IgE Levels In Patients Research Articles

Interleukin-4 genetic variants correlate with its transcript and protein levels in patients with vitiligo

Vitiligo is an acquired pigmentary disorder resulting from loss of melanocytes. Interleukin (IL)-4 has been shown to stimulate B-cell proliferation, to regulate immunoglobulin class switching (IgG1 and IgE) and to promote T-cell development. Polymorphisms in the IL4 gene are known to increase its expression, thereby implicating its role in vitiligo susceptibility. To explore intron 3 VNTR (IVS3) and -590 C/T (rs2243250) promoter polymorphisms in the IL4 gene and to correlate them with the IL4 transcript, serum IL-4 and IgE levels to achieve genotype-phenotype correlation in patients with vitiligo from Gujarat. A replication study was done in a North Indian population. The case-control study was performed to investigate these polymorphisms in 505 patients and 744 controls in Gujarat, and 596 patients and 397 controls in North India by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism analysis. IL4 transcript levels were monitored by real-time PCR. Serum IL-4 and IgE levels were measured by enzyme-linked immunosorbent assay and electrochemiluminescence immunoassay, respectively. The genotype frequencies differed significantly between patients with generalized vitiligo and controls for both the polymorphisms in both populations. Allele frequencies significantly differed between patients with generalized vitiligo and controls for both the polymorphisms in the population from Gujarat. Interestingly, genotype and allele frequencies for -590 C/T single nucleotide polymorphism were significantly different between patients with localized vitiligo and controls in both the populations. The study revealed significantly increased IL4 mRNA, serum IL-4 and IgE levels in patients from Gujarat. Age of onset analysis of disease in patients suggested that the TTR2R2, TTR1R2 and CTR2R2 haplotypes had a profound effect in the early onset of the disease. Our results suggest that these polymorphisms of the IL4 gene may be genetic risk factors for susceptibility towards vitiligo and the upregulation of the IL4 transcript, protein and IgE levels in individuals with susceptible haplotypes reveal the crucial role of IL-4 in the pathogenesis of vitiligo.

Polymorphisms of STAT6 and specific serum IgE levels in patients with penicillin allergy

Signal transducer and activator of transcription (STAT) 6 signaling pathway is required for mediating the biologic functions of interleukin (IL)-4 which is proved to play an important role in the pathogenesis of allergic diseases and the induction of specific immunoglobulin (Ig) E synthesis. The current studies are conducted to evaluate the relationship between polymorphisms of STAT6, specific IgE and penicillin allergy. In 242 patients with penicillin allergy and 220 controls, polymorphisms of STAT6 in2SNP3 and 3'UTRSNP3 were genotyped by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). Eight kinds of specific IgE to penicillins were detected with radioallergosorbent test (RAST). For STAT6 in2SNP3, the frequency of the CC genotype was significantly higher in all patients than in controls (60 vs. 47%, p = 0.005). A similar result was observed between patients of the urticaria group and controls (70 vs. 47%, p = 0.005). With respect to allele frequency, the C-allele occurred more frequently in all patients and in the urticaria group than in controls (78 vs. 69%, p = 0.002; 83 vs. 69%, p = 0.007). Our finding suggests that STAT6 in2SNP3 is associated with penicillin allergy, but has no effect on the specific IgE levels of patients with penicillin allergy.

473 Evaluating Total Serum IgE Levels in Patients with Chronic Hepatitis B and C

BackgroundLiver disease has been considered a prominent cause of IgE elevation. Significant differences may be observed depending on the cause of liver damage. For viral hepatitis, increased IgE concentrations have been observed during acute hepatitis A and B. Chronic hepatitis B carriers may also have high IgE levels. But no data on serum IgE levels in chronic hepatitis C and hepatitis B patients have been reported. The aim of the study was to evaluate serum IgE levels in patients with chronic hepatitis C and hepatitis B and to corelate with atopic patients.MethodsSerum IgE levels were determined in 568 adult patients with chronic hepatitis B, in 47 patients with chronic hepatitis C, and 311 patients with atopic diseases.ResultsThe averages of serum IgE levels were 103,9 IU/mL in chronic hepatitis C, 95,1 IU/mL in hepatits B patients, and 126,6 IU/mL in atopic patients. There was no statistically significant difference between hepatits B and hepatits C patients. Total serum IgE levels were lower in patients with either chronic hepatitis C or hepatitis B than the atopic group.ConclusionsAccording to the results presented, chronic hepatitis C and hepatitis B are not prominent causes of increased serum IgE values. Further studies are needed to clarify the differences and significance of IgE levels between hepatitis and atopic patients.

