Association between skin prick test and serum specific immunoglobulin E to American cockroach allergens in allergic rhinitis patients.

INTRODUCTION AND OBJECTIVES: American cockroach is a common aeroallergen sensitization in allergic rhinitis (AR) patients. Association between skin prick test (SPT) and specific immunoglobulin E (sIgE) to American cockroach allergen remains uncertain. This study aimed to evaluate the association between SPT and sIgE to American cockroach allergen in patients with AR. MATERIALS AND METHODS: This cross-sectional study was conducted in Thai AR patients aged 6-25 years from September 2013 to October 2014. SPT and sIgE to American cockroach allergen were performed and the correlation was calculated using SPSS Statistics version 18. RESULTS: Sixty-seven AR patients, with median age of 15 years were included in this study. SPT and sIgE to American cockroach allergen showed a positive result in 68.7% and 58.2% cases, respectively. Positive SPT or positive sIgE to American cockroach was found in 79.1%. Thirty-two patients (47.8%) tested positive for both SPT and sIgE to American cockroach allergen. Fourteen from a total of 67 cases (20.9%) with negative sIgE had positive SPT to American cockroach, while seven cases (10.4%) with negative SPT had positive sIgE to American cockroach. Moderate correlation was observed between mean wheal diameter (MWD) and sIgE level to American cockroach (r=0.465, p=0.001). No significant correlation was found between MWD of SPT or sIgE level to American cockroach and AR severity. CONCLUSION: A moderate correlation was observed between MWD of SPT and sIgE level to American cockroach. If SPT is negative in allergic rhinitis patients highly suspected of having American cockroach allergy, serum sIgE should be considered and vice versa.

An infant with cartilage-hair hypoplasia due to a novel homozygous mutation in the promoter region of the RMRP gene associated with chondrodysplasia and severe immunodeficiency.

Cartilage-hair hypoplasia (CHH) is a rare autosomal-recessive disorder characterized by short-limbed dwarfism, sparse hair, and immune deficiency. It is caused by mutations in the RMRP gene, which encodes the RNA component of the mitochondrial RNA-processing ribonuclease (RNase MRP). Several mutations have been identified in its promoter region or transcribed sequence. However, homozygous mutations in the promoter region have been only reported in a patient with primary immunodeficiency without other features of CHH. We report on a Thai girl who first presented with chronic diarrhea, recurrent pneumonia, and severe failure to thrive, without apparently disproportionate dwarfism. The diagnosis of CHH was made after the severe wasting was corrected, and disproportionate growth became noticeable. The patient had the typical features of CHH, including sparse hair and metaphyseal abnormalities. The immunologic profiles were consistent with combined immune deficiency. Mutation analysis identified a novel homozygous mutation, g.-19_-25 dupACTACTC, in the promoter region of the RMRP gene. Identification of the mutation enabled us to provide a prenatal diagnosis in the subsequent pregnancy. This patient is the first CHH case with the characteristic features due to the homozygous mutation in the promoter region of the RMRP gene. The finding of severe immunodeficiency supports that promoter mutations markedly disrupt mRNA cleavage function, which causes cell-cycle impairment.

Structural and IgE binding analyses of recombinant Der p 2 expressed from the hosts Escherichia coli and Pichia pastoris.

BACKGROUND: The house dust mite allergen Der p 2 is one of the most important indoor allergens associated with allergic disease. Recombinant Der (rDer) p 2 with high IgE binding activity can be readily produced in Escherichia coli and Pichia pastoris, but the structure and IgE binding of the different methods of preparation have not been compared. METHODS: Secondary structure was assessed by circular dichroism (CD). Intrinsic fluorescence and hydrophobic probe (1-anilinonaphthalene 8-sulphonic acid, ANS) were used to study the Der p 2 hydrophobic cavity. IgE binding was assessed by ELISA inhibition. RESULTS: CD analysis showed the expected secondary structure for both nDer p 2 and refolded Der p 2 prepared from E. coli inclusion bodies but primarily random structure for Der p 2 secreted from P. pastoris. The secreted product, however, had disulphide bonding and could be refolded to a similar structure to natural Der (nDer) p 2 after precipitation with trichloro-acetic or ammonium sulphate. ANS binding and intrinsic Trp92 fluorescence showed that all recombinant proteins were different to nDer p 2 and that the allergen secreted from P. pastoris did not form a hydrophobic cavity. Despite the marked structural changes, all preparations of Der p 2 had similar IgE binding to nDer p 2. CONCLUSION: Despite almost identical IgE binding, rDer p 2 prepared from both E. coli and P. pastoris showed structural differences to nDer p 2. Der p 2 secreted from P. pastoris lacked most of the natural structure, but refolding could induce the natural structure.

