Recent developments in immunotherapy approaches for allergic rhinitis

Allergic rhinitis(AR)poses a significant global health burden,with the potential to progress to asthma,thereby impacting patients’quality of life.Immunotherapy has demonstrated effectiveness in mitigating clinical symptoms by altering the underlying disease mechanisms of AR.This article provides a thorough review of the current state of immunotherapy for AR,encompassing various facets of immunotherapeutic strategies,elucidating their mechanisms and clinical implications.By presenting a nuanced understanding of the present landscape of immunotherapy for AR,this review aims to serve as a valuable reference for informing clinical treatment strategies.The subsequent analysis of diverse immunotherapeutic pathways offers a comprehensive understanding of their mechanisms and clinical implications.A meticulous examination is conducted on subcutaneous immunotherapy,sublingual immunotherapy,oral immunotherapy,intralymphatic immunotherapy,and innovative intravenous gold-induced autologous serum injection therapy.Each pathway is systematically elucidated,with its distinctive features and potential contributions to managing AR emphasized.In conclusion,synthesizing epidemiological insights,immunotherapeutic nuances,and pathway-specific analyses encapsulates a profound understanding of immunotherapy for AR.

Unveiling childhood asthma:Exploring biomarkers,zinc,and beyond

This editorial discusses a case-control study by Ibrahim et al,published in the recent issue of the World Journal of Clinical Pediatrics.Childhood bronchial asthma is a chronic inflammatory respiratory disease.It was found that an increase in oxidative stress leads to a decrease in antioxidants causing oxidative damage to mitochondrial respiratory chain complexes resulting in the inflammation of the airway,hypersecretion of mucus causing a cascade of clinical manifestations ranging from recurrent episodes of coughing,wheezing,and breathlessness to shortness of breath.Since oxidative stress mediates the inflammatory response in asthma,the supplementation of anti-oxidants can be one strategy to manage this disease.Zinc is one such antioxidant that has attracted much attention about asthma and airway inflammation.Zinc is a crucial trace element for human metabolism that helps to regulate gene expression,enzyme activity,and protein structure.Apart from zinc,free serum ferritin levels are also elevated in case of inflammation.Several previous studies found that ferritin levels may also help determine the pathology of disease and predict prognosis in addition to tracking disease activity.However,this study's results were different from the findings of the previous studies and the zinc levels did not show a significant difference between asthmatic children and non-asthmatic children but ferritin levels were significantly high in asthmatic children as compared to the controls.Hence,the possible role of the biochemical nutritional assessment including zinc and ferritin as biomarkers for asthma severity should be assessed in the future.

鼻窦CT评分联合特异性免疫球蛋白E和白细胞介素6预测嗜酸粒细胞型慢性鼻窦炎伴鼻息肉患者术后复发风险的价值

目的探讨鼻窦CT评分联合特异性免疫球蛋白E(sIgE)和白细胞介素6(IL-6)对嗜酸粒细胞型慢性鼻窦炎伴鼻息肉(ECRSwNP)患者术后复发风险的预测价值。方法选取2019年1月~2022年1月浙江大学医学院附属杭州西溪医院收治的ECRSwNP患者92例,均行功能性鼻内镜手术,根据术后1年复发情况分为复发组(n=29)和未复发组(n=63)。比较两组鼻窦CT评分,并采用Pearson相关性分析法分析外周血嗜酸粒细胞(Eos)及组织Eos百分比(Eos%)与鼻窦CT评分的相关性;利用Logistic回归分析模型分析术后复发的危险因素,用受试者工作特征曲线(ROC)及曲线下面积(AUC)探究鼻窦CT评分、特异性免疫球蛋白E(sIgE)、IL-6对患者术后复发的预测价值。结果复发组前组筛窦评分、后组筛窦评分、鼻窦CT评分及筛窦与上颌窦评分比值(E/M比)均大于未复发组(P<0.05);组织Eos%与前组筛窦评分、后组筛窦评分及E/M比均呈正相关(r=0.305、0.381、0.642,P均<0.05),外周血Eos%与前组筛窦评分、后组筛窦评分及E/M比亦呈正相关(r=0.272、0.346、0.525,P均<0.05)。复发组哮喘患者占比、鼻塞视觉模拟量表(VAS)评分、组织Eos%、外周血Eos%及sIgE、IL-6水平均高于未复发组(P<0.05),组织中性粒细胞百分比(Neu%)、外周血Neu%则低于未复发组(P<0.05);Logistic分析显示,高水平血清sIgE、IL-6及高E/M比均是影响患者术后复发的危险因素(P<0.05)。ROC曲线分析显示,血清sIgE、IL-6、E/M比及三者联合预测ECRSwNP患者术后复发风险的AUC分别为0.818、0.758、0.696、0.915,三项指标联合预测效能高于单项检测(P<0.05)。结论高水平血清sIgE、IL-6及高E/M比是ECRSwNP患者术后复发的危险因素,三者联合预测患者鼻内镜术后复发风险具有较高临床价值。

