracts. The age of patients ranged from 7 to 68 years (mean 20.4 ± 16). A total of 153 (90.5%) subjects were atopic and 19 (10%) were considered nonallergic. Pollen sensitivity (66.5%) was most prevalent, distantly followed by sensitivity to cockroach (25.7%), mite (20%), cat (15.5%), Alternaria alternata (14.5%), dog (14%), and food (2%). Skin test reactivity to cockroach extracts was 37 (21.6%) to B.o., 20 (11.6%) to Pa., 19 (11.1%) to B.g. and five (2.9%) to FEB.g. Twenty-one of these patients had rhinitis, 19 rhinitis and asthma, and one only asthma; 26 had perennial symptoms, while 16 had seasonal (spring) symptoms; three (1.7%) patients had only positive prick test to cockroach; all had perennial rhinitis and/or asthma. Eighteen (10.5%) patients had specific serum IgE (RAST 1 or 2) to B.o., 13 (7.6%) to Pa., and six (3.5%) to B.g. Eighty (46.7%) patients had visual evidence of cockroach infestation in their home, mostly B.o.; 31 had positive prick test to cockroach (P< 0.0003). The results indicate that sensitivity to outdoor allergens (pollen) is more prevalent than to indoor allergens. Cockroach sensitization is the most important indoor allergen in our area, and B.o. accounts for most cockroach sensitization.     

Expression of naive/memory (CD45RA/CD45RO) markers by peripheral blood CD4+ and CD8+ T cells in children with asthma

Introduction: The role of CD4⁺ T cells in the immunopathogenesis of asthma is well documented. Little is known about the role of CD8⁺ T cells. The aim of this study was to assess peripheral blood subsets of CD4⁺ and CD8⁺ T cells expressing naive/memory markers (CD45RA⁺/RO⁺) and the activation marker (CD25⁺) in children with allergic asthma. Materials and Methods: Peripheral blood mononuclear cells were isolated from children with allergic asthma and healthy children. T cell subsets were analyzed by flow cytometry for the expressions of CD45RA, CD45RO, and CD25. In this study, some differences in the memory compartment of peripheral blood T cells between asthmatic children and healthy controls were detected. Results: The absolute number of CD8⁺ T cells expressing CD45RO was significantly elevated and the percentages of CD3⁺ T cells expressing activation marker CD25 and of CD4⁺ T cells expressing memory marker CD45RO were significantly lower in children with asthma compared with controls. No correlation was found between severity of asthma and peripheral blood lymphocyte subsets. Conclusions: There were some differences in the memory compartment of peripheral blood T cells between asthmatic children and healthy controls. The increase in the number of CD8⁺ T cells expressing the memory marker (CD45RO) in children with allergic asthma may indicate that CD8⁺ T cells play a role in the pathogenesis of asthma.     

Systemic levels of ceruloplasmin oxidase activity in allergic asthma and allergic rhinitis

Context: The role of ceruloplasmin oxidase activity (COA) involving the interaction of oxidant and antioxidant balance in allergic diseases is still unknown.

Objective: Our study was designed to examine the changes in COAs in severe persistent asthma-allergic rhinitis, new diagnosed allergic asthma-allergic rhinitis and allergic rhinitis patients.

Methods: The study included 20 age- and sex-matched healthy individuals as control (Group I); Group II included 15 newly diagnosed allergic asthma-allergic rhinitis; Group III included 15 patients with severe persistent asthma-allergic rhinitis and in the fourth group there were 20 patients with allergic rhinitis. Group III was divided in two groups, severe persistent asthma-allergic rhinitis who were pre-(III-A) and post-treated (III-B) with omalizumab. Group IV was divided to two groups, pretreatment (IV-A) and posttreatment (IV-B) with specific subcutaneous immunotherapy modalities. All the posttreatment measurements were 12 months after the therapy. All the patients were assessed by the skin prick test, high sensitive C-reactive protein (hs-CRP) and COA.

Results: There were significant differences between Group I and Groups III-A, III-B, IV-A and IV-B; Group II and Groups III-A, III-B, IV-A and IV-B; Group III-A and Groups III-B, IV-A and IV-B; Group III-A and Groups IV-A and IV-B; and Group IV-A and IV-B. Interestingly, there was a correlation between the hs-CRP and COA levels in Group III-A.

Conclusions: Our data suggest that hs-CRP and COA levels might be an indicator of an inflammation and important in revelation of patients with allergy related diseases, especially of asthma patients.     

