Lifestyle Changes and Industrialization in the Development of Allergic Diseases.

PURPOSE OF REVIEW: Modernization and Westernization in industrialized and developing nations is associated with a substantial increase in chronic noncommunicable diseases. This transformation has far-reaching effects on lifestyles, impacting areas such as economics, politics, social life, and culture, all of which, in turn, have diverse influences on public health. Loss of contact with nature, alternations in the microbiota, processed food consumption, exposure to environmental pollutants including chemicals, increased stress and decreased physical activity jointly result in increases in the frequency of inflammatory disorders including allergies and many autoimmune and neuropsychiatric diseases. This review aims to investigate the relationship between Western lifestyle and inflammatory disorders. RECENT FINDINGS: Several hypotheses have been put forth trying to explain the observed increases in these diseases, such as 'Hygiene Hypothesis', 'Old Friends', and 'Biodiversity and Dysbiosis'. The recently introduced 'Epithelial Barrier Theory' incorporates these former hypotheses and suggests that toxic substances in cleaning agents, laundry and dishwasher detergents, shampoos, toothpastes, as well as microplastic, packaged food and air pollution damage the epithelium of our skin, lungs and gastrointestinal system. Epithelial barrier disruption leads to decreased biodiversity of the microbiome and the development of opportunistic pathogen colonization, which upon interaction with the immune system, initiates local and systemic inflammation. Gaining a deeper comprehension of the interplay between the environment, microbiome and the immune system provides the data to assist with legally regulating the usage of toxic substances, to enable nontoxic alternatives and to mitigate these environmental challenges essential for fostering a harmonious and healthy global environment.

The effects of enoxaparin treatment in a xenograft mouse model of oral squamous cell carcinoma: A pilot study.

BACKGROUND: Recent studies suggest that enoxaparin may have therapeutic effects on oral squamous cell carcinoma. We aimed to assess this effect utilizing xenograft mouse model through evaluations of proliferation and angiogenesis markers at the RNA and protein levels. METHODS: Mice were divided into enoxaparin treatment (n = 4), positive control (n = 4) and negative control (n = 3) groups. Immunohistochemical analyses were performed utilizing Bcl-2, Bax and Ki-67 antibodies. Expression levels of proliferation and apoptosis related genes were calculated utilizing qRT-PCR. Time-dependent proliferation assays were performed in OSC-19 and HEK293 cell-lines. RESULTS: Bax antibody showed positive staining in the cytoplasm and nuclei of tumor cells, while Bcl-2 antibody displayed staining only in the cytoplasm. A proliferation index of 15%-20% was found in all groups with the Ki-67 marker indicating no metastasis. Enoxaparin treatment caused decrease in BCL2, BAX and CCNB1 genes' expressions. Compared to HEK293, proliferation assays demonstrated higher division rates in OSC-19 with a significant decrease in viability after 96 h. CONCLUSION: Reduced BCL-2 expression indicates a regression of tumor growth, but reduced BAX expression is not correlated with increased apoptosis. Despite the aggressive nature of OSC-19, our results showed a low cell viability with a high division rate when compared with the control HEK293. This paralleled our in vivo findings that showed absence of lymph node metastasis across all mice groups. This discrepancy with the literature suggests that further investigations of the underlying mechanisms and protein-level analyses are needed to draw definitive conclusions about the effect of enoxaparin on OSC-19 behavior.

How does global warming contribute to disorders originating from an impaired epithelial barrier?