Clinical characteristics and outcomes of primary immunodeficiencies in Thai children: an 18-year experience from a tertiary care center.

INTRODUCTION: Early diagnosis and treatment are keys to improve survival of patients with primary immunodeficiency diseases (PID). The clinical characteristics of these patients in Thailand were not well defined. OBJECTIVE: This study aimed to determine the clinical characteristics and outcomes of patients with PID in Thailand. METHODS: Medical records of PID patients in the past 18 years were reviewed. RESULTS: Sixty-seven children were registered. Antibody deficiencies were the most common PID (52.2%), followed by combined T cell and B cell immunodeficiencies (25.4%), other well-defined immunodeficiency syndromes (11.9%), and phagocytic defects (10.4%). The most common presentations of antibody deficiencies, combined T cell and B cell immunodeficiencies, and phagocytic defects were infection in the upper respiratory tract (74.3%), gastrointestinal tract (82.4%), and skin (85.7%), respectively. The highest mortality rate (52.9%) was found in severe combined immunodeficiency. CONCLUSION: These results provide clinical features of PID in Thailand. Knowing these features will lead to prompt diagnosis and appropriate management.

Specific allergy to Penaeus monodon (seawater shrimp) or Macrobrachium rosenbergii (freshwater shrimp) in shrimp-allergic children.

BACKGROUND: Allergy to specific shrimp species has not been studied systematically by oral challenges. A comparison of allergy to different shrimp species, especially seawater or freshwater varieties treatment, would be useful in testing shrimp-allergic subjects. OBJECTIVE: The aim of the study was to identify cases of specific allergy to seawater shrimp, Penaeus monodon (Pm), or freshwater shrimp, Macrobrachium rosenbergii (Mr), among shrimp-allergic children. Comparisons of skin tests using commercial and crude shrimp extracts plus the prick-to-prick (PTP) method were investigated. METHODS: Sixty-eight children with a history of shrimp allergy and skin tests positive to shrimp were orally challenged to both shrimp species. Reactivity to skin prick tests using extracts of Pm (PmSPT), Mr (MrSPT), commercial shrimp (ComSPT), and PTP tests (PmPTP, MrPTP) was compared. RESULTS: Food challenges identified specific allergy to Pm and Mr in 17.65% and 23.53% of the subjects, respectively. Positive and negative challenges to both shrimp species were found in 47.06% and 11.76% of the subjects, respectively. Correlations between the mean weal diameter (MWD) from ComSPT-PmSPT, ComSPT-PmPTP, ComSPT-MrPTP, PmSPT-PmPTP and MrSPT-MrPTP, but not ComSPT-MrSPT, were observed. The MWD from PmSPT and PmPTP were significantly larger in patients with positive than negative challenges to P. monodon (P<0.05). There was a trend that MWD from MrSPT were larger in patients with positive than negative challenges to M. rosenbergii (P=0.058). In the Pm allergy group, PmSPT with an MWD of 30 mm provided 80% predictive probability for positive challenges. PmPTP and ComSPT with an MWD of 22.5 and 20 mm provided 95% predictive probability, respectively. In the Mr allergy group, MrSPT with an MWD of 30 mm provided 95% predictive probability. CONCLUSION: Specific allergy to Pm or Mr was confirmed by food challenges. SPT using crude extracts and the PTP test are useful tools for screening shrimp sensitization before a food challenge. The predictive probability of SPT is helpful where a food challenge is not feasible.