An assessment of peripheral immunity in patients with sarcoidosis using measurements of serum vitamin D3, cytokines and soluble CD23

The aetiology of the peripheral anergy in sarcoidosis is unclear. To investigate this further we measured the serum levels of several factors important in different aspects of immune regulation to obtain a profile of those factors which promote and inhibit immune activation in sarcoidosis. Thirty-seven patients with sarcoidosis and 20 healthy controls of similar sex and age comprised the study group. Serum IL-10, interferon-gamma (IFN-γ), soluble CD23 (sCD23), IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1β and tumour necrosis factor-alpha (TNF-α) were measured using in-house ELISAs. Vitamin D3 was measured using a radioreceptor assay. Serum levels of sCD23 and IL-10 were significantly elevated in patients with sarcoidosis relative to controls (median 13.9 versus 9.5 arbitrary units/ml, P < 0.01 for sCD23, and 9.6 versus 5.0 pg/ml, P < 0.04 for IL-10). Regardless of steroid therapy or disease activity, serum levels of IFN-γ, TNF-α, IL-1β, GM-CSF and IL-8 were no different in patients with sarcoidosis and controls. Vitamin D3 levels were significantly higher in patients with sarcoidosis versus normal controls (medians 78.0 versus 56.0, P < 0.001), active sarcoidosis (n = 20) versus inactive disease (n = 17) (medians 81.5 versus 66.0, P < 0.03) and active sarcoidosis versus controls (medians 81.5 versus 56.0, P < 0.0002). The levels were no different between patients with inactive sarcoidosis and controls. We suggest that IL-10 and vitamin D3 may contribute to the peripheral anergy in sarcoidosis. The elevated serum sCD23 suggests an increase in peripheral humoral immunity. Consistent with a quiescent peripheral immune system, factors capable of monocyte/macrophage activation (TNF-α, IFN-γ, GM-CSF and IL-8) were not elevated in the peripheral circulation.     

严重创伤患者外周血sCD14水平变化及临床意义

目的:观察重度创伤患者sCD14水平的变化与病情的关系.方法:ELISA法检测外周血单个核细胞体外培养上清液和外周血血浆中sCD14含量和五分类法检测外周血单核细胞数量和比率.结果:22例重度创伤患者手术24h后外周静脉血单个核细胞培养上清液中的sCD14水平(4.50ng/ml)较健康对照组(1.17ng/ml)明显升高(P＜0.05),而手术后48h的sCD14有明显降低(1.15 ng/ml),血浆中的sCD14在手术前较高(11.85 ng/ml),同时外周血单核细胞数量和比率不同程度升高.结论:在重度创伤患者检测sCD14和外周血单核细胞的变化有一定的临床意义.     

The role of CD23 on allergen-induced IgE levels, pulmonary eosinophilia and bronchial hyperresponsiveness in mice

BACKGROUND: The role of Immunoglobulin (Ig)E in inflammation is the subject of considerable study and a number of studies have shown conflicting evidence for its role in eosinophil recruitment and bronchial hyperresponsiveness in a number of murine models. The low affinity IgE receptor, CD23, is known to act as a negative regulator of IgE production and we have used knockout mice deficient in CD23 to investigate the role of IgE in eosinophil recruitment and bronchial hyperresponsiveness in a murine model of airway inflammation. OBJECTIVE: To study the role of the low affinity FcepsilonII receptor, CD23 in IgE production, lung inflammation and bronchial hyperresponsiveness. METHODS: Wild-type and CD23 knockout C57Bl/6 mice (CD23-/-) were immunized by intraperitoneal injection with ovalbumin on days 0 and 14 and challenged with aerosolized antigen on day 21 for a period of up to 1 week. Blood samples, bronchoalveolar lavage and lung tissue samples were obtained to determine serum IgE levels and inflammatory cell numbers, respectively. Furthermore, airway resistance was measured to increasing concentrations of aerosolized 5-hydroxytryptamine in order to evaluate the effect of CD23 deficiency on bronchial hyperresponsiveness to antigen challenge. RESULTS: Sensitization of wild-type C57Bl/6 mice to ovalbumin resulted in elevated levels of total serum IgE and ovalbumin-specific IgE, which was significantly augmented in CD23 knockout C57Bl/6 mice (CD23-/-). A significant increase in the percentage of eosinophils recovered in bronchoalveolar lavage fluid from wild-type and CD23-/- mice was observed 24 h following 3 or 7 days aerosol exposure with ovalbumin (10 mg/mL). At 3 days, the increase in the percentage of eosinophils was significantly greater in CD23-/- groups. Immunohistochemical analysis of lungs sections revealed the presence of CD3+, CD4+ and CD23+ cells in wild-type mice but a lack of immunofluorescence of CD23+ cells in CD23-/- mice. In wild-type ovalbumin-immunized mice, bronchial hyperresponsiveness to aerosolized 5-hydroxytryptamine was observed following a 3-day antigen challenge, which was significantly greater in CD23-/- ovalbumin-immunized mice. CONCLUSION: These studies demonstrate that CD23-/- mice have increased capacity to produce IgE consistent with the view of a negative feedback role for membrane-bound CD23 and under such conditions, may account for the greater numbers of eosinophils recruited to the airways and bronchial hyperresponsiveness observed following acute but not chronic antigen challenge.     

