Increased IgE serum levels are unrelated to allergic and parasitic diseases in patients with juvenile systemic lupus erythematosus

OBJECTIVE: The aim of this study was to assess the IgE serum levels in juvenile systemic lupus erythematosus patients and to evaluate possible associations with clinical and laboratory features, disease activity and tissue damage. METHODS: The IgE serum concentrations in 69 consecutive juvenile systemic lupus erythematosus patients were determined by nephelometry. IgG, IgM and IgA concentrations were measured by immunoturbidimetry. All patients were negative for intestinal parasites. Statistical analysis methods included the Mann-Whitney, chi-square and Fisher's exact tests, as well as the Spearman rank correlation coefficient. RESULTS: Increased IgE concentrations above 100 IU/mL were observed in 31/69 (45%) juvenile systemic lupus erythematosus patients. The mean IgE concentration was 442.0 ± 163.4 IU/ml (range 3.5-9936.0 IU/ml). Fifteen of the 69 patients had atopic disease, nine patients had severe sepsis and 56 patients presented with nephritis. The mean IgE level in 54 juvenile systemic lupus erythematosus patients without atopic manifestations was 271.6 ± 699.5 IU/ml, and only nine of the 31 (29%) patients with high IgE levels had atopic disease. The IgE levels did not statistically differ with respect to the presence of atopic disease, severe sepsis, nephritis, disease activity, or tissue damage. Interestingly, IgE concentrations were inversely correlated with C4 levels (r = -0.25, p = 0.03) and with the SLICC/ACR-DI score (r = -0.34, p = 0.005). The IgE concentration was also found to be directly correlated with IgA levels (r = 0.52, p = 0.03). CONCLUSIONS: The present study demonstrated for the first time that juvenile systemic lupus erythematosus patients have increased IgE serum levels. This increase in IgE levels was not related to allergic or parasitic diseases. Our results are in line with the hypothesis that high IgE levels can be considered a marker of immune dysregulation.

Evaluation of anti-allergic activity of gossypin and suramin in mast cell-mediated allergy model.

The mast cell-mediated allergic reactions are involved in many allergic diseases, such as asthma, allergic rhinitis and sinusitis. Stimulation of mast cells initiates the process of degranulation, resulting in the release of mediators such as histamine and an array of inflammatory cytokines. In this report, we investigated the effect of gossypin (a biflavonoid) and suramin (a synthetic polysulphonated naphtylurea) on the mast cell-mediated allergy model, and studied the possible mechanism of their action. Both gossypin and suramin inhibited (P<0.001) compound 48/80-induced systemic anaphylaxis reactions, antiprurities (P<0.001) and reduced the histamine release in rats. Further, both showed significant (P<0.001) protection against rat peritoneal mast cells activated by compound 48/80. Thus, our findings provide evidence that gossypin and suramin inhibit mast cell-derived allergic reactions.

The recurrence of leprosy reactional episodes could be associated with oral chronic infections and expression of serum IL-1, TNF-á, IL-6, IFN-ã and IL-10

The aim of this study was to determine whether the presence of leprosy reactional episodes could be associated with chronic oral infection. Thirty-eight leprosy patients were selected and divided into 2 groups: group I - 19 leprosy patients with oral infections, and group II - 19 leprosy patients without oral infections. Ten patients without leprosy, but presenting oral infections, were assigned to the control group. Leprosy patients were classified according to Ridley and Jopling classification and reactional episodes of the erythema nodosum type or reversal reaction were identified by clinical and histopathological features associated with serum IL-1, TNF-?, IL-6, IFN-? and IL-10 levels. These analyses were performed immediately before and 7 days after the oral infection elimination. Patients from group I presenting oral infections reported clinical improvement of the symptoms of reactional episodes after dental treatment. Serum IL-1, TNF-?, IL-6, IFN-? and IL-10 levels did not differ significantly before and after dental treatment as determined by the Wilcoxon test (p>0.05). Comparison of the 2 groups showed statistically significant differences in IL-1 and IL-6 at baseline and in IL-1, IL-6 and IL-10 on the occasion of both collections 7 days after therapy. Serum IL-6 and IL-10 levels in group I differed significantly at baseline compared to control (Mann-Whitney test; p<0.05). These results suggest that oral infection could be involved as a maintenance factor in the pathogenesis of leprosy reactional episodes.