Genetic polymorphisms of major house dust mite allergens.

BACKGROUND: Polymorphic sequence substitutions in the major mite allergens can markedly affect immunoglobulin E binding and T cell responses, but there are few studies on environmental isolates from Dermatophagoides pteronyssinus and none for D. farinae. OBJECTIVE: To determine the sequence variation of the group 1 and 2 allergens from environmental D. pteronyssinus and D. farinae. METHODS: RNA from each species was isolated from homes in Bangkok and the sequence of Der p 1, Der p 2, Der f 1, and Der f 2 determined from cDNA produced by high fidelity polymerase chain reactions. RESULTS: The enlarged data set revealed preferred amino acid substitutions in residues 19, 81, and 215 of Der p 1 as well as sporadic changes. Der p 2 showed frequent variations with clusters of amino acid substitutions, but the canonical Der p 2.0101 was not found in any of 17 sequences. Der f 2 showed variants with clusters of substitutions similar to Der p 2 but in different amino acid positions and without any structural concordance. Der f 1 in contrast to the other allergens had few amino acid sequence substitutions. CONCLUSIONS: The sequence information on variants provides data important for the optimal design of allergen formulations and useful for the genetic engineering and structure-function analyses of the major allergens.

IgE antibodies to omega-5 gliadin in children with wheat-induced anaphylaxis.

BACKGROUND: Wheat can cause severe immunoglobulin E (IgE)-mediated systemic reactions including anaphylaxis but knowledge on relevant wheat allergens at the molecular level is scanty. METHODS: Seven children (aged from 6 months to 13 years) experiencing from 2 to 10 anaphylactic reactions in a year after eating food-containing wheat were examined. Purified omega-5 gliadin was used as an allergen in IgE enzyme-linked immunosorbent assay (ELISA) and in skin prick testing (SPT). Wheat CAP radioallergosorbent test (RAST) and SPT were also examined. RESULTS: All seven anaphylactic children, but none of 15 control subjects had IgE antibodies to omega-5 gliadin in ELISA. Five of the six tested anaphylactic children showed positive SPT to omega-5 and crude gliadin, and all seven had positive wheat CAP RAST and SPT. One child was challenged with wheat, which caused anaphylaxis. After adherence to a wheat-free diet four children remained symptomless and three experienced one to two anaphylactic reactions. CONCLUSION: The present results show that wheat omega-5 gliadin is a major sensitizing allergen in children with wheat-induced anaphylaxis. They also suggest that omega-5 gliadin IgE ELISA could be used as a diagnostic test for this severe allergy.

Additive immunosuppressive effects of 1,25-dihydroxyvitamin D3 and corticosteroids on TH1, but not TH2, responses.