295 Association of Feno with IgE Levels in Patients with Allergic Asthma

BackgroundAsthma is a chronic multifactorial disease characterized by inflammation with multiple triggers. Inflamation of the airways is the main pathologic pathway in asthma, and not only determines the diagnosis and severity of symptoms, but is also useful to establish treatment and predict potential complications. By measuring FeNO levels, an indirect level of pulmonary inflammation can be obtained since it is produced by alveolar macrophages in response cytokines. One of the main known causes of this inflammatory response is an allergic reaction. This allergic reaction sets off a cascade of biochemical events that leads to the expression of inflamatory mediators, preformed or de novo, and IgE being the principal of such mediators. The objective was to evaluate the relationship between levels of FeNO and IgE to inflammation and allergy severity.Methods50 patients (72% female and 28% male) aged 12 to 50 years old, diagnosed with asthma were taken from the Allergy and Immunology department. A complete medical history was performed, and the diagnosis was confirmed through a clinical history and spirometric criteria, according to GINA 2010. All medications that could alter the inflammatory process were taken away for 15 days. Lastly, total serum IgE levels were measured with electrochemiluminescence technique and the FeNO with standard procedures. The data was further analyzed using a Pearson's correlation test.Results21% of the participants showed normal IgE values (<100 UI/Ml) and 33% of the participants had normal FeNO measurements (<20 ppm). A 0.29 coefficient was measured using a Pearson's correlation test, which suggests a low positive correlation between the 2 observed variables.ConclusionsThe results showed a low correlation between the IgE and FeNO levels. This result does not allow for a correlation between both parameters; which leads to a conclusion that high levels of IgE from an allergic reaction is not necessarily going to lead to a high FeNO, thus a pulmonary inflammation. Additionally, it emphasizes the importance of the allergists and pneumonologists to work together when treating an asthma patient, given the multidisciplinary nature of this pathology.

A Study on the Serum Immunoglobulin Levels in Pulmonary Tuberculosis Patients

Tuberculosis is a severe bacterial infection caused by Mycobacterium tuberculosis. In the recent years, studies on the immunological diagnosis of tuberculosis have become advancing. In this study, forty patients diagnosed with tuberculosis on the basis of history, clinical examination, chest radiography, sputum examination and related laboratory parameters were recruited from The Institute of Thoracic Medicine, Chennai, India and were compared with age and sex matched healthy volunteers (n=35). The Serum immunoglobulins IgA, IgM, IgE levels were determined in 40 patients with pulmonary tuberculosis. IgA, IgM, IgE, levels were found to be increased significantly (p<0.001) when compared with normal healthy volunteers. The rise of IgA, IgM, IgE levels in patients with tuberculosis may be interpreted as humoral response to mycobacterial antigens.

Polymorphisms of the CYP2C19 gene in Japanese patients with aspirin-exacerbated respiratory disease

Polymorphisms of the CYP2C19 gene in Japanese patients with aspirin-exacerbated respiratory disease