Association Between IL-13 Gene Polymorphism and Asthma in Han Nationality in Hubei Chinese Population

Summary: In order to investigate whether Arg110Gln polymorphism in the coding region of the IL-13 gene is associated with asthma and total plasma IgE level in Han nationality in Hubei Chinese population, the allele frequency of 4257(g/a) site and Arg110Gln genotype of IL-13 was detected by using restriction fragment length polymorphism in Han nationality in Hubei Chinese population including 43 asthmatic children, 45 asthmatic adults, 31 control children and 46 control adults. Total plasma IgE was measured by Chemiluminescence assay. The results showed that the frequency of allele A at 4257 bp of IL-13 in children and adults was 0.39 and 0.32, respectively. The GlnGln form of Arg110Gln polymorphism of IL-13 gene was associated with susceptibility of asthma and elevated total plasma IgE in children (P =0.030 and 0.0009, respectively), but not with them in adults (P=0.219 and 0.174, respectively). Our results suggest that the Arg110Gln polymorphism of IL-13 gene is associated with susceptibility of asthma and elevated total plasma IgE in Chinese children of Han nationality in Hubei, but not with them in adults.

Experimental Researches on Inhibitory Effect of Huoxiang Zhengqi Liquid (藿香正气水) on Histamine Release

Objective: To observe the blocking effect of Huoxiang Zhengqi liqu id (HXZQL) on histamine release of basophils. Methods: The study was conducted using HXZQL to neutralize and b lock IgE and antagonize the effect of IL 3 induced enhancing histamine relea se of bosaphils. Concentration and percentage of histamine release of bosaphils were tested by the basophil histamine release test. Results: The HXZQL drug serum had obvious inhibitive effect on degranulation of bosaphils induced by IgE antigen antibody complex ( P <0.0 5) and can successfully weaken the histamine release of basophils stimulated by IL 3. When compared with those in the untreated group, it showed P <0.01. Conclusion: HXZQL drug serum may neutralize and block IgE and has inhibitive effects on degranulation of cells when resensitized by antigens. It can also block allergic response type Ⅰ by antagonizing the effect of IL 3 induced enhancing histamine release.

Molecular diagnosis in cat allergy

Domestic cats represent one of the most common sources of indoor allergens.All over the world,many households own cats,whose allergens are persistent and widespread.Cat allergy itself is frequent,and its symptoms vary from rhinoconjunctivitis to life-threatening asthma.In vitro diagnosis using precision medicine allergy immunoassays is important because natural cat dander extracts may differ in quality and quantity of some of the individual allergen components and other molecules.In the component-resolved diagnosis of cat allergy,singleplex and multiplex specific immunoglobulin(Ig)E assays include use of the cat-specific major allergen,secretoglobin Fel d 1(as a species-specific molecule),other allergen components(such as lipocalins Fel d 4,cross-reacting with other animal similar molecules,and Fel d 7,present in small quantities in natural extracts),and serum albumin Fel d 2(related to the cat-pork syndrome).IgA Fel d 5 and IgM Fel d 6 are not available as allergen components in the current commercial IgE immunoassays,but they may impair the in vitro diagnostic evaluation of cat allergy because galactose-α1,3-galactose is an IgE-binding epitope of these native feline allergens.The benefits of molecular-based cat allergy diagnosis are continually evaluated,as the role of recombinant allergen components already known is detailed and new other molecules of interest may be discovered in the future.