O objetivo deste estudo foi determinar se os episódios reacionais da hanseníase podem estar associados a infecções orais crônicas. Trinta e oito pacientes com hanseníase foram selecionados e divididos em dois grupos: grupo I & 19 pacientes com hanseníase apresentando infecções orais, e grupo II & 19 pacientes com hanseníase sem infecções orais. Os pacientes foram classificados, quanto à forma clínica da doença, de acordo com Ridley and Jopling, e os episódios reacionais, tipo eritema nodoso e reação reversa, foram identificados pelas características clínicas, histopatológicas associadas à quantificação no soro de IL-1, TNF-?, IL-6, IFN-? e IL-10. Estas analises foram realizadas imediatamente antes e 7 dias após a resolução dos focos de infecção. Pacientes do grupo I aprentando infecções orais relataram melhora clínica dos sintomas dos episódios reacionais após o tratamento odontológico. Os níveis séricos de IL-1, TNF-?, IL-6, IFN-? e IL-10 não diferiram significantemente antes e após o tratamento odontológico, como determinado pelo teste Wilcoxon (p>0,05). As comparações entre os grupos mostrou diferenças estatisticamente significantes nos níveis de IL-1 e IL-6 na coleta inicial e nos níveis de IL-1, IL-6 e IL-10 nas duas coletas 7 dias após o tratamento (teste Mann-Whitney; p<0,05). Estes resultados sugerem que infecções orais estão envolvidas na patogênese dos episódios reacionais da hanseníase, como fatores mantenedores.

Cord Serum Screening Test and the Newborns Allergic Status.

OBJECTIVE: To evaluate the predictive value of a cord serum screen test and possible subsequent development of allergic disease in infants. DESIGN: Cohort study. SETTING: 100 pregnant women were randomly recruited for the study. METHODS: The maternal serum and the cord serum of their matched newborn were analyzed for total serum immunoglobulin E (IgE), gamma interferon (g IFN), house dust mite- Dermatophagoides pteronyssinus allergen (Der p1) and Blomia tropicalis allergen (Blo t5) using immunoassay methods. All infants were followed up for one year. RESULTS: Infants who had allergic diseases in the one year follow-up (n=45) had significantly (P < 0.001) elevated IgE, Der p1, Blo t5, and significantly low g IFN levels in cord serum as compared to the same parameters of infants who did not develop allergic disease in the one year follow-up (n=43). CONCLUSION: In utero exposure to HDM allergens Der p1 and Blot5 is prevalent. We have successfully established a cord serum screening test for predicting allergic diseases in infancy with 93% specificity and sensitivity.

Algorithmic models to predict allergic disease using multiple neonatal markers.

Childhood blindness and visual impairment are as important and perhaps more devastating and disabling than adult onset blindness, because of the long span of life still remaining to be lived. Refractive errors and more particularly myopia, place a substantial burden on the individual and society. School-age children constitute a particularly vulnerable group where uncorrected refractive errors may have a dramatic impact on learning capability and educational potential. This article provides an overview of school eye screening from the perspective of National Program for Control of Blindness (NPCB), Government of India; and challenges, future directions and thrust area envisaged under the program for amelioration of childhood blindness.

A murine model of allergy caused by American cockroach (CR), Periplaneta americana.