A Clinical Study on Serum IgE Levels in Patients with HIV Infection

A Clinical Study on Serum IgE Levels in Patients with HIV Infection

Elevated Serum Total IgE – A Potential Marker for Severe Chronic Urticaria

Background: Elevated IgE levels in patients with chronic urticaria have been noted previously, but the significance of these findings has not been appreciated. Objective: To measure the IgE levels in such patients and to examine the relationship between these levels and urticarial severity, autologous serum skin test, anti-thyroid antibodies and duration. Methods: Serum total IgE levels from 203 patients with chronic urticaria were measured and compared with nonatopic individuals. Additionally, patients were assessed for urticarial severity, the presence of autologous serum skin test and anti-thyroid antibodies. Results: Of the chronic urticaria patients, 47 (23.2%) were classified as mild, whereas 67 (33%) were classified as having moderate and 89 (43.8%) as having severe chronic urticaria. Total IgE levels were elevated, above 175 U/ml, in 69/203 (34%) of patients, compared with 7/81 (8.6%) of healthy controls (p < 0.001). A significant association between increased total IgE and chronic urticaria severity was found. Whereas 93% of patients with increased level of total IgE suffered from moderate-to-severe chronic urticaria, this was observed in only 69% of patients with normal IgE (p < 0.0001). Autologous serum skin test and anti-thyroid antibodies were positive in 59/163 (36%) and 28/189 (15%) patients, respectively. A significant association between increased total IgE levels and the presence of autologous serum skin test, anti-thyroid antibodies and urticarial duration lasting more than 25 months (p < 0.0001, p < 0.0001 and p = 0.021, respectively) was also detected. Conclusions: Total serum IgE levels are frequently elevated in patients with chronic urticaria and these are associated with disease severity and duration.

Incrimination of Blomia tropicalis as a Potent Allergen in House Dust and its Role in Allergic Asthma in Kolkata Metropolis, India

Background Theincreasing trend in allergic diseases has become obvious in the present day, especially in developing countries like India, because of many factors such as change in ambient air quality, increased air pollution, metamorphic change in living habits and lifestyle, and climate 1. Mites present in house dust represent a major source of allergens, resulting in different allergic manifestations all over the world, and hypersensitivity to these dust mites may play a pivotal role in pathogenesis of several allergic complaints including bronchial asthma. The present study evaluated the sensitization toward house dust and house dust mites among patients residing in Kolkata metropolis, India, who are suffering from allergic asthma.Methods The skin prick test was performed on a total of 1079 patients (585 males and 494 females) between the age group 5-50 years and 50 healthy controls using a variety of 16 common aero-allergenic extracts including 4 allergens of interest, viz. Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Blomia tropicalis and total house dust allergens. Total serum IgE level was measured by using the EIA technique and specific IgE levels against aforesaid allergens were detected with the Pharmacia ImmunoCAP 100 System. The influence of age and sex, if any, on allergen sensitivity was also investigated. All statistical analyses were performed using SPSS 10.0 for Windows and Zar 2.Results The responses among patients with asthma to house dust and house dust mite allergen tests were as follows: house dust (96.22%), D. pteronyssinus (75.06%), B. tropicalis (72%), and D. farinae (63.72%). The frequency of positive skin response was found to be independent of age and sex. The total serum IgE levels in patients varied between 7.3 and 4040 IU/ml (mean 369 ± 26.51 IU/ml). Specific IgE antibody test proved that 83% patients showed sensitivity toward at least 1 of the allergens tested.Discussion The results indicate that patients are highly sensitive to house dust and 3 other allergenic mites, namely, D. pteronyssinus, D. farinae, and B. tropicalis, as evidenced by the skin prick test, quantification of total serum IgE, and detection of allergen-specific IgE antibodies among patients of Kolkata. Although mites belonging to the genus Dermatophagoides have already been incriminated as a major source of allergen in house dust in India, this is the first time the role of B. tropicalis mites causing allergic asthma has been reported from an Indian population. Thus, the importance of B. tropicalis mite as an aetiopathological agent in causing various allergic manifestations among the Kolkata population should not be undermined and the allergen should be included in routine allergy testing.