Oxaliplatin-Induced Lung Injury with Allergic Reaction

A 79-year-old man was diagnosed as stage IV colon cancer and treated with a modified FOLFOX6 （mFOLFOX6） regimen.On the 12th cycle,we observed erythema and dyspnea.Radiographs showed ground grass opacities.Blood tests showed elevated levels of eosinophils and immunoglobulin E.We diagnosed this finding as response to drug allergy and administered high-dose methylprednisolone.The treatment was successful and he was discharged.The drug lymphocyte stimulating test against oxaliplatin was positive,indicating a type I and IV allergic reaction due to oxaliplatin.Regimens including oxaliplatin must be carefully monitored and frequent blood tests and chest radiographs are needed.

Risk of connective—tissue disease in men with testicular or penile prostheses：a preliminary study

AIM: To help clarifying the possibility of connective-tissue diseases in men with penile or testicular prostheses. METHODS: Eight patients underwent inflatable penile prostheses and 15, testicular prostheses consented to the study. Their medical records were reviewed and a follow-up interview and physical and serological examinations were performed. RESULTS: In patients with penile prostheses, there was no abnormal antinuclear antibody (ANA) or IgM elevation. The serum levels of the rheumatoid factor (RF), C4, IgA and IgG were abnormal in one patient, and the levels of erythrocyte sedimentation rate (ESR) and C3, abnormal in two. Four had elevated IgE. In patients with testicular prostheses, there was no abnormal RF, ANA or IgM. The serum levels of ESR and IgA were abnormal in two, and three had abnormal C4, ten abnormal C3, and eleven decreased IgG. All had increased IgE. Men with penile prostheses had higher serum levels of IgG and IgM than those with testicular prostheses (P=0.001, P=0.016, respectively). The rates of abnormal values of IgE and IgG were higher in men with testicular prostheses than in men with penile prostheses (P=0.008, P=0.009, respectively). Physical examination was normal in all patients and nobody had documented symptoms pertinent to connective-tissue diseases. CONCLUSION: Our findings suggest that the risk of connective-tissue diseases is not higher in patients wearing prostheses as the ANA is negative and there is no apparent manifestation suggestive of connective-tissue diseases.

Effects of seasonal changes on T-helper 1/T-helper 2 immune balance and eczema onset in rats

Objective: To explore the impact of seasonal changes on the T-helper 1(Th1)/T-helper 2(Th2) immune balance of the body in order to elucidate the internal immunological mechanisms underlying seasonal eczema.Methods: Eighty 4-week-old male Sprague-Dawley rats were divided into 5 season groups kept in corresponding season simulation environments, and subdivided into the model group and the control group. The Eczema Area and Severity Index(EASI) and scratching frequency were evaluated. The serum levels of immunoglobulin E(IgE), interleukin-2(IL-2), interleukin-12(IL-12), and interferon-gamma(IFN-γ), interleukin-4(IL-4), interleukin-25(IL-25), and interleukin-31(IL-31), and melatonin(MT), as well as the MT receptor(MTR) levels in the spleen, were detected by enzyme-linked immunosorbent assay analysis. The mRNA expression levels of T-bet and GATA3 were detected by quantitative real-time polymerase chain reaction.Results: EASI scores and the scratching frequency of the model group were higher in the long summer than in the other 4 seasons. Meanwhile, the serum levels of IgE and the Th2 cytokines IL-4, IL-25, and IL-31, as well as GATA3 mRNA expression levels, were high during the long summer in both groups. However, the serum levels of the Th1 cytokines IL-2, IL-12, and IFN-γ, as well as MT, MTR, and T-bet mRNA levels, were lower during the long summer. In all 5 seasonal groups(spring, summer, long summer, autumn, and winter), the levels of all immune factors, especially IL-4 and IL-31, were higher in the model group than those in the control group,while the concentrations of MT and MTR were lower.Conclusion: Under long light, hot, and humid conditions in the long summer, the body is more likely to suffer from Th2-dominated immune imbalance. This is the internal mechanism behind the high incidence and severity of eczema during the long summer. MT and MTR play a key role in the seasonal onset of eczema.