An animal model resembling the human immuno-pathological features of CR allergy is needed for CR allergy research, e.g., measuring allergenicity of novel allergens, testing immunotherapeutic efficacies of drugs and vaccines. In this study we develop a murine model of American CR, P. americana allergy. BALB/c mice, 6 weeks old, were individually intraperitoneally injected with three doses (days 0, 7 and 14) of alum adjuvanted-crude extract of P. americana. On days 21 and 23, they were given crude CR extract in PBS intranasally (10 microl) and aerosolically (10 ml) via an air-pressure nebulizer, respectively. Mice received alum alone and PBS instead of the CR extract served as non-allergenic controls. All mice were bled twenty four hours after the nebulization and sacrificed. Their serum samples, broncho-alveolar lavage fluids (BALF), and lung tissues were collected. BALF of all allergen-treated mice had marked cellular infiltration notably neutrophils, eosinophils and lymphocytes. The average total cell count in BALF of the allergenic mice was 1.9 x 10(5) cells/ml which out-numbered those of the non-allergenic controls (8 x 10(4) cells/ml). The eosinophil infiltration was pronounced in lungs of the allergen-treated mice. Specific serum IgE to the CR extract elevated in serum samples of all allergen treated mice and nil in the sera of the controls. None of the mice showed detectable level of IgG2a to the CR extract. RT-PCR revealed that all allergen-treated mice had marked increase of IL-13, IL-4 and TNF-alpha gene expressions, slight increase of IL-5 gene expression, and absence of detectable IFN-gamma gene expression in comparison to the non-allergenic controls. None of the allergen-treated mice and 50% of the non-allergenic controls had IL-12 gene expression as detected by RT- PCR. One allergen treated-mouse (25%) had subpar level of the IL-18 gene expression compared to the controls. Results of the quantitative real-time PCR conformed to those of the RT-PCR. A murine model of P. americana resembling human allergic manifestations was successfully developed.

A quantitative and relative increase in intestinal bacteroides in allergic infants in rural Japan.

Recent studies have suggested that intestinal microbiota play a substantial role in the development of allergic diseases during infancy. We analyzed fecal microbiota in 18 Japanese infants with or without allergy at 6 months and 2 years of age using a cell culture technique. Allergy determination was based on doctor-diagnosed allergic diseases and skin prick tests. There were no differences between 9 allergic and 9 non-allergic infants at 6 months of age in the frequencies or counts of 13 genera and yeast-like organisms. Bifidobacterium was dominant in all infants irrespective of allergy status. At 2 years of age, 8 infants were non-allergic and 10 infants were allergic. Allergic infants at 2 years of age had higher counts of Bacteroides and higher ratios of Bacteroides to Bifidobacterium than non-allergic infants. Despite the small population size used in this study, the results support a significant role of Bacteroides in the pathogenesis of allergy during infancy.

Sensibilidad de la IgE vs. IgE específica en contra alérgenos de ácaros y hongos para el despistaje de alergias tipo I en una población de trabajadores / Total IgE sensitivity against specific IgE against mites and molds in Workers for the screening of type I allergy

Las alergias mediadas por IgE (tipo 1) son enfermedades crónicas que afectan a más del 20% de la población en algunos países. Se analizaron muestras de un grupo de 55 trabajadores del IUPOLC, Caracas, Venezuela, que manifestaron presentar síntomas relacionados con Alergias tipo I, mediante el uso de un cuestionario especialmente diseñado para tal fin. En ichas muestras se determinó la IgE Total Sérica por ELISA (Dr. Fooke Laboratorien, Alemania) y simultaneamente se ensayó un panel de IgE específica compuesto por ácaros y hongos de conocida prevalencia local por la técnica de Allergy Screen® (r-biopharm, Alemania), en aras de calcular la sensibilidad diagnósticada de la IgE Total sérica como marcador para el diagnóstico de Alergias Tipo I ante el hallazgo de valores significativos de IgE Específica para los alergenos seleccionados. Se escogieron los valores de referencia de IgE Total utilizados en la mayoría de los laboratorios clínicos de Venezuela. El valor de sensibilidad diagnóstica obtenido en el estudio para la IgE Total sérica fue de 66,67%, con una especificada de 100%. Valor Predictivo VPP de 100%. Valor Predicitivo Negativo 61,29%. Se discutió la posibilidad de que este valor de sensibilidad pudiese ser incluso menor con la inclusión de mayor número de alergenos y/o pruebas de piel. En conclusión, la utilización de la IgE Total sérica como herramienta diagnóstica de primera instancia (tamizaje y/o screening) de alergia tipo I, debe estar acompañada de la historia clínica del paciente y la prescripción de otros ensayos como la IgE específica. Los laboratorios clínicos locales deben procurar la utilización de mejores esquemas de interpretación (valores de referencia) de la IgE Total sérica que contribuyan a un mejor diagnóstico de esta patología.

