Injection Of Antigen Research Articles

Comparative study of intralesional tuberculin protein purified derivative (PPD) and intralesional measles, mumps, rubella (MMR) vaccine for multiple resistant warts.

Cutaneous warts are frequent conditions that possess much challenge to treat. To evaluate safety and efficacy of intralesional injection of tuberculin purified protein derivative (PPD) antigen injection vs MMR (mumps, measles, rubella) antigen for the treatment of multiple warts. The study included 90 Patients who were divided into three groups (A, B, and C). Each group consisted of (30) patients. Group (A) subjects received intralesional PPD injections. Group (B) subjects received intralesional MMR antigen injection and Group (C) received intralesional saline injection. Full clearance of warts was observed in 18 (60%) of patients in group (A) (70%) vs 24 patients (80%) in group (B). Distal warts completely disappeared in 18 (60%) of patients in group A and 12 (40%) of patients in group B. Infrequent side effects including pain, erythema, and minimal induration were reported in both groups. We established a good safety and efficacy profile for tuberculin PPD and MMR antigens in resistant wart treatment.

Therapeutic vaccination against leukaemia via the sustained release of co-encapsulated anti-PD-1 and a leukaemia-associated antigen.

Therapeutic leukaemia vaccines have shown modest potency. Here, we show that the co-encapsulation of a leukaemia-associated epitope peptide highly expressed in leukaemia patients and of the immune checkpoint inhibitor anti-programmed-cell-death-protein-1 (anti-PD-1) in degradable poly(lactic acid) microcapsules resulted in the sustained release of the peptide and of the antibody, which led to the recruitment of activated antigen-presenting cells to the injection site, their uptake of the peptide and the transportation of the anti-PD-1 antibody to lymph nodes, enhancing the expansion of epitope-specific T cells and the activation of cytotoxic T cells. After single subcutaneous injections of vaccine formulations with different epitope peptides, mice bearing leukaemia xenografts derived from humanized cell lines or from primary cells from patients showed better therapeutic outcomes than mice receiving repeated injections of free antigen, antibody and a commercial adjuvant. The sustained release of a tumour-associated peptide and of anti-PD-1 may represent a generalizable strategy for boosting antitumour immune responses to leukaemia.

Evaluation of intralesional Candida antigen in diabetic patients with multiple warts.

Treatment of warts in diabetic patients with ablative modalities poses a significant risk owing to increased possibility of secondary infection, slow healing, and recurrence. Intralesional immunotherapy has gained popularity in the treatment of warts due to its proven efficacy and good tolerability compared with destructive methods. To evaluate the intralesional Candida antigen injection for the treatment of multiple warts in diabetic patients. Fifty diabetic patients with multiple genital/nongenital warts were divided into two groups. The first group (30 patients) received intralesional Candida antigen, and the second group (20 patients) had intralesional saline as control. The treatments were injected into the largest wart every 2weeks until complete clearance of warts or for a maximum of five sessions. Complete clearance of warts was observed in 80% of the diabetic patients in the Candida antigen group compared with 15% in the control group (P<.001). Side effects to Candida antigen included pain during injection in all patients, flu-like symptoms, and localized reaction at the injection site in few patients. Intralesional Candida antigen injection can be a promising effective and safe therapeutic option for the treatment of warts in diabetic patients.

Abstract 5563: Harnessing pre-existing viral immunity for development of a broadly applicable tumor immunotherapy