Eczema herpeticum vs dermatitis herpetiformis as a clue of dedicator of cytokinesis 8 deficiency diagnosis:A case report

BACKGROUND Dedicator of cytokinesis 8(DOCK 8) deficiency,also known as autosomal recessive hyper immunoglobulin E(IgE) syndrome,is a combined immunodeficiency disease that was first recognized in 2009.It is caused by genetic alterations(mutations or deletions) in the DOCK 8 gene and is characterized by multiple allergies,elevated IgE levels,and susceptibility to viral and bacterial infections.Early diagnosis is critical to optimize the success of stem cell transplantation.CASE SUMMARY This study reports the case of a pediatric patient with DOCK 8 deficiency who had negative genetic testing using multiplex primary immunodeficiency(PID) panel and whole-exome sequencing(WES) with a next-generation sequencing method.He presented with chronic diarrhea and was managed as celiac disease based on previous negative workup for immunodeficiency and duodenal biopsy.He developed a generalized vesicular rash which was thought to be dermatitis herpetiformis associated with celiac disease.However,it turned out to be Eczema herpeticum based on positive herpes simplex virus from blood and lesions.The diagnosis was re-evaluated after the child was found to have multiple viral,bacterial,and parasitic co-infections(herpes simplex virus,cytomegalovirus,Epstein-Barr virus,Salmonella,and cryptosporidiosis).Re-evaluation with target gene testing with copy number variation(CNV) analysis and Multiplex Ligation Probe Amplification(MLPA) showed a large homozygous deletion in the DOCK 8 gene,confirming the diagnosis of DOCK 8 deficiency.CONCLUSION Targeted gene testing with CNV analysis might detect deletions that can be missed by WES for diagnosing patients with PID.

IgE PRODUCTION IS INVOLVED IN BUTYRATE- ENHANCED NK CELL ACTIVITY IN VIVO

It has been demonstrated that patients with asthma have a large number of NK cells and show a stronger NK activity. These results indicate that NK cell activity may be related to total IgE level in serum in healthy subjects. Previously,we have found that sodium butyrate (NaBu) markedly enhanced the IL- 4- induced IgE production in the LPS- stimulated murine splenocytes in vitro, and inductive rat IgE production in vivo, and enhanced the NK cell activity ex vivo .We hypothesized that the IgE production might be involved in butyrate- enhanced NK cell activity in vivo. Mice were intraperitoneally treated/immunized with NaBu or/and Ascaris suum extract (ASC),and the spleen NK cell activity was evaluated. Furthermore, the effect of serum (NAS) on IL- 2- or IFN-γ- induced spleen NK cell activity was determined. The spleen NK cell activity and IL- 2- or IFN-γ- induced spleen NK cell activity of mice treated/immunized with NaBu or/and ASC were stronger than those of untreated/unimmunized mice. Although IL- 4 blocked IL- 2 (100 U/ml)- or IFN-γ (100 U/ml)- induced increase in NK cell activity,these NK cell activities in mice treated/immunized with NaBu/ASC were not inhibited. IgE production showed a tendency to rise in NaBu- treated mice serum, and a synergistic effect was observed with treatment of NaBu and ASC. Moreover, the NAS significantly increased IL- 2(25 U/ml)- or IFN-γ (25 U/ml)- induced NK cell activity, and its effect was inhibited by anti- mouse IgE mAb. These data show that IgE plays an important role in NAS- enhanced IL- 2/IFN-γ- induced NK cell activity, and IL- 4 does not inhibit IgE and IL- 2/IFN-γ- induced NK cell activity in mice.