The epithelial barrier represents the point of contact between the host and the external environment. It is the first line of defense against external insults in the skin and in the gastrointestinal and upper and lower respiratory tracts. The steep increase in chronic disorders in recent decades, including allergies and autoimmune disorders, has prompted studies to investigate the immune mechanisms of their underlying pathogeneses, all of which point to a thought-provoking shared finding: disrupted epithelial barriers. Climate change with global warming has increased the frequency of unpredictable extreme weather events, such as wildfires, droughts, floods, and aberrant and longer pollination seasons, among many others. These increasingly frequent natural disasters can synergistically damage the epithelial barrier integrity in the presence of environmental pollution. A disrupted epithelial barrier induces proinflammatory activation of epithelial cells and alarmin production, namely, epithelitis. The "opened" epithelial barrier facilitates the entry of the external exposome into and underneath the epithelium, triggering an expulsion response driven by inflammatory cells in the area and chronic inflammation. These changes are associated with microbial dysbiosis with colonizing opportunistic pathogens and decreased commensals. These cellular and molecular events are key mechanisms in the pathogenesis of numerous chronic inflammatory disorders. This review summarizes the impact of global warming on epithelial barrier functions in the context of allergic diseases. Further studies in the impact of climate change on the dysfunction of the epithelial barriers are warranted to improve our understanding of epithelial barrier-related diseases and raise awareness of the environmental insults that pose a threat to our health.

The epithelial barrier theory: Development and exacerbation of allergic and other chronic inflammatory diseases.

It is now longer than half a century, humans, animals, and nature of the world are under the influence of exposure to many newly introduced noxious substances. These exposures are nowadays pushing the borders to be considered as the causative or exacerbating factors for many chronic disorders including allergic, autoimmune/inflammatory, and metabolic diseases. The epithelial linings serve as the outermost body's primary physical, chemical, and immunological barriers against external stimuli. The "epithelial barrier theory" hypothesizes that these diseases are aggravated by an ongoing periepithelial inflammation triggered by exposure to a wide range of epithelial barrier-damaging insults that lead to "epithelitis" and the release of alarmins. A leaky epithelial barrier enables the microbiome's translocation from the periphery to interepithelial and even deeper subepithelial areas together with allergens, toxins, and pollutants. Thereafter, microbial dysbiosis, characterized by colonization of opportunistic pathogen bacteria and loss of the number and biodiversity of commensal bacteria take place. Local inflammation, impaired tissue regeneration, and remodeling characterize the disease. The infiltration of inflammatory cells to affected tissues shows an effort to expulse the tissue invading bacteria, allergens, toxins, and pollutants away from the deep tissues to the surface, representing the "expulsion response." Cells that migrate to other organs from the inflammatory foci may play roles in the exacerbation of various inflammatory diseases in distant organs. The purpose of this review is to highlight and appraise recent opinions and findings on epithelial physiology and its role in the pathogenesis of chronic diseases in view of the epithelial barrier theory.

Comparison of mitogen-induced proliferation in child and adult healthy groups by flow cytometry revealed similarities.

The proliferation of antigen-specific lymphocyte clones, the initial step in acquired immunity, is vital for effector functions. Proliferation tests both in immunology research and diagnosis are gaining attendance gradually, while the use of adult healthy individuals as controls of pediatric patients is a question. This study aimed to investigate and compare mitogen-stimulated proliferation responses of total lymphocytes and T- and B-lymphocyte subsets in adult and children healthy donors. Nineteen children and 20 adult healthy donors were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) purified from peripheral blood samples of the donors, by Ficoll gradient centrifugation, were stained with CFSE and were cultured in a 37 â„ƒ CO2 incubator for 120 h with the absence or existence of polyclonal activators: PHA and CD-Mix. After cell culture, PBMCs were stained with monoclonal antibodies against CD4 and CD19, and proliferation percentages of CD4+ T and CD19+ B cells, together with total lymphocytes were determined by flow cytometry. This study revealed similarities between children and adult age groups, concerning mitogenic stimulation of the lymphocytes. The only difference was a significantly high proliferation of pediatric CD4+ T cells in response to PHA. CD4+ T cell responses against PHA were inversely correlated with altering age. When pediatric individuals were distributed into age groups of 0-2 years, 3-5 years, and 6-18 years, PHA responses of CD4+ cells were found to be diminished with advancing age. These findings propose the possibility of enrollment of adult healthy individuals as controls for pediatric patients.