Abstract The availability of high throughput DNA sequencing provides an opportunity to generate a potent immune stimulation against unique antigens expressed by tumors. Although such approaches have led to increased immune responses in certain individuals, it is often limited to a small patient population and is associated with high development and implementation costs. Therefore, there is an unmet need for an immunotherapy that is easy to manufacture at affordable cost and applicable across many different tumor types. Here, we propose a unique approach to leverage pre-existing anti-Human Cytomegalovirus (CMV) immunity using a defined cocktail of viral epitopes, to both directly kill the tumor cells and induce a secondary T cell response to tumor neoantigens. We chose to recruit CMV immunity because CMV infection is highly prevalent, reaching approximately 90% of the population by the age of 80 years, and because of the naturally-occurring inflation of anti-CMV T cell responses with age leads to high levels CMV-specific T cells. Consequently, in elderly individuals, CMV-specific T cells recognizing a limited number of viral epitopes constitute approximately 10% of all systemic CD4 and CD8 T cells, a level rarely achieved by conventional vaccination. Additionally, in contrast to other chronic viral infections, CMV-specific T cells remain highly functional. In our experimental model, mice persistently infected with Murine Cytomegalovirus (mCMV) were subcutaneously challenged with TC-1 tumor cells (expressing human papillomavirus E6 and E7 oncogenes) or colon adenocarcinoma MC38 tumor cells, followed by intratumoral injections of mCMV peptide antigens together with a Toll-like receptor 3 (TLR3) agonist poly(I:C). Intratumoral injection of mCMV MHC-I or MHC-II restricted epitopes alone led to local and systemic recall of mCMV-specific T cells, and a potent local immune activation resulting in complete rejection of TC-1 and MC38 tumors in a subset of animals. Coinjection of both MHC-I and MHC-II peptides resulted in complete tumor clearance is most animals. Clearance was associated with antigen spreading, as evidenced by protection from secondary tumor challenge and ex vivo IFN-gamma ELISPOT responses to tumor-specific epitopes. Our preclinical studies provide a proof of concept of a first-in-class tumor antigen-agnostic immunotherapy based on recruitment of pre-existing antiviral T cells. The approach induced rapid tumor regression, profound changes in the tumor immune environment, epitope spreading, and resulted in long-term tumor protection. We are currently investigating the contribution of other cell types including NK cells and B cells to the anti-tumor effect of our approach. Citation Format: Nicolas Cuburu, Lukas Bialkowski, Sergio M. Pontejo, Alexander Bell, Rina Kim, Cynthia D. Thompson, Douglas R. Lowy, John T. Schiller. Harnessing pre-existing viral immunity for development of a broadly applicable tumor immunotherapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5563.

Pengaruh Injeksi Multi Antigen terhadap Pertambahan Berat Badan, Bobot Organ Relatif dan Profil Eritrosit pada Puyuh Jantan (Coturnix coturnix japonica) Usia 5 Bulan

Coturnix coturnix japonica is one of quail the promising commodities to breding. Health management of poultry in livestock such as quail has problems related to the threat of disease from the environment. Diseases caused by disease agents attack birds resulting in morbidity and mortality so that farmers experience losses. This study aims to determine the effect of injection of two different antigens at different time frames on body weight gain, relative organ weight and erythrocyte profile in 5-month-old male quail. The study used an experimental method of completely randomized design (RAL) with animals as many as 28 male quails divided into 7 groups with 4 replications, namely K0: not injected with antigen, P1: injection SDMD 2%, P2: SDMD injection 2% and ND vaccine, P3 : injection ND and SDMD 2% in week 4, P4: injection vaccine ND, P5: injection SDMD 2% and SDMD 2%, P6: injection treatment ND vaccine and injection ND vaccine. Data obtained by body weight gain, relative organ weight, erythrocyte count, hemoglobin level and hematocrit value. Data were analyzed by Analysis of Variance (ANOVA) using MiniTab17. The results showed that organ weight gain, relative organ weight, heart, heart, pancreas, kidney, lung, spleen, erotrocyte count, hemoglobin level, and hematocrit value were not significantly different (P&gt; 0.05) with control treatment so it can concluded that the effect of antigen injection does not affect the weight gain of organs, the relative weights of the liver, heart, pancreas, kidney, lungs, spleen, the number of erotrosites, hemoglobin levels, and hematocrit values.