Current allergic asthma and rhinitis: diagnostic efficiency of three commonly used atopic markers (IgE, skin prick tests, and Phadiatop®)

Total serum IgE, Phadiatop®, and the skin prick test (SPT) are commonly used to diagnose atopic diseases. However, no large study has ever been done to test their diagnostic efficiency. We studied the diagnostic value of these three atopic markers in 8329 well-randomized adults from the Swiss Population Registry. The prevalence of current allergic asthma (CAA) was 1.8% and of current allergic rhinitis (CAR) 16.3%. The prevalences of positive Phadiatop, positive SPT (at least, one out of eight SPT to common aeroallergens with a wheal of >3 mm), and positive total IgE (IgE >100 kU/1) were 29, 23, and 23%, respectively. To diagnose CAA and CAR. the sensitivity of Phadiatop was significantly higher than that of SPT (72.5% vs 65.4%, 77.1% vs 68.4% respectively; P<0.01 and <0.001) and IgE (72.5% VA- 56.9%, 77.1% vs 43.9%, respectively; both p<0.001). The sensitivity of SPT was significantly higher (68.4% vs 43.9% P<0.001) than that of IgE to diagnose CAR. When CAA and CAR were excluded, the SPT specificity was significantly higher than that of Phadiatop (77.8% vs 71.9% and 85.9% vs 80.5%, respectively; both P<0.001): when CAR was excluded, SPT was significantly higher than IgE (85.9 vs 81.4%; P<0.001). SPT had significantly the best positive predictive value for CAA (5.2% for SPT vs 4.6% for both IgE and Phadiatop; both P<0.001) and CAR (48.7% for SPT vs 43.5% for Phadiatop and 31.6% for IgE; both P<0.001). The three markers of atopy had roughly the same negative predictive value (NPV) for CAA, but IgE had a significantly lower NPV for CAR than SPT and Phadiatop (88.1% vs 93.3% and 94.7%, respectively; both P<0.001). The diagnostic efficiency of SPT was significantly higher than that of Phadiatop (83.1% vs 79.9% and 77.6 vs 71.9%, respectively; both F<0.001) to diagnose CAR and CAA. IgE and SPT had equal efficiency (77.6%), which was significantly higher than that of Phadiatop, to diagnose CAA (71.9%; both P<0.001). In conclusion, SPT have the best positive predictive value and the best efficiency to diagnose respiratory atopic diseases. Furthermore, SPT give information on sensitivity to individual allergens and should therefore be used primarily by clinicians to assess respiratory allergic diseases. Moreover, they are cheaper and provide immediate, educational information for both patient and physician.     

The Importance of Specific IgG and IgE Autoantibodies to Retinal S Antigen, Total Serum IgE, and sCD23 Levels in Autoimmune and Infectious Uveitis

Autoimmunity plays an important role in the development of uveitis. The uveitis are linked to Th1 or Th2 lymphocyte activation. We studied 41 patients with uveitis, divided into autoimmune uveitis (n = 32) and infectious uveitis (n = 9), 30 normal controls, and 20 asthmatic atopic without ocular diseases. The infectious uveitis patients were separated into bacterial (n = 6) and toxoplasmic (n = 3) retinochoroiditis. We measured IgE and sCD23 serum levels and specific IgG and IgE to retinal S antigen by ELISA tests. The IgE levels were 500 ± 325 kU/L in autoimmune uveitis, 57 ± 35 kU/L in bacterial uveitis, 280 ± 38 kU/L in toxoplasmic retinochoroiditis, 75 ± 32 kU/L in the controls, and 557 ± 243 kU/L in atopics (P < 0.0005). The sCD23 levels were 10.4 ± 5.4 ng/ml in autoimmune uveitis, 3.7 ± 1.17 ng/ml in bacterial uveitis, 6.76 ± 1.36 ng/ml in toxoplasmic retinochoroiditis, 3.4 ± 1 ng/ml in controls, and 8.35 ± 2.2 ng/ml in atopic patients (P < 0.005). The specific IgG to retinal S antigen was positive in 27 of 32 cases, and the specific IgE to retinal S antigen was positive in 22 of 32 autoimmune uveitis. The bacterial uveitis patients as well as the controls were negative for both autoantibodies to retinal S antigen. The toxoplasmic retinochoroiditis patients presented specific IgG and IgE to retinal S antigen in two of three cases, respectively, one of them with overlap of both antibodies. These results suggest the importance of specific IgG and IgE to retinal S antigen in autoimmune uveitis, which, along with higher IgE and sCD23 levels, reveal Th2 activation.     

Pharmacologic and anti-IgE treatment of allergic rhinitis ARIA update (in collaboration with GA2LEN)

The pharmacologic treatment of allergic rhinitis proposed by ARIA is an evidence-based and step-wise approach based on the classification of the symptoms. The ARIA workshop, held in December 1999, published a report in 2001 and new information has subsequently been published. The initial ARIA document lacked some important information on several issues. This document updates the ARIA sections on the pharmacologic and anti-IgE treatments of allergic rhinitis. Literature published between January 2000 and December 2004 has been included. Only a few studies assessing nasal and non-nasal symptoms are presented as these will be discussed in a separate document.