IgE mediated allergies (Type I)are chronic diseases that effect more than 20% the population in some countries. We analyzed 55 blood samples from workers of Universitary Institute of Scientific Police, IUPOLC Caracas, Venezuela, that presented Allergies related symptyoms at the moment ofthe study. We used a specially designed survey to register that information. We tested serum Total IgE by ELISA method and a specific IgE using an immunoblott nitrocellulose paner composed with mites and molds allergens of well know local prevalence, in order to calculate the diagnostic sensitivity of serum Total IgE as a marker for screening Type I Allergies compared with allergen sensitivities detected on the individuals. We selected the most common reference values for serum Total IgE used in Venezuela. The sensitivity obtained for serum Total IgE was 66,67% specificity 100%, Positive Predictive Value 100%, and Negative Predictive Value 61,29%. We discussed the possibility that the sensitivity obtained for Total IgE could be oven lower if more number of allergens and skin tests were included on the study. We conclude that the use of Total IgE as screening diagnostic tool for allergies must be used together with clinical history of the patient and other assays like i.e. Specific IgE. Local Clinical Laboratories should promote of better interpretation schemes (reference values) for Total IgE that actually helps to a better diagnosis of this disease.

Native troponin-T of the American cockroach (CR), Periplaneta americana, binds to IgE in sera of CR allergic Thais.

The American cockroach, Periplaneta americana, is the predominant cockroach (CR) species in Thailand and a major source of indoor allergens second only to the house dust mite. The incidence of CR allergy among allergic Thai patients is increasing but basic information on the allergenic components is scarce. In this study a recombinant troponin-T was produced by using cDNA prepared from RNA of the P. americana as a template and PCR primers designed from the P. americana troponin-T sequence deposited in the GenBank database. The recombinant protein (Mr approximately 50) did not bind to IgE in the sera of 18 skin prick test positive CR allergic patients. Rabbit polyclonal antiserum (PAb) against the recombinant troponin-T was produced and used in preparing an affinity column for the purification of native troponin-T from the crude P. americana extract (Mr approximately 47). IgE-immunoblotting revealed that the native protein bound to IgE in 3 of the 18 (16.7%) patients. Our results imply that native P. americana troponin-T, but not its recombinant counterpart, is a minor allergen among the CR allergic Thais.

Parental history of allergy, maternal serum IgE & cord serum IgE.

BACKGROUND: Allergic reactions are responsible for much illness, irritation and disquiet in the life of the child. Recognition and management of allergy in childhood is of great importance to prevent major allergic syndromes. AIM: To correlate cord serum IgE with parental history of allergy and maternal serum IgE. SETTINGS AND DESIGN: In consultation with the attending gynecologist a survey of 950 pregnant women from different parts of Mumbai, visiting gynecology clinics was carried out. METHOD: 100 pregnant women were randomly recruited for the study. Allergic history of both the parents was collected. Blood samples of mothers and matched cord blood samples were collected. Total serum IgE levels were determined using solid-phase immunoradiometric assay. Total serum IgA from each cord blood sample was checked. OBSERVATION & RESULTS: (1) Positive correlation was observed between cord serum IgE and matched maternal serum IgE, with mothers having history of allergy. (2) There was no relation (P=0.99) between cord serum IgE and matched maternal serum IgE, where mothers had no history of allergy. (3) A significant elevation in cord serum IgE was found only with maternal but not with paternal history of allergy. (4) No elevation was found in cord serum IgE (0.5 IU/mL). (6) All cord serum samples had IgA< 0.06 IU/mL ruling out the possibility of contamination with maternal blood. CONCLUSION: The maternal history of allergic disease is associated with an elevated cord serum IgE among newborns. Cord serum IgE is a simple, non-invasive and convenient test, which can supplement the maternal history to provide more discriminative information about the allergic status of the newborn.