The modulatory action of C-Vx substance on the immune system in COVID-19.

The modulatory effect of C-Vx, a novel therapeutic agent, on the immune system of COVID-19 patients was investigated. The functions of T and NK cells of COVID-19 patients with different disease severity were evaluated by flow cytometry in response to C-Vx stimulation. The levels of pro- and anti-inflammatory cytokines were detected by multiplex assay in supernatants after cell culture with C-Vx. Bradykinin, IRF3, and IFN-α levels were also measured by ELISA in the presence or absence of C-Vx stimulation. As a result, increased CD107a expression was observed on NK cells in response to C-Vx addition. The proliferation of T cell subsets was increased by C-Vx, decreasing by disease severity. IL-4 and IL-10 levels were elevated while IFN-γ and IL-17 levels were reduced in T cells following C-Vx stimulation. However, the levels of pro-inflammatory IL-1ß, IL-6, IL-8, IFN-γ and GM-CSF were significantly increased upon C-Vx stimulation. IFN-α levels tended to increase after incubation with C-Vx. These findings support an immunomodulatory action of C-Vx on the immune system of patients with a mild and moderate phase of COVID-19.

Immune modulation as a consequence of SARS-CoV-2 infection.

Erroneous immune responses in COVID-19 could have detrimental effects, which makes investigation of immune network underlying COVID-19 pathogenesis a requisite. This study aimed to investigate COVID-19 related alterations within the frame of innate and adaptive immunity. Thirty-four patients clinically diagnosed with mild, moderate and severe COVID-19 disease were enrolled in this study. Decreased ILC1 and increased ILC2 subsets were detected in mild and moderate patients compared to healthy controls. NK cell subsets and cytotoxic capacity of NK cells were decreased in severe patients. Moreover, CD3+ T cells were reduced in severe patients and a negative correlation was found between CD3+ T cells and D-dimer levels. Likewise, moderate and severe patients showed diminished CD3+CD8+ T cells. Unlike T and NK cells, plasmablast and plasma cells were elevated in patients and IgG and IgA levels were particularly increased in severe patients. Severe patients also showed elevated serum levels of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-8, reduced intracellular IFN-γ and increased intracellular IL-10 levels. Our findings emphasize that SARS-CoV-2 infection significantly alters immune responses and innate and acquired immunity are differentially modulated in line with the clinical severity of the disease. Elevation of IL-10 levels in NK cells and reduction of CD3+ and CD8+ T cells in severe patients might be considered as a protective response against the harmful effect of cytokine storm seen in COVID-19.

Effect of different cytokines in combination with IL-15 on the expression of activating receptors in NK cells of patients with Behçet's disease.

Behçet's disease (BD) is a systemic, autoinflammatory, chronic disorder which affects various parts of the body in genetically susceptible individuals. BD has a multi-factorial etiopathogenesis which encompasses both innate and adaptive arms of immunity. NK cells, which kill virus-infected or malign cells and provide interaction between adaptive and innate immune system, are also known to involve in the pathogenesis of autoimmune/autoinflammatory diseases including BD. NK cells function in immune responses via the signals obtained from surface-expressed activating and inhibitory receptors. In this study, we aimed to explore NK cell activation status by measuring the levels of activation marker CD69 and activating receptors NKG2D, NKp30, and NKp46 as well as proliferative and cytotoxic capacities in response to stimulation with interleukin (IL)-15-combined cytokines in BD patients. CD4+ and CD8+ T cell responses were also evaluated to compare with those of NK cells. As a result, the expression of activating receptors on NK cells was demonstrated to be varied among patients with active and inactive BD and healthy controls. The proliferation levels of NK cells were elevated in BD patients, especially in inactive phase of disease compared to healthy controls. Additionally, CD107a levels of inactive BD patients were detected to be lower in comparison with healthy controls and active BD patients. These findings suggest that BD patients in active and inactive phases display different activation status of NK cells which indicate NK cells might be associated with immune attacks and remissions during the course of BD.