Combined oral isotretinoin and Candida antigen versus either agent alone in the treatment of plane warts

Background Oral isotretinoin and intralesional immunotherapy by Candida antigen have shown promising efficacy and safety for the treatment of plane warts in a few studies. Objective To evaluate the efficacy and safety of a combination of oral isotretinoin and Candida antigen versus either agent alone in the treatment of multiple plane warts. Methods The study included 108 patients who were randomly assigned to three groups, 36 in each. Group 1 received oral isotretinoin alone at a dose of 0.3 mg/kg/day. Group 2 received intralesional injection of Candida antigen alone at a dose of 0.1 ml of 1/1000 solution into the largest wart. Group 3 received a combination of Candida antigen and oral isotretinoin by the same method and dose mentioned above. Results Complete clearance of warts was observed in 44.4% of the oral isotretinoin alone group, in 55.6% of the Candida antigen alone group, and in 38.8% of the combination therapy group. A statistically significant difference in favor of the Candida antigen alone group was demonstrated. Conclusions Candida antigen, oral isotretinoin and a combination of both represent potential effective and safe modalities for the treatment of plane warts, with the Candida antigen alone as the most effective.

Abnormal gut microbiota composition is associated with experimental autoimmune prostatitis-induced depressive-like behaviors in mice.

Depressive symptoms are found in approximately 78% of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) patients, but the pathological mechanisms remain unknown. Increasing evidence suggests that abnormal gut microbiota may play an important role in depression. Thus, we aimed to investigate whether gut microbiota contributes to CP/CPPS-associated depression by using a mouse model of experimental autoimmune prostatitis (EAP). Male nonobese diabetic mice were immunized twice by subcutaneous injection of prostate antigen and adjuvant. Behavioral tests consisted of an open field test, sucrose preference test, forced swimming tests, and tail suspension test was used to confirm the depression-like symptoms that were induced by EAP. Then, fecal samples were collected, and 16S ribosomal RNA gene sequencing was performed to detect differences in gut microbiota composition between control and EAP group. Additionally, fecal bacteria from the control and EAP mice were transplanted into antibiotics-induced pseudo-germ-free mice to investigate the effects on host behaviors and the composition of gut bacteria. EAP was successfully established and exhibited depressive-like behaviors in mice. The 16S rRNA analysis of fecal samples indicated the abnormal composition of gut microbiota in the EAP mice compared to the control mice. In the fecal microbiota transplant study, antibiotics-treated pseudo-germ-free mice presented depressive states as compared to naïve mice. Fecal bacteria transplant from EAP mice, but not from control mice, into the pseudo-germ-free mice, significantly exaggerated host depression-like behaviors. Moreover, fecal bacteria transplants from control and EAP mice induced distinct alterations in α-diversity and β-diversity indices. In all, 24 bacteria at six phylogenetic levels were remarkably changed by the fecal bacteria transplantation. Abnormal gut microbiota composition after EAP induction may contribute to the development of depression in mice. A therapeutic strategy that targets gut microbiota may provide an alternative treatment for alleviating this condition.

Early Metabolic Syndrome (MetS) in Chronic Rhesus Macaque Model of Human Allergic Asthma