A study on the serum levels of interleukin-1beta in bronchial asthma.

Mononuclear phagocytes can be activated through an immunoglobulin E (IgE)- specific mechanism to release pro-inflammatory cytokine like interleukin-1beta (IL-1beta). The present study was conducted to show the inter-relationship between these two parameters in the serum of asthmatic patients. The study included 30 patients of asthma and 10 as control. Out of these 30 cases, 20 patients had stable and 10 had acute asthma. Of the 20 stable patients, 9 were allergic and 11 were non-allergic to either of the 12 allergens used for skin prick test. Serum IgE and IL-1beta levels were measured by enzyme linked immunosorbent assay (ELISA). Total serum IgE levels increased significantly (p < 0.05) in asthma [200.5 +/- 30.91 IU/ml, mean +/- standard error of mean (SEM)] in comparison with the controls (18.15 +/- 4.35 IU/ml). Serum IL-1beta level was higher in allergic (1.94 +/- 0.63 pg/ml) than in non-allergic patients (0.64 +/- 0.21 pg/ml) but it was not statistically significant (p > 0.05). The study suggests involvement of IgE and IL-1beta in the pathophysiology of allergic asthmatic condition. Further studies are required to delineate the inflammatory pathway in asthma and determine stages at which therapeutic interventions can be done.

High levels of soluble herpes virus entry mediator in sera of patients with allergic and autoimmune diseases

Herpes virus entry mediator (HVEM) is a newly discovered member of the tumor necrosis factor receptor (TNFR) superfamily that has a role in herpes simplex virus entry, in T cell activation and in tumor immunity. We generated mAb against HVEM and detected soluble HVEM (SHVEM) in the sera of patients with various autoimmune diseases. HVEM was constitutively expressed on CD4(+)and CD8(+)T cells, CD19(+)B cells, CD14(+)monocytes, neutrophils and dendritic cells. In three-way MLR, mAb 122 and 139 were agonists and mAb 108 had blocking activity. An ELISA was developed to detect sHVEM in patient sera. sHVEM levels were elevated in sera of patients with allergic asthma, atopic dermatitis and rheumatoid arthritis. The mAbs discussed here may be useful for studies of the role of HVEM in immune responses. Detection of soluble HVEM might have diagnostic and prognostic value in certain immunological disorders.

Major house dust mite allergen, Der p I, activates phospholipase D in human peripheral blood mononuclear cells from allergic patients: involvement of protein kinase C

The major house-dust-mite allergen, Der p I, stimulates the phospholipase D (PLD) in peripheral blood mononuclear cells (PBMC) from allergic patients with maximal responses after 30 min exposure. At 30 min, Der p I stimulated PLD activity by 1.4-fold in mild, 1.6-fold in moderate and 2-fold in severe allergic patients over control values (p < 0.05). When the cells were pretreated for 24 h with phorbol myristate acetate to down-regulate protein kinase C (PKC), PLD stimulation by Der p I was largely abolished. These results indicate that in PBMC from allergic patients, Der p I can stimulate PLD activity, and that PKC activation is involved in this stimulation.

Serum Ige levels in patients with allergic problems and healthy subjects

Total serum IgE levels were estimated in 219 patients with various allergic disorders [119 with bronchial asthma, 68 with allergic rhinitis and 32 with urticaria] and 240 healthy age matched subjects. Serum IgE levels were significantly [P < 0.001] higher in healthy males [mean 181 IU/ml] than females [mean 99 IU/ml]. Higher levels were found in the age group 15 to 24 years and lowest in over 55 years. Males had higher IgE levels than females at any given age. Mean IgE levels were significantly [p < 0.001] higher in all three groups of patients than in healthy subjects. Among all age groups, the difference in mean IgE levels between allergic subjects and controls was significant. Positive skin test reactivity [to pollen and dust allergens] was found in 60% patients with asthma, 51% with allergic rhinitis, 46% with urticaria and in 4.5% healthy subjects. Patients with positive skin test had higher mean IgE levels as compared to those with negative skin test, but the difference was insignificant