The level of immunoglobulin E in patients with pyoinflammatory diseases

Object. Cause-and-effect relations^ assessment of immunoglobulin E leveTs increase in patients with pyoinplammatory diseases. Materials and methods. 80 patients with acute appendicitis, 51 patients with chronic recurrent furunculosis, 27 patients with chronic osteomyelitis aged 16 to 60 years old have been examined. The patients with the increased IgE level underwent clinical and allergologycal assessment. Patients with chronic pyoinplammatory diseases had been skin tested with the Staphylococcus aureus allergens. Results. Total IgE level was increased in all nosologic groups of patients. In patients with the increased IgE level atopy or antihelminths antibodies have been established. In patients with chronic pyoinflammatory total IgE level was not changed but negative correlative connections between the level of immunoglobulin and the late phase of immediate hypersensitivity reaction have been shown. Increased level of serum immunoglobulin E in patients with acute appendicitis confirmed more serious involvement of appendix and surrounding tissues and the higher indexes of white blood cells count before the operation. Conclusion. Increased IgE level in patients with pyoinflammatory diseases reflects Th2 type of immune response mostly due to the condition of atopy or parasites. The higher rate of development of destructive and complicated forms of appendicitis is typical for the patients with acute appendicitis and the increased IgE level.

Serum mast cell tryptase is not a useful marker for disease severity in psoriasis or atopic dermatitis

Severity in psoriasis and atopic dermatitis (AD) is commonly assessed with the Psoriasis Area and Severity Index (PASI) and the SCORing Atopic Dermatitis (SCORAD), respectively. Until today no serum marker is available to reflect the clinical scoring in both diseases. As mast cells play an important role in the pathogenesis of early psoriasis and AD, tryptase, a major compound of mast cell granules that is released upon activation, could in principle serve as such a marker. To assess the correlation between serum tryptase and severity of psoriasis and AD as well as the correlation between total IgE levels and severity of AD. Serum samples from patients hospitalized for psoriasis and AD were collected at time of admission and time of discharge from hospital. PASI and SCORAD assessments were performed at the same time points. Outpatients presenting with naevi and other benign noninflammatory skin lesions served as control group. Serum tryptase values and total IgE levels of patients with AD were measured using a fluoroenzyme immunoassay technique. No correlation of serum tryptase level with either the severity of psoriasis or the severity of AD was seen. Total IgE levels in patients with AD at time of admission and discharge from hospital remained the same. Serum total tryptase did not prove to be a useful tool in assessing severity of psoriasis or AD. Total IgE levels did not correlate with severity of AD.

Does Atopy Affect the Radiological Extent of Pulmonary Tuberculosis?

BackgroundTh1 cytokines, IL-2 and IFN-γ, have critical importance in the CD4 cell driven antimycobacterial activity. Th2 type immune response is a characteristic feature of atopic disorders. Th1 and Th2 cells have been reported to negatively cross-regulate each other in vitro and in experimental animals. Our aim in the present study is to determine whether the atopy affects radiological extent of pulmonary tuberculosis (TB) and disease severity. Materials and methodsA total of 82 male patients with pulmonary TB were prospectively enrolled in the study between March 2005 and March 2006. All patients were evaluated for atopic symptoms and TB related systemic symptoms. Radiological dissemination was scored and cavitation was noted. The skin prick test (SPT) was performed and serum total IgE level was measured. ResultsThe SPTs were positive in 28 of 82 (34.1 %) patients. There was no distinction between SPT-positive and negative patients in terms of pulmonary cavitation and radiological dissemination. The median IgE level of moderate-severe radiologically disseminated TB patients was significantly higher than that of mild radiologically disseminated TB patients (130 IU/ml vs. 58 IU/ml). Cavitary TB patients had also significantly higher median IgE levels (78 IU/ml vs. 46 IU/ml) (p < 0.05) ConclusionThis study suggests that SPT-positivity and atopic respiratory phenotype do not affect the formation of cavitation, radiological dissemination and systemic symptoms of pulmonary TB. The high level of IgE in patients with cavitary and radiologically disseminated TB may be a consequence of a dysregulated immune response to infection or reflect disease activity.

Association of the expression of IL-4 and IL-13 genes, IL-4 and IgE serum levels with allergic asthma.