Human asthma, obesity, MetS, overt Type 2 diabetes, and related sequelae such as cardiovascular diseases, account for much of the mortality and morbidity worldwide. The etiology and complex physiological mechanisms underlying these pathological states intersect within the human body – and within Rhesus macaques. Much like humans, these animals (in captivity) often develop spontaneous, age‐related obesity. Hence, these animals are ideally suited for investigations of obesity and metabolism, as well as chronic allergic asthma.In 2013, twenty animals were sensitized by i.p. injection of house dust mite antigen (HDM) adsorbed to alum; airway sensitization and maintenance were accomplished by exposure to aerosolized HDM (aeroHDM) at ≥ 2‐week intervals, to a dose that induced an acute asthmatic response: ≥ 100% increase in lung resistance, ≥ 40% decrease in dynamic compliance, and/or peripheral oxygen saturation ≤ 70%. Periodically, we assessed the late phase asthmatic response 24 hours after aeroHDM exposure: airway hyperreactivity was assessed by aerosolized methacholine challenge; pulmonary inflammation was assessed by bronchoalveolar lavage. Occasionally animals were also exposed to an experimental asthma therapeutic.In 2018, ten animals had developed obesity and were suspected to harbor other clinical manifestations of MetS. Retrospective analyses confirmed relative hypertension in animals that had robust responsiveness to aeroHDM and were &gt; 16 kg. Using archived frozen serum samples, we reconstructed the biochemical history of adiposity development and glucose metabolism ‐ a story that was evolving coincident with chronic exposures to both Diet A and aeroHDM (Fig. 1). By age 10 years, 4/5 of the largest animals (body weight, 21 ± 2 kg; waist circumference in lateral recumbency, 68 ± 5 cm; BMI using crown‐to‐rump length, 53 ± 3 kg/m2: values are mean ± SD) had insulin resistance (peak HOMA‐IR, 61 ± 29) associated with leptin &gt; 14 ng/ml and total adiponectin &lt; 3.5 μg/ml; 3/5 animals had dyslipidemia (Fig. 2); 1/5 animals had diabetes by age 8 years – 4 to 6 years earlier than would be expected based on non‐human primate literature. Biomarkers of inflammation and oxidative stress are outstanding.In July 2019, six months after switching to lower carbohydrate/higher protein Diet B, and &gt; 12 months since the last aeroHDM exposure: all animals lost weight coincident with larger animals resolving insulin resistance, dyslipidemia, and diabetes. As seen in some obese asthmatic humans, larger animals had higher pulmonary inflammation (especially neutrophilic) and higher airway hyperreactivity to aerosolized methacholine.We concluded that chronic allergic inflammation synergized with inflammation of developing adiposity, accelerating onset of MetS in susceptible animals. We hypothesize that resumption of chronic periodic aeroHDM exposure will trigger more rapid progression/re‐establishment of MetS, IR, and eventually overt Type 2 diabetes if we do not intervene.Historical event timeline.Figure 1Body weight and serum triglycerides of 5 largest animals (mean ± SD: n=3 to 5 for each time point). Gray vertical bar: gradual transition to lower carbohydrate/higher protein Diet B.Figure 2

Association of TLR2 and TLR4 gene polymorphism with susceptibility to wart infections and their response to candida antigen immunotherapy

Background Warts are prevalent human papilloma virus (HPV) infections which can cause physical and psychological problems. Candida antigen immunotherapy is a safe and promising treatment of warts. Toll-like receptors (TLRs) 2 and 4 gene polymorphisms are implicated in susceptibility and progression of several diseases. Aim To assess the role of TLR2Arg753GLN and TLR4Asp299Gly polymorphisms in susceptibility to HPV wart infections and their possible effect on response to Candida antigen immunotherapy. Patients and methods A total of 78 patients and 78 healthy subjects were enrolled in this case control study. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to detect TLR2Arg753GLN and TLR4Asp299Gly genes polymorphisms. Patients’ lesions were injected with Candida antigens and the response was assessed. Results The mutant AA and GG genotypes of TLR2Arg753GLN and TLR4Asp299Gly were significantly detected in patients than controls (p < .001 and p = .01, respectively). Intralesional Candida antigen injections achieved complete and partial clearance in 62.8 and 20.5% of lesions, respectively. No association was found between the studied polymorphisms and response to Candida antigen injections. Conclusions TLR2Arg753GLN and TLR4Asp299Gly polymorphisms are associated with susceptibility to wart infections, but with no effect on their response to Candida immunotherapy.

Sustained-immunostimulatory nanocellulose scaffold to enhance vaccine efficacy.

An implantable scaffold-based vaccination system is a promising platform to generate robust immune responses by modulating the immune system. However, establishment of an effective vaccine using a biodegradable, cell-infiltrative scaffold remain challenging. Here we demonstrate a biodegradable, nanocellulose-based immune scaffold capable of sustainably activating immune cells to elicit cellular immunity. Cell-infiltrative nanocellulose hydrogels were used as a delivery carrier and cellular scaffold microenvironment. Nanofibrous hydrogels allowed for high cell infiltration and delivery of antigen-loaded nanocellulose while cells degraded the hydrogel matrix. Importantly, antigen-loaded nanocellulose hydrogels exhibited sustained activation of macrophages in vitro compared to free antigen and collagen scaffold. Histological observation revealed infiltration of macrophages and dendritic cells into the nanocellulose scaffold subcutaneously implanted in mice. In vivo fluorescence imaging indicated that the implanted scaffold released antigens at a zero-order release profile without burst diffusion. Antigen-loaded nanocellulose hydrogels increased interferon-γ-producing cells compared to free antigen injection, suggesting the enhancement of cellular immunity. Thus, nanocellulose immune scaffold may serve as a sustained-immunostimulatory vaccine platform by providing favorable microenvironments for immune cells thus enhancing vaccine efficacy.

