Nihal Mete

Early suppression of basophil activation during allergen-specific immunotherapy by histamine receptor 2

BACKGROUND Early desensitization of FcεRI-bearing mast cells and basophils has been demonstrated in allergen-specific immunotherapy and drug desensitization. However, its mechanisms have not been elucidated in detail. Histamine is one of the main mediators released on FcεRI triggering of basophils and mast cells, and it exerts its functions through histamine receptors (HRs). OBJECTIVES We sought to investigate HR expression on basophils of patients undergoing venom immunotherapy (VIT) and its effect on allergen, IgE, and FcεRI cross-linking-mediated basophil function and mediator release. METHODS Basophils were purified from the peripheral blood of patients undergoing VIT and control subjects and were studied functionally by using real-time PCR, flow cytometry and ELISA assays. RESULTS Rapid upregulation of H2R within the first 6 hours of the build-up phase of VIT was observed. H2R strongly suppressed FcεRI-induced activation and mediator release of basophils, including histamine and sulfidoleukotrienes, as well as cytokine production in vitro. CONCLUSION Immunosilencing of FcεRI-activated basophils by means of selective suppression mediated by H2R might be highly relevant for the very early induction of allergen tolerance and the so-called desensitization effect of VIT.

Comparison of Der p1-specific antibody levels in children with allergic airway disease and healthy controls

Although children, with allergic airway disease, who are sensitized to house‐dust mite (HDM) are known to have increased levels of allergen‐specific IgE and IgG, the association between the quantity of those immunoglobulins and the clinical features of disease is not yet well established. The purpose of this study was (i) to evaluate Der p1‐specific IgA, IgG1, IgG4, and IgE levels of children with HDM‐allergic asthma and allergic rhinitis and to compare it with that of healthy controls (ii) to assess the association with disease duration. A total of 73 patients were included. Of those, 58 had asthma (M/F: 27/31, mean age 7.9 ± 2.7 yr) and 15 were diagnosed as allergic rhinitis (M/F: 8/7, mean age 10.1 ± 4.0 yr) without asthma. Twenty‐five (M/F: 13/12, mean age 9.5 ± 4.2 yr) non‐allergic children were included as healthy controls. Data on age at onset and duration of disease were recorded. Then, Der p1‐specific IgA, IgG1, IgG4, IgE levels were measured in all of the 98 subjects by ELISA. Comparison of Der p1‐specific antibody levels of patients and controls revealed that Der p1‐specific IgG1, IgG4 and IgE levels of patients with asthma (p = 0.012, p = 0.021, p = 0.004, respectively) were significantly higher than healthy controls. Also, the ratio of Der p1‐specific IgA/IgE was significantly lower in asthmatic children when compared with children with allergic rhinitis and controls (p = 0.029, p < 0.001, respectively). Der p1‐specific IgG1, IgG4, IgE and IgA levels of asthmatic children with duration of disease of ≥4 yr were significantly higher than those with disease duration of <4 yr. IgA/IgE ratio was not significantly different in those two groups of asthmatics. We concluded that although all of the specific antibody levels increased with longer duration of asthma, IgA/IgE ratio remains to be low in asthmatic children allergic to HDM.

Characterization of the Cellular Response During Apoptosis Induction in Cadmium-Treated Hep G2 Human Hepatoma Cells

Cadmium is a toxic transition heavy metal of continuing occupational and environmental concern, with a wide variety of adverse effects on regulation of gene expression and cellular signal transduction pathways. Injury to cells by cadmium leads to a complex series of events that can culminate in the death of the cell. It has been reported that cadmium induces apoptosis in many cell lines. However, the morphological characteristics leading to apoptosis or subsequent regeneration in cells exposed to cadmium have not been clarified.We evaluated whether human hepatoma cells maintained in culture undergo apoptosis when exposed to cadmium. Cytotoxic activity of cadmium on Hep G2 cells determined using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. A DNA ladder assay was performed by electrophoresis. Cell cycle analysis was quantified by flow cytometry. Nuclear morphology was studied by fluorescence microscopy after staining with propidium iodide and Hoechst 33342. Morphologic alterations in culture hepatocytes treated with CdCl2 were observed by transmission electron microscopy.We have demonstrated that apoptosis is a major mode of elimination of damaged HepG2 cells in cadmium toxicity and it precedes necrosis.