Prediction of antigenic determinants of trichosanthin by molecular modeling

The antigenic determinants of trichosanthin were predicted by molecular modeling. First, the threedimensional structure model of the antigen-binding fragment of anti-trichosanthin immunoglobulin E was built on the basis of its amino-acid sequence and the known three-dimensional structure of an antibody with similar sequence. Secondly, the preferable antigen-antibody interactions were obtained based on the known three-dimensional structure of trichosanthin and of the hypervariable regions of anti-trichosanthin immunoglobulin E. Two regions in the molecular surface of trichosanthin were found to form extensive interactions with the hypervariable regions of the antibody and have been predicted to be the possible antigenic determinants: one is composed of two polypeptide segments, Ile201-Glu210 and Ile225-Asp229, which are close to each other in the three-dimensional structure; and the other is the segment Lys173-Thr178. The former region seems to be the more reasonable antigenic determinant than the latter one.

Clinical Observation of Chuanbai Antipruritic Lotion"Water Film"Wet Compress Combined with Chloramphenicol Prednisone Liniment in the Treatment of Acute Eczema

[Objectives]To observe and analyze the clinical efficacy and possible mechanism of Chuanbai antipruritic lotion"water film"wet compress combined with chloramphenicol prednisone liniment in the treatment of acute eczema.[Methods]A total of 76 acute eczema cases admitted to Shiyan Taihe Hospital from January 2022 to March 2023 were divided into Western medicine treatment group and integrated traditional Chinese and Western medicine group.In the Western medicine treatment group,chloramphenicol and prednisone liniment was applied to the skin lesions and oral administration of cetirizine hydrochloride.The course of treatment in both groups was 2 weeks(w).The levels of interferon-γ(IFN-γ),interleukin-4(IL-4)and the ratio of IFN-γ/IL-4 in the peripheral blood of patients before and 2 weeks after treatment,as well as serum immunoglobulin E(IgE),anti-IgE antibody and histamine(HA)level,and with skin lesions disappearing time,skin oil,transepidermal water loss(TEWL),eczema area and severity index(EASI)score,total effective rate,degree of pruritus and traditional Chinese medicine quality of life scale(EPQOLS)score to evaluate the efficacy.[Results]Compared with the Western medicine treatment group at 2 w,the disappearance time of skin lesions in the integrated traditional Chinese and Western medicine group was shortened,TEWL,itching degree and EASI score,serum IgE and HA,and peripheral blood IL-4 levels were all decreased(P<0.05).IFN-γand IFN-γ/IL-4 ratio,anti-IgE antibody,EPQOLS score and total effective rate were all increased(P<0.05),and the difference was statistically significant.[Conclusions]Chuanbai antipruritic lotion"water film"wet compress combined with chloramphenicol prednisone liniment is an optimized and safe and efficient method for the treatment of acute eczema,which can quickly relieve the symptoms of inflammatory damage of eczema and restore the skin barrier function,dry dampness and relieve itch.Inhibition of the release of histamine active substances and regulation of immunity may be the main mechanisms.

In Silico Analysis of the Cross-Reactivity of Pacific White Shrimp (Litopenaeus vannamei) Allergens with Other Arthropod Species

This study provided new data in the area of cross-reactivity for Pacific white shrimp (Litopenaeus vannamei). Although the cross-reactivity between the most prominent allergenic proteins of shrimp and other crustaceans has been extensively studied, few data are showing the frequency of arthropod-shrimp Litopenaeus vannamei cosensitization in an in silico analysis. A comparative analysis of “typical and non-typical” shrimp L. vannamei allergens with other species was achieved, revealing new allergens and previously characterized shrimp allergens, which validated the comprehensive identification approach used in this study. Importantly, up to 192, amino acid sequences were identified that had matches to shrimp L. vannamei allergens that matched allergenic proteins in mites, insects, fish, bacteria, mammals, birds, and plants.