Immune and inflammatory responses mediated by cytokines, play important roles in the pathophysiology of asthma. These responses are associated with overexpression of Th2 cytokines such as IL-4 and IL-13. These two cytokines use common receptors for signaling that lead to identical immunological effects and regulation of the Th1/Th2 balance. The aim of this study was to determine whether patients with allergic asthma display overexpression of IL-4 and IL-13 genes. Using RT-PCR, we examined the expression of IL-4 and IL-13 genes in twenty asthmatic cases and twenty normal individuals. Total levels of serum IgE and IL-4 were also determined by ELISA method. Expression of IL-13 gene in 70% of patients with allergic asthma was higher than controls (P=0.01). There was no correlation between the expression of IL-13 gene and total level of serum IgE (P=0.07). Expression of IL-4 gene was detected in 30% of the patients and none of the normal individuals as determined by RT-PCR (P=0.01). Mean of serum IgE levels in patients and controls were 84.9 IU/ml and 62.2 IU/ml, respectively. Level of serum IgE was more than 100 IU/ml in 30% of patients (P=0.03). Mean of serum IL-4 levels in patients and controls were 15.73 pg/ml and 13.07 pg/ml, respectively. There was a relation between levels of serum IgE and IL-4 in 73% of cases. The results showed that there was a correlation between the expression of IL-4 gene and the level of serum IL-4. Levels of serum IgE and IL-4 were considerably higher in asthmatics than non-asthmatic controls.

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 >or=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.

Determination of mRNA Expression and Serum Levels for IL-4 and IL-13 in Asmathic Patients

INTORDUCTION: Immune and inflammatory responses that mediated by cytokines play an important relo in the pathophisiology of asthma. These responses are associated with over expression of Th2 cytokines such as IL-4 and IL13. These two sytokines use shared receptors for signaling that lead to identical immunological effects and the requlation of the Th1/Th2 balance. The aim of this study was to determine whether patients during asthmatic attack had over-expression of IL-4 and IL-13 genes. MATERIALS AND METHODS: Using RT-PCR, we examined IL4 and IL-13 mRNA gene expression in twenty asthmatic cases and twenty healty individual who had not symptoms or history of asthma and other allergic disease. Extracted mRNA form activated PBMCs of one healthy control with PHA is used as positive control. Total serum IgE and IL-4 level were determined by ELISA Method. RESULTS: IL-13 mRNA expression in 70% of patients during asthmatic attack increased in resoect to control (p-value=0.01) but no correlation exist between IL-13 mRNA and total serum IgE (p-value=0.0708). Thirty percent of patients had IL-4 gene expression by RT-PCR(P=0.01), but none of controls had IL-4 gene expression. Mean serum IgE level in patients and in normal indiciduals were 84.9 IU/ml and 62.2 IU/ml (p=0.01) respectively. Thirty percent of patients had IgE level greater than 100 IU.ml (p=0.01). There was correalation between serum IgE and IL-4 in 73% of cases. CONCLUSION AND DISCUSSION: The results showed that, there is some correlation betweem IL-4 gene expression and serum IL-4. All results indicate that serum IgE and IL-4 concentratin is considerably higher in asthmatics than non-asthmatic controls. There is a correlation between IL-4 gene expression and IL-4 glycoprotien in serum as a gene product. IL-13 mRNA expression in 70% of patients during asthmatic attack increased in respect to cintrols. Eventually, this study provides additional evidence that Th2 cytokines (IL-13, IL-4) gene expression play a key role in the imbalance of Th1/Th2 in asthmatic patients; but the role of IL-13 in more significant. KEY WORDS: Asthma, IL-4, IL-13, RT-PCR.

Both Th1 and Th2 chemokines are elevated in sera of patients with autoimmune blistering diseases

Although chemokines are critical elements for the selective attraction and activation of various leukocyte subsets in the inflammatory process, there are few findings concerning T helper (Th) 1 or Th2 chemokines in autoimmune blistering disease (ABD). To determine whether serum levels of chemokines that are preferentially chemotactic for Th1 (monokine induced by IFN-gamma (MIG/CXCL9)) and Th2 (thymus and activation regulated chemokine (TARC/CCL17) and macrophage derived chemokine (MDC/CCL22)) cells were elevated and whether they correlated with the clinical features in patients with ABD. Serum chemokine levels were examined using ELISA in patients with pemphigus vulgaris (PV, n=19), pemphigus foliaceous (PF, n=14), or bullous pemphigoid (BP, n=27) and normal controls (n=20). Serum MIG levels were significantly higher in patients with PV, PF, or BP than those in the control subjects. Serum levels of TARC and MDC were also significantly elevated in patients with PV, PF, or BP relative to the normal controls. Among the ABD subgroups, the levels of each chemokine tended to be higher in BP patients than in PV patients. Furthermore, serum TARC levels correlated positively with serum IgE levels in patients with ABD. Levels of TARC, MDC, and MIG were significantly decreased after treatment when the skin lesions disappeared in these patients. Furthermore, serum MIG levels correlated positively with serum levels of TARC and MDC in the ABD patients. These results suggest that both a Th1 chemoattractant MIG and Th2 chemoattractants, TARC and MDC, cooperatively play a role in the development of ABD.