Intravitreal thalidomide ameliorates inflammation in a model of experimental uveitis induced by BCG

Uveitis encompasses a heterogeneous and complex group of conditions characterized by intraocular inflammation, frequently affecting young individuals and representing an important cause of irreversible blindness worldwide. Animal models have been critical to understand etiology and pathogenesis of uveitis, being also employed to assess new therapeutic strategies, preceding human studies. However, there is still a need of developing and studying different models, due to the difficulties in recapitulating all forms of human uveitis effectively. Although corticosteroids are usually the first-line therapy for non-infectious uveitis, their long-term use is limited by potentially serious side effects in all possible delivery routes. Thus, thalidomide, a drug with anti-inflammatory and antiangiogenic properties, was investigated in a novel experimental model of uveitis, induced by Mycobacterium bovis Calmette-Guérin Bacillus (BCG), in rabbits. The experimental protocol consisted of two subcutaneous injections of BCG, followed by two intravitreal injections of the same antigen, inducing panuveitis. Animals were treated with a single intravitreal injection of thalidomide suspension or PBS. Clinical manifestations of uveitis improved after intravitreal thalidomide, involving both anterior and posterior segments. Protein content, N-acetyl-b-glucosaminidase (NAG) and myeloperoxidase (MPO) activities were elevated in ocular tissues after disease induction, further decreasing post-treatment with intravitreal thalidomide. This therapeutic response was also confirmed on ocular electrophysiology, as well as histopathology. This experimental model induced panuveitis in rabbits using a low-cost mycobacterial antigen, with intraocular inflammation subsequently improving after treatment. Intravitreal thalidomide may be a potential alternative to treat intraocular inflammation in corticosteroid-sparing therapies.

Chronic inflammation promotes proliferation in the prostatic stroma in rats with experimental autoimmune prostatitis: study for a novel method of inducing benign prostatic hyperplasia in a rat model

ObjectiveInflammation plays an important role in the development of benign prostatic hyperplasia (BPH). The aim of the present study was to reference the study of the pathological changes in the prostate gland of rats with experimental autoimmune prostatitis (EAP), for the development of experimental models of BPH.MethodsExperimental autoimmune prostatitis was induced in rats by the intradermal injection of rat prostate antigen with immunoadjuvants. In case of the positive BPH group, BPH was induced by the subcutaneous injection of testosterone propionate. At the end of the 45-day model period, prostate weights were measured, and the histopathological analysis of the prostate glands was performed. The levels of cytokines, TGF-β1/RhoA/ROCK signals, and the oxidative stress status were also examined.ResultsRats from the EAP group had a higher histological score than those from the control group. Compared to the samples from rats in the hormone-induced group, those from the EAP group showed a more pronounced increase in the size of the stromal compartment; this was characterized by the formation of reactive stroma and the deposition of a greater amount of extracellular matrix (ECM). Significant increases in the numbers of CD3-positive cells and CD68-positive cells, as well as a significant upregulation in the cytokine levels, and an increase in the TGF-β1 levels and activation of RhoA/ROCK signaling, were observed in the samples from rats in the EAP group.ConclusionChronic inflammation can induce BPH in rats via EAP model method. When performing drug experiments on the stroma compartments of BPH, the use of the EAP model is a recommendation of the authors based on this study.

Sensory Ganglia-Specific TNF Expression Is Associated With Persistent Nociception After Resolution of Inflammation.