BACKGROUND: The biologic role of the vitamin D analogue 1, 25-dihydroxyvitamin D(3), such as antiinflammatory functions, reduction of cytokine production by T cells, and immunoglobulin production by B cells, has been reported. Such immunomodulatory effects may be potentially useful in dealing with autoimmunity and transplantation. However, whether this hormone has an additive immunosuppressive effect when it is used with corticosteroids has not been investigated, although these agents are commonly used together. OBJECTIVE: Our purpose was to investigate the additive immunomodulatory effects of 1,25-dihydroxyvitamin D(3) on lymphocyte proliferation and cytokine production when used with corticosteroids. METHODS: To investigate the additive effects of 1, 25-dihydroxyvitamin D(3) and dexamethasone on suppression of lymphocyte proliferation, normal PBMCs were cultured in anti-CD3 with or without different concentrations of dexamethasone (0-10(-7) mol/L) plus or minus different concentrations of 1, 25-dihydroxyvitamin D(3) (0-10(-6) mol/L). After 3 days, lymphocyte proliferation was assessed by [(3)H]-thymidine incorporation. To investigate the additive effects of 1,25-dihydroxyvitamin D(3) and dexamethasone on cytokine production, PBMCs were cultured for 3 days in the presence of anti-CD3 with or without 10(-6) mol/L dexamethasone plus or minus 10(-6) mol/L 1,25-dihydroxyvitamin D(3). IFN-gamma, IL-5, and IL-13 production in supernatants were measured by ELISA. RESULTS: Our study demonstrated that, at concentrations of 10(-8), 10(-7), and 10(-6) mol/L, 1,25-dihydroxyvitamin D(3) significantly decreased lymphocyte proliferation compared with an ethanol control (P <.05). The IC(50) for dexamethasone was 4 x 10(-9) mol/L in culture without 1,25-dihydroxyvitamin D(3.) When 10(-9) mol/L of 1,25-dihydroxyvitamin D(3) was added to cultures with dexamethasone, IC(50) became 2 x 10(-9) mol/L. Moreover, when 10(-6), 10(-7), and 10(-8) mol/L of 1,25-dihydroxyvitamin D(3) were added in culture with dexamethasone, IC(50) became less than 1 x 10(-9) mol/L. IFN-gamma production in culture with either dexamethasone or 1,25-dihydroxyvitamin D(3) was significantly decreased compared with media or ethanol control (P <.0001). Moreover, when both agents were added in the same culture, IFN-gamma production was further decreased compared with either agent alone (P <.05). In contrast, 1,25-dihydroxyvitamin D(3) significantly (P <. 0001) increased IL-5 and IL-13, whereas dexamethasone significantly decreased these 2 cytokines (P <.0005). When 1,25-dihydroxyvitamin D(3) was combined with dexamethasone, IL-5 and IL-13 production was increased compared with dexamethasone alone (P <.001). CONCLUSIONS: Our results demonstrate that 1,25-dihydroxyvitamin D(3) has significant additive effects on dexamethasone-mediated inhibition of lymphocyte proliferation. This hormone also has additive effects on inhibition of T(H)1 cytokine production when combined with dexamethasone. However, this hormone upregulates T(H)2 cytokines and inhibits steroid-mediated suppression of cytokines. These findings demonstrate the potential use of 1,25-dihydroxyvitamin D(3) as an immunosuppressive agent when combined with corticosteroids in T(H)1, but not T(H)2, immune responses.

The modulation of cytokine and IgE production by tumor necrosis factor-beta in atopic dermatitis.

Atopic dermatitis (AD) is associated with increased IL-4, IL-5, and IL-13 but decreased IFN-gamma production. This cytokine profile may account for the atopic features of this illness, including IgE upregulation. Recent studies have demonstrated that tumor necrosis factor (TNF)-beta is produced by Th1-like cells, but the cytokine modulation by TNF-beta and the clinical significance of this cytokine in AD is not known. Therefore, this study was carried out to determine the potential role of TNF-beta in AD. In this study, we cultured peripheral blood mononuclear cells from patients with AD and normal subjects with anti-CD3 monoclonal antibodies and investigated the production of TNF-beta by ELISA. The mean +/- SEM of TNF-beta production in AD was significantly lower than normal subjects (p = 0.03). The effect of TNF-beta on cytokine production was investigated by culturing peripheral blood mononuclear cells with anti-CD3 monoclonal antibodies in the presence or absence of TNF-beta. Compared with medium control, TNF-beta significantly decreased IL-5 (p = 0.0004) and IL-13 (p = 0.008) but increased IFN-gamma (p = 0.001) production. The effect of TNF-beta on IgE production was determined by culturing peripheral blood mononuclear cells in the IL-4- and anti-CD40-induced IgE production system. Interestingly, TNF-beta significantly decreased IgE (p = 0.02), but not IgG production compared with medium control. Our study demonstrates that TNF-beta production is downregulated in AD. This cytokine increases IFN-gamma production but decreases IL-5, IL-13, as well as IgE production. These findings suggest a potential role for TNF-beta in the pathogenesis of AD.

Partial mattress encasing significantly reduces house dust mite antigen on bed sheet surface: a controlled trial.