Food allergy in children-the current status and the way forward

Food allergy in children is a major health concern,and its prevalence is rising.It is often over-diagnosed by parents,resulting occasionally in unnecessary exclusion of some important food.It also causes stress,anxiety,and even depression in parents and affects the family’s quality of life.Current diagnostic tests are useful when interpreted in the context of the clinical history,although cross-sensitivity and inability to predict the severity of the allergic reactions remain major limitations.Although the oral food challenge is the current gold standard for making the diagnosis,it is only available to a small number of patients because of its requirement in time and medical personnel.New diagnostic methods have recently emerged,such as the Component Resolved Diagnostics and the Basophil Activation Test,but their use is still limited,and the latter lacks standardisation.Currently,there is no definite treatment available to induce life-long natural tolerance and cure for food allergy.Presently available treatments only aim to decrease the occurrence of anaphylaxis by enabling the child to tolerate small amounts of the offending food,usually taken by accident.New evidence supports the early introduction of the allergenic food to infants to decrease the incidence of food allergy.If standardised and widely implemented,this may result in decreasing the prevalence of food allergy.

Topical Application of Cudrania tricuspidata Stem Extract Inhibits Atopic Dermatitis-Like Skin Lesions in an NC/Nga Mouse Model: An Experimental Animal Study

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by elevated immunoglobulin E (IgE), mast cell infiltration and skin lesions including pruritus, erythema and eczema. Cudrania tricuspidata extracts have been clinically administered for a long time in the East Asia including Korean and China as a home-remedy to diminish the inflammation of gastritis and hepatitis. To examine whether it works on AD or not, an AD-like animal model was experimented in this study. AD was induced by applying Dermatophagoides farinae (D. farinae) extract to the backs of 9-week old NC/Nga mice for 21 days. Following this, an ethanol extract of C. tricuspidata stems (EECT) was applied topically for 14 days to the sensitized skin, while distilled water was used as a control (EECT0 mice). Anti-AD effects of EECT were evaluated using scores for AD-like skin lesions, serum IgE levels and mast cell counts in the skin dermal layers to assess inflammation. Topically applied ethanol extract of Cudrania tricuspidata stems (EECT 7.5, 25 and 75 mg/mL) markedly reduced AD-like skin lesions after 4 days (by 30.1%, 31.4% and 38.5%, respectively) and also after 14 days (by 63.6%, 66.1% and 49.6%, respectively), while distilled water improved AD by 17.8% and 38.7%, respectively (p D. farinae extract (p = 0.003) and EECT attenuated the mast cell overproduction, and reduced mast cell degranulation markedly. Attenuation was most obvious in the early stage of EECT treatment when the AD was most acute.

Generalized prurigo nodularis with dramatic response to dupilumab treatment: A case report

BACKGROUND Prurigo nodularis(PN)is a chronic condition characterized by a papulonodular pruriginous eruption of unknown aetiology.Currently,there are no medications for PN that the United States Food and Drug Administration has approved,which leads to very variable practices in the prescription of off-label treatments.Treatment of PN is based on clinical experience rather than controlled trials.We present our case of generalized PN,in which we had a dramatic response with dupilumab.CASE SUMMARY A 58-year-old female patient was admitted to our clinic with severe itchy,erythematous nodular lesions that were widespread all over her body,especially on the legs and back.It was learned that the patient's complaints started 4 years ago,and there was a significant increase in the lesions in the last period.Dermatological examination revealed diffuse firm erythematous excoriated nodular lesions all over the body.In the blood tests of the patient,serum Immunoglobulin E(IgE)was measured at 9330 IU/mL.The patient was diagnosed with generalized prurigo nodularis together with clinical and histopathological findings.Due to severe clinical findings and the presence of comorbidities,dupilumab treatment was planned for the patient.In the follow-up 4 mo later,it was observed that all nodular lesions healed with postinflammatory hypopigmentation.The IgE value decreased to 1500 IU/mL after 4 mo of dupilumab treatment.CONCLUSION Dupilumab treatment stands out as an effective and safe systemic treatment agent among existing systemic treatments.