Sensitization to cat allergens in non–cat owner patients with respiratory allergy

BACKGROUND Cats represent one of the most important sources of indoor allergens. The sensitization rate can reach up to 60% in western countries. Keeping cats indoors is uncommon in big cities in Turkey, but cats living in the streets are common. OBJECTIVE To investigate the prevalence of sensitization to cats in patients with respiratory allergy from Izmir, Turkey, and its relationship to home cat allergen levels. METHODS A total of 387 patients (70.8% female; mean age, 34.3 years) with respiratory allergic diseases (rhinitis and/or asthma) were included in this study. Skin prick test to cat was performed. House dust samples were collected from the living room of 25 patients and 14 healthy subjects. The major cat allergen (Fel d 1) levels were measured by Dustscreen. Fel d 1 levels given by the manufacturer were as follows: 0.05, 0.13, 0.40, 1.1, and 6.2 mU/mL. RESULTS The prevalence of cat sensitivity was 44.7% (n = 173). Only 6 patients (1.6%) had a history of feeding a cat in their houses. Thirty-six (92%) of 39 houses had detectable levels of cat allergen (mean Fel d 1 level, 2.24 +/- 2.69 mU/mL). The mean Fel d 1 levels were 1.58 +/- 2.51 mU/mL in the healthy group, 1.91 +/- 2.61 mU/mL in the asthmatic group, and 3.26 +/- 2.85 mU/mL in the group with allergic rhinitis (P = 0.12). The prevalence of cat sensitivity in patients who had 1.1 mU/mL of Fel d 1 in their homes was 57.1%. This rate was five times lower (11.1%) in patients who had the highest Fel d 1 level (6.2 mU/mL) in their homes. CONCLUSIONS The prevalence of cat sensitivity in Izmir, where cats are generally not kept within homes, is as high as in western countries. The sampled houses have measurable levels of Fel d 1 even in the absence of indoor cats. High prevalence of cat sensitivity in Izmir is probably due to indirect exposure.

The determinants of bronchial hyperresponsiveness in patients with allergic rhinitis

BACKGROUND Patients with allergic rhinitis and bronchial hyperresponsiveness (BHR) may be at higher risk of developing asthma. OBJECTIVE To investigate whether reactivity to aeroallergens in skin prick testing (SPT) and serum eosinophil cationic protein levels can be used to predict BHR in allergic rhinitis patients. METHODS Fifty-nine consecutive patients with allergic rhinitis underwent SPTs using grass, tree, weed, parietaria, Alternaria, Aspergillus, mites, and cat and dog dander extracts. Methacholine challenge tests were performed using spirometry. RESULTS Methacholine-induced BHR was detected in 23 patients (39%). Of 59 patients, 14 had 1 positive SPT response, 35 had 2 to 4 positive responses, and 10 had more than 4 positive responses. There was a significant inverse correlation between methacholine provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% (PC20) and the number of positive SPT responses (r = -0.28; P = .03). The BHR-positive patients had a mean of 4 positive SPT responses, whereas BHR-negative patients had a mean of 2.6 (P = .04). Nine BHR-positive patients (39%) and only 1 BHR-negative patient (3%) had more than 4 positive SPT responses (P < .001). There was no correlation between serum eosinophil cationic protein levels and methacholine PC20 doses. There was a strong association between hyperresponsiveness to methacholine and both cat and dog dander sensitivity (P < .001 and P = .001, respectively). CONCLUSIONS Allergic rhinitis patients with SPT responses to a higher number of allergens are more likely to have BHR. Whether the number of positive SPT responses correlates with the risk of developing asthma in allergic rhinitis patients remains to be determined.

Chlamydia pneumoniae arthritis in a patient with common variable immunodeficiency

BACKGROUND Arthritis is an important and sometimes life-threatening complication in patients with common variable immunodeficiency (CVID). OBJECTIVE To describe a patient with CVID and arthritis due to Chlamydia pneumoniae, which is usually regarded as a respiratory tract pathogen and has not previously been detected in the synovial fluid by cell culture technique. METHODS Routine bacteriologic, virologic, mycologic, and tuberculosis cultures were performed. The patients synovial fluid was examined for fastidious organisms that might be causative pathogens of arthritis, such as chlamydiae, and special cell culture methods were used. Serologic tests were performed to determine viral and bacteriologic etiology. RESULTS The patient had a history of recurrent respiratory tract infections, and the latest exacerbation was followed by arthritis. Cytologic examination of the fluid yielded abundant lymphocytes. Chlamydia pneumoniae was detected in synovial fluid specimens by cell culture technique. Her nasopharyngeal swab and sputum culture specimens were also positive for this pathogen. She was diagnosed as having arthritis caused by C pneumoniae and was given antibiotherapy. CONCLUSION Chlamydia pneumoniae should be kept in mind as a causative pathogen in patients with CVID and arthritis, especially when effusion fluid is full of lymphocytes rather than polymorphonuclear cells and no organism is grown on routine cultures.