BACKGROUND: The most effective measure in house dust mite antigen reduction is mattress encasing with an impermeable membrane. A reduction in encasing costs will help increase patients' compliance in mite antigen avoidance. OBJECTIVE: To investigate the effectiveness of partial mattress encasing with a nylon sheet produced in Thailand on the reduction of group I mite antigens from beddings. METHODS: Sixty regularly-used beds from the house officers' dormitory of the Siriraj Hospital Mahidol University, Thailand, were randomly matched into two groups according to mite antigen levels. The control group (CG) used only regular cotton bed sheets whereas the partial encasing group (PG) used mattresses partially covered with a locally produced nylon sheet underneath the regular cotton bed sheets. Dust collection from the beddings was performed at baseline, 2, 4 and 6 months after application of the nylon sheet. Mite antigen levels were detected by a two step monoclonal antibody ELISA. RESULTS: Mite antigen levels in both groups were not different at the beginning of the study. The PG had significantly lower group I antigen levels on regular bed sheet surfaces than the CG (P < .004) at the 2, 4 and 6 month timepoints. However, antigen levels on the mattress surface of the PG was significantly higher than the CG at the end of the study (P < .004). The barrier efficacy of the nylon sheet in preventing migration of group I mite antigens from the mattress to the surface of the regular cotton bed sheet was 94% whereas that of the regular cotton bed sheet was 66% (P = .007). CONCLUSION: Partial mattress encasing with a locally made nylon sheet can reduce mite antigens on the regular cotton bed sheet surfaces for up to 6 months.

The modulation of B7.2 and B7.1 on B cells by immunosuppressive agents.

Several recent studies demonstrate that B7.2, but not B7.1, play an important role in allergic inflammation and IgE production. Agents that down-regulate B7.2 may therefore be of benefit for the treatment of Th2-driven allergic diseases. Our current study was carried out to investigate the effect of immunosuppressive agents, cyclosporin A (CsA) and dexamethasone, on B7.2 and B7.1 expression on B cells stimulated with the superantigen, toxic shock syndrome toxin-1 (TSST-1). The analysis of B7.2 and B7.1 on the same cells by flow cytometry demonstrated that TSST-1 up-regulated B7.2+B7.1- but not B7.1+B7.2- on B cells in a dose-dependent fashion. CsA and dexamethasone significantly down-regulated B7.2+B7.1- but up-regulated B7.2-B7.1+ B cells in the presence or absence of TSST-1 (100 ng/ml). Interestingly, the combination of CsA and dexamethasone was much more potent in the inhibition of B7.2 expression than either of these agents alone. As CD40 is known to up-regulate B7.2 expression on B cells, the mechanism of B7.2 down-regulation by CsA and dexamethasone was further studied by investigating the effect of these agents on CD40 expression on B cells. TSST-1 significantly increased CD40 expression on B cells. However, the addition of CsA or dexamethasone significantly down-regulated CD40 expression. Anti-CD40 MoAb significantly reversed the effects of CsA or dexamethasone on B7.2 and B7.1 expression, suggesting that T cell engagement of CD40 plays a role in the mechanisms by which CsA and dexamethasone acts on B cells. These data demonstrate the modulatory effect of CsA and dexamethasone on B7.2 and B7.1 expression on B cells and the potential role of CD40 in mediating this effect.

Prevalence of asthma, rhinitis and eczema in children from the Bangkok area using the ISAAC (International Study for Asthma and Allergy in Children) questionnaires.