Treatment with Enterococcus faecalis CECT7121 Is Not Effective as Therapy in Mice with an Established Allergy Status

In allergies, an unbalanced immune response towards a T helper (Th) 2 profile with high levels of Immunoglobulin (Ig) E is produced. We have demonstrated that the pre-administration of Enterococcus faecalis CECT7121 prevents the development of allergy in ovalbumin-immunized mice. In this work, we evaluated whether this bacterium can also revert an established allergic status. Mice were immunized with ovalbumin (OVA) and after that, were inoculated with an E. faecalis CECT7121 suspension. In immunized animals, serum specific immune response, proliferative activity of memory splenocytes, and levels of Th2 cytokines were assessed. The in vivo active cutaneous anaphylaxis test was also performed. The treatment with E. faecalis CECT7121 only increased anti-OVA IgG2a levels. No differences were observed in other specific immunological parameters. Probiotic-treatment did not prove to have any desensitizing effect on mice. These results, together with those recently published, can be concluded that this bacterium would not be appropriate for the treatment of allergic symptoms.

30 and 32 kDa outer membrane proteins of Bordetella pertussis as a modulator on promoting degranulation of mast cells

The correlation between the activities of the outer menbrane proteins （OMPs） of Bordetella pertussis and the lgE-mediated asthma was investigated in the present study, in which the OMPs of B. pertussis and their components were prepared by detergent treatment and chromatography, and the molecular weights of the OMPs components were determined by SDS-PAGE. The amounts of total as well as the ovalbumin （OVA）-specific IgE induced by dead B. pertussis whole bacterial vaccine on guinea pigs were detected by ELISA. Meanwhile, the effect of the OMPs and their components to promote the degranulation of guinea pig mast cells was observed by using the mast cell degranulation test, and ELISA assay was used to measure the histatmine levels in the supematants from the mast cell cultures. Histamine sensitive test was used to demonstrate the effects of the OMPs and their components to increase the histamine lethal sensitivity in mice. It was found that four components with molecular weights of 30, 32, 38 and 69 kDa could be obtained from the OMPs of B. pertussts, and the dead whole bacteria vaccine of B. pertussis had the ability to increase the levels of the total as well as the OVA-specific IgE in sera of guinea pigs. The OMPs and their 30 and 32 kDa components demonstrated significantly enhancing effect on the degranulation of guinea pig mast cells, and the histamine levels in the supematants from the mast cell culture treated with OMPs and their 30 and 32 kDa components were also significantly increased. It is evident that the strong adjuvant activity and the enhancing effect to degranulation of mast cells and the release of histamine of certain outer membrane components of B. pertussis could be demonstrated as revealed by the results of the present study, suggesting the possibility of a close relationship between the infection of vaccination with B. pertussis and the IgE-mediated asthma.

Antibody-Like Phosphorylation Sites in Focus of Statistically Based Bilingual Approach

In accordance with previous reports, the sequences related to phosporylated protein segments occur in conserved variable domains of immunoglobulins including first of all certain N-terminally located segments. Consequently, we look here for the sequences 1) composing human and mouse proteins different from antigen receptors, 2) identical with or highly similar to nucleotide sequence representatives of conserved variable immunoglobulin segments and 3) identical with or closely related to phosphorylation sites. More precisely, we searched for the corresponding actual pairs of DNA and protein sequence segments using five-step bilingual approach employing among others a) different types of BLAST searches, b) two in-principle-different machine-learning methods predicting phosphorylated sites and c) two large databases recording existing phosphorylation sites. The approach identified seven existing phosphorylation sites and thirty-seven related human and mouse segments achieving limits for several predictions or phylogenic parameters. Mostly serines phosporylated with ataxia-telangiectasia-related kinase (involved in regulation of DNA-double-strand-break repair) were indicated or predicted in this study. Hypermutation motifs, located in effective positions of the selected sequence segments, occurred significantly less frequently in transcribed than non-transcribed DNA strands suggesting thus the incidence of mutation events. In addition, marked differences between the numbers and proportions of human and mouse cancer-related sequence items were found in different steps of selection process. The possible role of hypermutation changes within the selected segments and the observed structural relationships are discussed here with respect to DNA damage, carcinogenesis, cancer vaccination, ageing and evolution. Taken together, our data represent additional and sometimes perhaps complementary information to the existing databases of empirically proven phosphorylation sites or pathogenically important spots.