Vitamin E effects on nasal symptoms and serum specific IgE levels in patients with perennial allergic rhinitis

Studies have shown that vitamin E intake may reduce IgE production. To evaluate the effects of vitamin E supplementation on the severity of nasal symptoms and the serum levels of specific IgE in patients with perennial allergic rhinitis. Sixty-three patients (mean +/- SD age, 12 +/- 2.4 years) with a history of perennial allergic rhinitis participated in this study. None of the patients had evidence of acute infectious disease or used tobacco, corticosteroids, antihistamines, or vitamins. Patients were randomized to receive either vitamin E (400 IU/d) or placebo for 4 weeks, with loratadine-pseudoephedrine (0.2/0.5 mg/kg) during the first 2 weeks of treatment. The severity of nasal symptoms was evaluated using a validated questionnaire, which was administered weekly for 4 weeks. The serum concentrations of specific IgE to 5 common inhalant allergens and lipid peroxides were measured before treatment and at the end of the study. Before, during, and after treatment, the symptom severity scores were similar in the 2 groups; within each group, a significant decrease was observed after the first week of follow-up (P < .05), with no further changes. Serum levels of specific IgE and lipid peroxides did not show any significant changes related to vitamin E intake within and between groups. In patients with perennial allergic rhinitis, vitamin E supplementation (400 IU/d) did not have any significant effects on nasal symptom severity or on serum concentrations of specific IgE to 5 common allergens.

Polymorphisms of IL–13 and IL–4–IL–13–SNPs in patients with penicillins allergy

Although IL-4 and IL-13 share many biologic activities, some are unique to IL-13. We genotype the IL-13 and IL-4-IL-13-SNPs genes for polymorphisms that could then be used to determine associations with IgE regulation as well as levels of IL-4 and IL-13. Eight kinds of IgE specific to penicillins were determined with radioallergosorbent test (RAST) in the sera of 158 patients with penicillin allergies and 89 healthy subjects. Serum levels of IL-4 and IL-13 were measured by using enzyme-linked immunosorbent assay (ELISA). The genotyping of IL-13Arg130Gln, IL-4-IL-13-SNP3 and IL-4-IL13-SNP4 was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Among patients with positive specific IgE, significant differences between the IL-4-IL-13-SNP3 and IL-4-IL-13-SNP4 genotypes were observed between patients with positive BPA and the control group (P<0.05, P<0.05). Additionally, we also found significant differences in the IL-4-IL-13-SNP4 genotype between positive and negative BPA-IgE patients (P<0.05). However, we found no significant differences in the prevalence of these polymorphisms between any of the symptomatic groups studied and the control group. Nor were there any significant differences between levels of IL-4 and IL-13 and any of genotypes. The data suggest that IL-4-IL-13-SNP genes between IL-4 and IL-13 play a role in regulation of specific IgE levels in patients with penicillin allergies.

Anti-Interleukin 6 Receptor Monoclonal Antibody Therapy Reduced Serum Interleukin 4 and IgE Production in Castleman's Disease.