Within the past three decades, there has been a rising trend for prevalences of asthma and allergic diseases worldwide, particularly from developed and industrializing countries. In Thailand, limited studies on epidemiology of atopic diseases have indicated relatively low prevalences of these conditions among the Thais. Recently, a standardized phase I questionnaire of the International Study of Asthma and Allergies in Childhood (ISAAC) has been developed to study and to compare geographical and temporal trend for prevalences of asthma, allergic rhinitis and eczema in children. The objectives of phase I ISAAC study in Thailand are to study prevalence of the three most common allergic diseases i.e. asthma, allergic rhinitis and eczema among Thai children of the two age groups (i.e., 6-7 and 13-14 years) living in the Bangkok metropolitan area and to collect basic epidemiologic data of these diseases among these children. The Thai translated version of phase I ISAAC questionnaires was administered to Thai children of the two age groups as above. Questionnaires were answered by parents of younger children, whereas, they were self-administered by 13-14 years old children. In addition, the validated international video questionnaires were used with older children. Fourteen primary schools and 13 secondary schools were randomly selected to cover the entire Bangkok metropolitan area. A total of 7341 questionnaires were eligible for the analysis (3628 from the younger age group and 3713 from the older age group). Data were entered and analysed by the Epi-Info program. The cumulative and 12 month period prevalences of the three conditions for all children were as follows; wheezing, 18.3 per cent, 12.7 per cent; rhinitis, 44.2 per cent, 38.7 per cent; and eczema, 15.4 per cent, 14.0 per cent, respectively. The period prevalence of wheezing for older children (13.6%) was higher than for younger children (11.7%). Prevalences of severe wheeze and exercise wheeze were more common among older children (4.0% and 15.7%). Both age groups reported high percentages for night cough (23.6% and 28.6%). A significantly large number of children from both groups reported symptoms of rhinitis with the majority indicating that symptoms were severe enough to limit their daily activities. Nevertheless, when confined only to those with eye symptoms, the prevalence decreased to 13.1 per cent. Eczema, in contrast to the other two conditions, occurred more frequently among younger children than among older children (period prevalence of 16% vs 9.1%). The rash was of a relatively mild nature since 77 per cent of children reporting symptoms indicated that the rash had cleared within the past 12 months. Allergic conditions are very common among children residing in Bangkok. Compared to the last survey in 1990, the period prevalence of wheezing has increased 4 fold, allergic rhinitis has increased nearly 3 fold whereas, eczema has remained stable. A large number of children in Bangkok are suffering from rhinitis symptoms. Results of this phase I ISAAC study indicate that allergic diseases are perhaps the most common childhood diseases in Thailand and could lead to a substantial economical loss for the country. There is an urgent need for an in-depth study to define epidemiological factors responsible for this increase.

Enhanced expression of B7.2 (CD86) in patients with atopic dermatitis: a potential role in the modulation of IgE synthesis.

Recent studies have suggested that the accessory molecules B7.1 (CD80) and B7.2 (CD86) differ in their capacity to generate Th1 vs Th2 responses. Atopic dermatitis (AD) is a chronic allergic skin disease associated with increased IgE synthesis. To determine the potential role of B7.2 molecules in AD, the present study was conducted to compare the expression of B7.1 vs B7.2 on B cells from patients with AD vs normal subjects or patients with psoriasis. The expression of B7.2 on B cells of AD patients (53.67 +/- 3.10%) was significantly higher than normals (38.02 +/- 4.95%; p = 0.02) and psoriasis patients (40.19 +/- 2.70%; p = 0.006). In contrast, there was no significant difference in B7.1 expression among the three subject groups. Interestingly, total serum IgE from AD patients and normal subjects correlated significantly with B7.2 expression on B cells (r = 0.68; p = 0.004), suggesting a role for B7.2+ B cells in IgE synthesis. Indeed, purified B7.2+ B cells produced significantly more IgE than B7.2- B cells in vitro (p = 0.04). Anti-human B7.2, but not B7.1, mAb significantly (p < 0.05) decreased IgE production by PBMC stimulated with IL-4 and anti-CD40 mAb. Furthermore, B7.2+ B cells had a significantly higher level of IL-4R and CD23 expression than B7.1+ B cells. These data demonstrate the predominant expression of B7.2 in AD, but not psoriasis, and a novel role for this molecule in IgE synthesis.

Nasal cytology in the diagnosis of allergic rhinitis in children.