Joint pain is a distressing symptom of arthritis, and it is frequently persistent even after treatments which reduce local inflammation. Continuous production of algogenic factors activate/sensitize nociceptors in the joint structures and contribute to persistent pain, a challenging and difficult condition to treat. TNF is a crucial cytokine for the pathogenesis of several rheumatic diseases, and its inhibition is a mainstay of treatment to control joint symptoms, including pain. Here, we sought to investigate the inflammatory changes and the role of TNF in dorsal root ganglia (DRG) during persistent hypernociception after the resolution of acute joint inflammation. Using a model of antigen-induced arthritis, the peak of joint inflammation occurred 12–24 h after local antigen injection and was characterized by an intense influx of neutrophils, pro-inflammatory cytokine production, and joint damage. We found that inflammatory parameters in the joint returned to basal levels between 6 and 8 days after antigen-challenge, characterizing the resolving phase of joint inflammation. Mechanical hyperalgesia was persistent up to 14 days after joint insult. The persistent nociception was associated with the inflammatory status of DRG after cessation of acute joint inflammation. The late state of neuroinflammation in the ipsilateral side was evidenced by gene expression of TNF, TNFR2, IL-6, IL-1β, CXCL2, COX2, and iNOS in lumbar DRG (L3-L5) and leukocyte adhesion in the lumbar intumescent vessels between days 6 and 8. Moreover, there were signs of resident macrophage activation in DRG, as evidenced by an increase in Iba1-positive cells. Intrathecal or systemic injection of etanercept, an agent clinically utilized for TNF neutralization, at day 7 post arthritis induction, alleviated the persistent joint hyperalgesia by specific action in DRG. Our data suggest that neuroinflammation in DRG after the resolution of acute joint inflammation drives continuous neural sensitization resulting in persistent joint nociception in a TNF-dependent mechanism.

Anti-EGF antibodies as surrogate biomarkers of clinical efficacy in stage IIIB/IV non-small-cell lung cancer patients treated with an optimized CIMAvax-EGF vaccination schedule

ABSTRACT We previously reported that CIMAvax-EGF vaccine is safe, immunogenic and efficacious to treat advanced non-small-cell lung cancer (NSCLC) patients. A phase III trial was designed using an optimized immunization schedule. It included higher antigen dose and injections at multiple sites. Immune response and circulating biomarkers were studied in a subset of patients. EGF-specific antibody titers, IgG subclasses, peptide immunodominance and circulating biomarkers were assessed by ELISA. In vitro EGF-neutralization capacity of immune sera and EGF-IgG binding kinetics was evaluated by Western Blot and Surface Plasmon Resonance (SPR) technology, respectively. We show that CIMAvax-EGF elicited mainly IgG3/IgG4 antibodies at titers exceeding 1:4000 in 80% of vaccinated patients after 3 months of treatment. The EGF-specific humoral response was directed against the central region of the EGF molecule. For the first time, the kinetic constants of EGF-specific antibodies were measured evidencing affinity maturation of antibody repertoire up to month 12 of vaccination. Notably, the capacity of post-immune sera to inhibit EGFR phosphorylation significantly increased during the course of the immunization scheme and was related to clinical outcome (P = .013, log-rank test). Basal concentrations of EGF and TGFα in the serum were affected by EGF-based immunization. In conclusion, the CIMAvax-EGF vaccine induces an EGF-specific protective humoral response in a high percent of NSCLC vaccinated patients, the quantity and quality of which were associated with clinical benefit (clinical trial registration number: RPCEC00000161, http://registroclinico.sld.cu/). Abbreviations EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; Ab: antibody; AR: amphiregulin; NSCLC: non-small-cell lung cancer; rhEGF: recombinant human epidermal growth factor; BSC: best supportive care; TGFα: tumor growth factor alpha; IL-8: interleukin 8; MAb: monoclonal antibody; SPR: surface plasmon resonance

Rapid desensitization of humanized mice with anti-human FcεRIα monoclonal antibodies