Multicentric Castleman's disease (MCD) is an atypical lympho- proliferative disorder which is closely associated with dysregulated overproduction of interleukin-6 (IL-6). In the previous report, we showed that the humanized anti-IL-6 receptor monoclonal antibody, tocilizumab (formerly called MRA), was therapeutically effective for the patients with MCD and the safety profile was acceptable relative to the clinical benefit. We also found that serum IgE levels were elevated in some patients with Castleman's disease, which also decreased by IL-6 blocking therapy, suggesting that IL-6 may be involved in IgE production in vivo. To examine whether or not IL-6 serves as a regulator for IL-4, a major class switching factor for IgE, in vivo, we analyzed serum IL-4 as well as IgE levels in patients with MCD before and after the blockade of IL-6 actions utilizing humanized anti-IL-6 receptor monoclonal antibody in the 4-month clinical trial. Twenty-eight patients with MCD were enrolled and received intravenously 8 mg/kg of tocilizumab every two weeks for a total of 4 months. In fifteen of twenty-eight patients, 5–20 mg/day of prednisolone was used 4 weeks prior to study dosing, but the dosage of each patient was not changed during treatment. Serum IL-4 and IgE levels as well as inflammatory markers were monitored. This study complied with all provisions of the Declaration of Helsinki and was conducted in accordance with Good Clinical Practice guidelines. All patients gave written informed consent before participating in this study. Tocilizumab treatment improved the systemic inflammatory manifestations and laboratory markers such as CRP and fibrinogen as we previously reported. Before tocilizumab treatment, serum IL-4 and IgE levels were elevated (median 14.9 pg/mL, range 2.8–228 pg/mL and median 995 IU/mL, range 12–8000 IU/mL, respectively, n=28). Serum IL-4 levels gradually decreased by tocilizumab treatment (median 8.0 pg/mL, range 2.0–257 pg/mL at 6 weeks, n=28, p<0.005 vs. pretreatment; median 6.0 pg/mL, range 2.0–75.6 pg/mL at 16 weeks, n=28, p<0.0001, respectively). Serum IgE levels also significantly decreased at 6 weeks but not at 16 weeks (median 590 IU/mL, range 6–7000 IU/mL at 6 weeks, p<0.005; median 605 IU/mL, range 5.9–16000 IU/mL at 16 weeks, n.s, respectively). In association with the decrease in serum IL-4 and IgE levels, disease activity of atopic dermatitis improved in the patients with atopic dermatitis. IgE RAST scores for Japanese cedar also significantly decreased. IL-6 has been reportedly to direct the differentiation of IL-4-producing T helper cell 2 (Th2), in vitro, but the in vivo action of IL-6 has been controversial. Our findings clearly indicate that IL-6 regulates the IL-4 production, in vivo, and may serve as a regulator not only for B cell differentiation but also for class switching to IgE.

No Indication for a Defect in Toll-Like Receptor Signaling in Patients with Hyper-IgE Syndrome

Hyper-IgE syndrome is a rare primary immunodeficiency of unknown etiology characterized by recurrent infections of the skin and respiratory system, chronic eczema, elevated total serum IgE, and a variety of associated skeletal symptoms. Recent reports about susceptibility to pyogenic bacterial infections and high IgE levels in patients and animals with defects in toll-like receptor (TLR) signaling pathways prompted us to search for TLR signaling defects as an underlying cause of hyper-IgE syndrome. Blood samples from six patients with hyper-IgE syndrome were analyzed for serum cytokine levels, intracellular cytokine production in T cells after stimulation with PMA/ionomycin, and cytokine production from peripheral blood mononuclear cells stimulated by TLR ligands and bacterial products including LPS (TLR4), peptidoglycan (TLR2), PolyIC (TLR3), R848 (TLR7/8), CpG-A, and CpG-B (TLR9), zymosan and heat killed Listeria monocytogenes. All results were compared to data from healthy controls. A reduction in IFN-gamma, IL-2, and TNF-alpha producing T cells after PMA stimulation suggested a reduced inflammatory T cell response in patients with hyper-IgE syndrome. Increased serum levels of IL-5 indicated a concomitant Th2 shift. However, normal production of cytokines (TNF-alpha, IL-6, IL-10, IFN-alpha, IP-10) and upregulation of CD86 on B cells and monocytes after TLR stimulation made a defect in TLR signaling pathways highly unlikely. In summary, our data confirmed an imbalance in T cell responses of patients with hyper-IgE syndrome as previously described but showed no indication for an underlying defect in toll-like receptor signaling.