House dust mite allergens in Turkish homes

Exposure to house dust mites (HDMs) is a major risk factor for allergic sensitization and asthma (1). Assessing HDM allergen exposure at home is critical to evaluate risk factors for sensitization and can play a role in controlling environmental factors that contribute to asthma severity (2). Although it is reported that the predominated HDM was Dermatophagoides pteronyssinus in Turkish homes (3), data on mite allergen levels has never been reported. Therefore, we aimed to investigate HDM allergen levels of homes in Izmir, the third populated city in Turkey situated next to Aegean Sea and to identify predictors of dust mite allergen concentration. Dust samples were obtained from 25 homes of allergic patients with perennial symptoms, consecutively referred to our out patient clinic for the first time for their allergies. Fourteen healthy subjects served as a control group. House dust samples were collected from an area of 1 m with a 1200-W, filtered vacuum cleaner. Dust mite allergen (Der p 1 and Der f 1) concentration was determined by Dustscreen assay, a method easier to perform and as satisfactory as enzyme-linked immunosorbent assay (4). The HDM allergen levels were expressed as lg/m. The minimum detection level of Der p 1 and Der f 1 was 0.1 lg/m. Independent predictors of allergen concentration were assessed. Either Der p 1 or Der f 1 was detected in 21 of 39 homes (53.8%). Dermatophagoides pteronyssinus predominated in most of the houses (71.4%). Twentythree percent of houses were coinhabited by D. farinae and D. pteronyssinus. Der p 1 was detected in twenty houses in the range of 0.4–5.4 lg/m (median 2). We observed Der p 1 >2 lg/m of dust in 55% of the houses. Whereas Der f 1 was detected in only six houses (median 1, range 0.1–6.4 lg/m). Der p 1 levels were significantly higher in allergic subjects houses than healthy controls (median 2 vs 0.4 lg/m, P 1⁄4 0.041). Twenty-one of 25 allergic subjects (84%) were sensitive at least to D. farinae or D. pteronyssinus assessed by skin prick test. Independent predictors of higher levels were evidence of moisture, such as mildew or water stains in the home and residency at seaside. In conclusion, more than half of the houses in Izmir had detectable levels of dust mite allergen. Dermatophagoides pteronyssinus was the most frequently found species. Allergic patients encountered more HDM allergens than normal subjects in their home, and this situation may emphasize the importance of environmental factors in the development of allergic diseases. Indoor moisture and residency at seaside were predictors of higher mite allergens.

Diagnostic value of specific IgE analysis in latex allergy.

Background: The precision of the methods used to diagnose latex allergy is of great importance due to false-positive results. Neither the skin prick test (SPT) nor the latex-specific IgE assay has 100% diagnostic accuracy. We analysed the diagnostic value of latex-specific IgE by the first-ever concomitant use of the SPT and nasal provocation test (NPT). Methods: Twenty-seven latex-sensitive patients (group 1), 46 aeroallergen-sensitive patients (group 2a) and 33 healthy subjects (group 2b) participated in the study. All groups underwent an SPT with latex and aeroallergens and an NPT with latex. Latex-specific IgE and total IgE levels were measured by the ImmunoCAP assay. Results: Latex-specific IgE was positive in 92.6, 30.4 and 9.1% of groups 1, 2a and 2b, respectively. The 11 aeroallergen-sensitive patients in group 1 and all of the patients in group 2a were predominantly sensitised to pollens (grass, weed and tree) and reacted to a lesser degree to house dust mite, moulds and animal dander. Combined pollinosis was remarkably more prevalent in patients with positive latex-specific IgE in group 2a than in those with negative latex-specific IgE (p = 0.001). The NPT was positive in 84.6% of group 1 and negative in all control subjects. The sensitivity, specificity, negative predictive value and positive predictive value of the latex-specific IgE assay were 90.9, 72.2, 96.3 and 50%, respectively. Conclusion: The high rate of false-positive results for latex-specific IgE by ImmunoCAP should be taken into account when making a diagnosis of latex allergy in patients with pollinosis, especially in those sensitised to more than one pollen species.

The importance of nasal provocation test in the diagnosis of natural rubber latex allergy.

Background:  Most studies regarding natural rubber latex (NRL) allergy have concentrated on the prevalance using skin prick test (SPT) and specific IgE assay. The objective of this study is to examine the target organ (skin, nasal mucosa) responses in patients with positive SPT to NRL using the nasal provacation test (NPT) and glove use test (GUT).

Vitamin D deficiency in the absence of enteropathy in three cases with common variable immunodeficiency.

Background: Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and a defect in antibody production. Herein we describe 3 patients diagnosed with CVID in whom vitamin D deficiency was detected in the absence of enteropathy. Methods: Biochemical and immunological analysis, serum osteocalcin, parathyroid hormone, 25-OH vitamin D, 1,25(OH)2 vitamin D, vitamin A, vitamin E, urinary calcium, and deoxypyridinoline measurements were carried out. Vitamin D receptor (VDR) expression was examined in the peripheral blood mononuclear cells and hair follicles by reverse transcriptase polymerase chain reaction. VDR gene polymorphism was evaluated by high-performance liquid chromatography. Results: None of the patients presented nutrient deficiencies other than vitamin D. Two of them were free of osteomalacia-related symptoms. VDR expression was found to be lower in the peripheral blood mononuclear cells and hair follicles when compared to the control group. Conclusions: Patients with CVID may present asymptomatic vitamin D deficiency. Vitamin D and VDRs play an important role in the innate immune system and modulate Toll-like receptor-related responses. Delay in diagnosis may predispose these patients not only to irreparable bone loss but also to infections, and autoimmune and malignant disorders, thus emphasizing the importance of prompt intervention.