Anaphylaxis is classically mediated by allergen cross-linking of IgE bound to the α chain of FcεRI, the mast cell/basophil high affinity IgE receptor. Allergen cross-linking of the IgE/FcεRI complex activates these cells, inducing release of disease-causing mediators, cytokines, and enzymes. We previously demonstrated that IgE-mediated anaphylaxis could be safely prevented in wild-type BALB/c mice by rapid desensitization with anti-mouse FcεRIα mAb. This study sought to use humanized mice to extend these results to humans. We actively immunized huFcεRIα/F709 mice, which express human (hu) instead of mouse FcεRIα and a mutant IL-4 receptor that lacks inhibitory function. We passively immunized huFcεRIα mice, as well as human cord blood-reconstituted reNSGS mice, which are immune-deficient, produce mast cell-stimulating human cytokines, and develop numerous human mast cells. For desensitization, we used anti-huFcεRIα mAbs that bind FcεRIα regardless of its association with IgE (noncompeting mAbs), and/or mAbs that compete with IgE for huFcεRIα binding (competing mAbs). Anaphylaxis was induced by intravenous injection of antigen or anti-huIgE mAb. Anti-huFcεRIα mAb rapid desensitization was safer and more effective than allergen rapid desensitization and suppressed anaphylaxis more rapidly than omalizumab or ligelizumab. Rapid desensitization of naïve, IgE-sensitized huFcεRIα mice and huFcεRIα/F709 mice that were egg-allergic with anti-FcεRIα mAbs safely removed >98% of IgE from peritoneal mast cells and completely suppressed IgE-mediated anaphylaxis. Rapid desensitization of reNSGS mice with anti-FcεRIα mAbs also safely removed ∼98% of mast cell IgE and prevented IgE-mediated anaphylaxis. Rapid desensitization with anti-FcεRIα mAbs may be a safe, effective, and practical way to prevent IgE-mediated anaphylaxis.

Novel role of proton-secreting epithelial cells in sperm maturation and mucosal immunity.

Epithelial cells are immune sensors and mediators that constitute the first line of defense against infections. Using the epididymis, a model for studying tubular organs, we uncovered a novel and unexpected role for professional proton-secreting 'clear cells' in sperm maturation and immune defense. The epididymal epithelium participates in the maturation of spermatozoa via the establishment of an acidic milieu and transfer of proteins to sperm cells, a poorly characterized process. We show that proton-secreting clear cells express mRNA transcripts and proteins that are acquired by maturing sperm, and that they establish close interactions with luminal spermatozoa via newly described 'nanotubes'. Mechanistic studies show that injection of bacterial antigens in vivo induces chemokine expression in clear cells, followed by macrophage recruitment into the organ. Injection of an inflammatory intermediate mediator (IFN-γ) increased Cxcl10 expression in clear cells, revealing their participation as sensors and mediators of inflammation. The functional diversity adopted by clear cells might represent a generalized phenomenon by which similar epithelial cells decode signals, communicate with neighbors and mediate mucosal immunity, depending on their precise location within an organ.

A comparative study of intralesional injection of Candida albicans antigen, bleomycin and 5-fluorouracil for treatment of plane warts

Background Several therapeutic modalities for the treatment of verruca plana (VP) are available, but none has achieved complete cure in all cases with associated risk of side effects. Objective To evaluate efficacy and safety of intralesional injection of Candida albicans (C. albican) antigen, bleomycin and 5-fluorouracil (5-FU) in treatment of VP. Methods Sixty patients with VP were randomly divided into three equal groups who were treated using C. albicans antigen, bleomycin or 5- FU injections every 2 weeks till complete clearance of the lesions or for a maximum of four sessions and followed up for additional 8 weeks. Results A statistically significant higher incidence of complete response was achieved with bleomycin (85%) than C. albicans antigen (60%) which was higher than 5-FU (45%) with a significantly less number of required sessions to achieve best results with bleomycin and candida antigen than 5-FU. Conclusions Candida albicans antigen, bleomycin and 5-FU are helpful modalities for treatment of VP. Bleomycin was the most effective, followed by C. albicans antigen then 5-FU (least effective). Single injection site, clearance of distant warts and decreased incidence of new lesion development – in situ or elsewhere – are additional merits of C. albicans immunotherapy. These modalities are cheap with only transient adverse effects.