BACKGROUND: Inflammatory cellular infiltrates of eosinophils and basophilic metachromatic cells are the hallmark of the atopic nasal responses in allergic rhinitis. Nasal cytologic examination for these cells not only establishes the diagnosis of allergic rhinitis but is also useful in the followup of patients with this condition. OBJECTIVES: To determine the usefulness of quantitative nasal cytology as an adjunctive diagnostic tool for children with allergic rhinitis in addition to history, physical examination and allergy skin testing. MATERIALS AND METHODS: Forty-eight children with allergic rhinitis less than 15 years of age were recruited and evaluated for the following variables: symptoms and signs of allergic rhinitis, skin prick tests to common aeroallergens, paranasal sinus radiographs, and nasal cytology. Forty-one normal and healthy children less than 15 years of age served as controls. Nasal mucosal specimens were obtained by scraping the middle one-third of inferior turbinates with Rhinoprobes and were stained with Wright-Giemsa stain. Nasal cytology was examined under a light microscope and graded according to a previously suggested scoring system. RESULTS: There were distinctive differences in the scores for nasal eosinophils and basophilic metachromatic cells between the allergic rhinitis and the control groups (P < .001). The sensitivity for nasal eosinophil scores or nasal basophilic metachromatic cell scores more than 0.5 in the diagnosis of allergic rhinitis was 91.7% with a specificity of 100%, positive predictive value of 100% and a negative predictive value of 91.1%. Presence of polymorphonuclear cells did not correlate with the presence of sinusitis as diagnosed by paranasal sinus radiographs. Nasal eosinophil scores correlated significantly with sign scores (P = .009). House dust mites were the most common allergens sensitized by this group of children (67.4% to 88.4%). CONCLUSION: Nasal cytology is a quick, simple, and inexpensive tool not only for the diagnosis of allergic rhinitis but also for serial evaluations of children with this condition as well.

Upregulation of B7.2, but not B7.1, on B cells from patients with allergic asthma.

BACKGROUND: Allergic asthma is associated with TH2-like cell responses and increased IgE production. Recent studies in mice have suggested that the costimulatory molecule B7.2 (CD86) may influence the development of TH2 cells. OBJECTIVE: We sought to determine the potential role of B7.2 in patients with asthma. METHODS: We performed an analysis of B cells from patients with allergic asthma and healthy control subjects for expression of B7.1 and B7.2 on B cells using five-parameter flow cytometry. RESULTS: We report that atopic patients with asthma who are exposed to allergens have significantly (p < 0.005) higher levels of B7.2 expression on B cells than atopic asthmatic subjects not exposed to allergen in vivo or nonatopic control subjects. In contrast, there were no differences in B7.1 (CD80) expression among the three study subject groups. When peripheral blood mononuclear cells from asthmatic patients or normal control subjects were stimulated with IL-4 or IL-13, the expression of B7.2, but not B7.1, was significantly increased (p < 0.005) on B cells. Interferon-gamma or IL-12 did not affect the expression of either molecule. The functional significance of B7.2 induction by IL-4 in allergic disease was suggested by the increased expression of this molecule on CD23+, but not CD23-, B cells. CONCLUSION: These results indicate that the same B cell involved in allergen presentation also expresses the costimulatory molecule B7.2 and support the hypothesis that this molecule is an important costimulatory molecule in allergic responses, the expression of which can be modulated by TH2-like cytokines.

Clinical applications of cytokines: new directions in the therapy of atopic diseases.

OBJECTIVES: This review will enable the readers to understand the pathogenesis of allergic inflammation, and the role of various cells and cytokines in allergic diseases. Pathogenic cytokines may become key therapeutic targets in the future treatment of allergic diseases. DATA SOURCES: MEDLINE literature search limited to the English language was performed using the relation between specific cytokines and allergic inflammation as well as therapy of allergic diseases. Relevant articles referenced in retrieved sources and current texts on ctyokines and allergic responses were also utilized. RESULTS: The mechanism underlying allergic inflammation involves complex interactions between various cells and cytokines. The immediate reaction is caused mainly by mast cells and followed by a cell mediated response that involves eosinophils, mononuclear cells, neutrophils, T lymphocytes and macrophages. The majority of T cells in early allergic reactions are T helper type 2 (TH2)-like producing IL-4, IL-5, IL-13 but not IFN-gamma. These cytokines regulate IgE synthesis, promote eosinophil differentiation and survival, and induce vascular endothelial adhesion molecules, thus contributing to allergic inflammation. CONCLUSIONS: Although studies of cytokine modulation have utilized animal models of allergic diseases, the increasing availability of recombinant cytokines and cytokine antagonists is likely to lead to more wide scale applications in allergic diseases.