Comparative Study between Intralesional Injection of Vitamin D3 and Candida Albicans Antigen in Treatment of Plantar Warts

Background: Numerous therapeutic modalities have been used either singly or in combination to treat recalcitrant warts. However, a single treatment that is entirely effective in all patients is not yet explored. This might be attributed to the absence of specific antiviral medications against human papilloma virus (HPV) infection. Objective: The aim of this work was to compare efficacy of intralesional vitamin D3 in treatment of plantar warts in comparison to candida albicans antigen. Patients and methods: This study included a total of 40 patients suffering from plantar warts, attending at Dermatology and Andrology Outpatient Clinic, Dermatology Department, Al-Azhar University Hospitals. The included subjects were randomly divided into two groups; Group A (Candida antigen group) consisted of 20 patients, subjected to intralesional injection of candida albicans antigen and Group B: (Vitamin D3 group) consisted of 20 patients, subjected to intralesional injection of Vitamin D3. Results: Results revealed that there were no statistically significant correlations between age, sex of patients, duration of treated warts and clinical response in both treatment groups. However, a statistically significant correlation existed between the number of treated warts and response in Vitamin D group. Complete response occurred in patients with low number of warts. At the end, our results showed that there was no statistically significant correlation in complete response between candida antigen and vitaminD3. Both treatments show comparable efficacy and safety in treatment of plantar warts. Conclusion: Treatment of multiple warts by intralesional injection of candida antigen or vitamin D3 is safe and effective, with good cure rates, excellent safety profile and minimal recurrences.

Comparative Study between Intralesional Injection of Vitamin D3 and Candida Albicans Antigen in Treatment of Plantar Warts

Background: Numerous therapeutic modalities have been used either singly or in combination to treat recalcitrant warts. However, a single treatment that is entirely effective in all patients is not yet explored. This might be attributed to the absence of specific antiviral medications against human papilloma virus (HPV) infection. Objective: The aim of this work was to compare efficacy of intralesional vitamin D3 in treatment of plantar warts in comparison to candida albicans antigen. Patients and methods: This study included a total of 40 patients suffering from plantar warts, attending at Dermatology and Andrology Outpatient Clinic, Dermatology Department, Al-Azhar University Hospitals. The included subjects were randomly divided into two groups; Group A (Candida antigen group) consisted of 20 patients, subjected to intralesional injection of candida albicans antigen and Group B: (Vitamin D3 group) consisted of 20 patients, subjected to intralesional injection of Vitamin D3. Results: Results revealed that there were no statistically significant correlations between age, sex of patients, duration of treated warts and clinical response in both treatment groups. However, a statistically significant correlation existed between the number of treated warts and response in Vitamin D group. Complete response occurred in patients with low number of warts. At the end, our results showed that there was no statistically significant correlation in complete response between candida antigen and vitaminD3. Both treatments show comparable efficacy and safety in treatment of plantar warts. Conclusion: Treatment of multiple warts by intralesional injection of candida antigen or vitamin D3 is safe and effective, with good cure rates, excellent safety profile and minimal recurrences.

Tonic contraction develops in the colon during anaphylactic hypotension in anesthetized rats.

Diarrhea is a gastrointestinal symptom associated with systemic anaphylaxis and could be induced by increased colonic motility. We determined colonic motility and expulsion by measuring the intracolonic pressure (ICP) and expelled fluid weight in anesthetized rats during anaphylactic hypotension. Substantial systemic hypotension occurred in every sensitized rat after antigen injection. One min after antigen injection, ICP began to increase and remained elevated for 5min, which was revealed to represent tonic contraction by the video-recording procedure, and was accompanied by increased colonic fluid expulsion. Parasympathectomy composed of subdiaphragmatic vagotomy combined with pelvic nerve transection reduced the duration of the tonic contraction, but not expelled colonic fluid. Furthermore, denervation of afferent parasympathetic nerves produced essentially the same effect as parasympathectomy. Sympathectomy did not significantly change any parameters. In conclusion, the colonic motility during anaphylactic hypotension is characterized by 5-min lasting tonic contraction which is associated with increased colonic fluid expulsion and is involved by parasympathetic nerves, especially their afferents, but not sympathetic nerves, in anesthetized rats.