Combined evaluation of proliferation and apoptosis to calculate IC50 of VPA-induced PANC-1 cells and assessing its effect on the Wnt signaling pathway.

Pancreatic ductal adenocarcinoma (PDAC) is among the most deadly cancers. Since most patients develop resistance to conventional treatments, new approaches are in urgency. Valproic acid (VPA) was shown to induce apoptosis and reduce proliferation in PANC-1 cells. Wnt signaling pathway is known to be involved in apoptosis and PDAC onset. However, VPA-induced apoptosis and its impact on Wnt signaling in PDACs are not linked, yet. We aimed to calculate IC50 of VPA-induced PANC-1 cells by combined analyses of proliferation and apoptosis, while assessing its effect on Wnt signaling pathway. PANC-1 was induced with increased VPA doses and time points. Three independent proliferation and apoptosis assays were performed utilizing carboxyfluorescein succinimidyl ester and Annexin V/PI staining, respectively. Flow cytometry measurements were analyzed by CellQuest and NovoExpress. Taqman hydrolysis probes and SYBR Green PCR Mastermix were assessed in expression analyses of Wnt components utilizing 2-ΔΔCt method. Cell proliferation was inhibited by 50% at 2.5 mM VPA that evoked a significant apoptotic response. Among the screened Wnt components and target genes, only LEF1 exhibited significant four-fold upregulation at this concentration. In conclusion, cancer studies mostly utilize MTT or BrdU assays in estimating cell proliferation and calculating IC50 of drugs, which provided conflicting VPA dosages utilizing PANC-1 cells. Our novel combined approach enabled specific, accurate and reproducible IC50 calculation at single cell basis with no apparent effect on Wnt signaling components. Future studies are needed to clarify the role of LEF1 in this model.

The Role of Natural Killer Cells in Autoimmune Diseases.

Natural killer (NK) cells, the large granular lymphocytes differentiated from the common lymphoid progenitors, were discovered in early 1970's. They are members of innate immunity and were initially defined by their strong cytotoxicity against virus-infected cells and by their important effector functions in anti-tumoral immune responses. Nowadays, NK cells are classified among the recently discovered innate lymphoid cell subsets and have capacity to influence both innate and adaptive immune responses. Therefore, they can be considered as innate immune cells that stands between the innate and adaptive arms of immunity. NK cells don't express T or B cell receptors and are recognized by absence of CD3. There are two major subgroups of NK cells according to their differential expression of CD16 and CD56. While CD16+CD56dim subset is best-known by their cytotoxic functions, CD16-CD56bright NK cell subset produces a bunch of cytokines comparable to CD4+ T helper cell subsets. Another subset of NK cells with production of interleukin (IL)-10 was named as NK regulatory cells, which has suppressive properties and could take part in immune-regulatory responses. Activation of NK cells is determined by a delicate balance of cell-surface receptors that have either activating or inhibitory properties. On the other hand, a variety of cytokines including IL-2, IL-12, IL-15, and IL-18 influence NK cell activity. NK-derived cytokines and their cytotoxic functions through induction of apoptosis take part in regulation of the immune responses and could contribute to the pathogenesis of many immune mediated diseases including ankylosing spondylitis, Behçet's disease, multiple sclerosis, rheumatoid arthritis, psoriasis, systemic lupus erythematosus and type-1 diabetes. Dysregulation of NK cells in autoimmune disorders may occur through multiple mechanisms. Thanks to the rapid developments in biotechnology, progressive research in immunology enables better characterization of cells and their delicate roles in the complex network of immunity. As NK cells stand in between innate and adaptive arms of immunity and "bridge" them, their contribution in inflammation and immune regulation deserves intense investigations. Better understanding of NK-cell biology and their contribution in both exacerbation and regulation of inflammatory disorders is a requisite for possible utilization of these multi-faceted cells in novel therapeutic interventions.

Pseudomonas aeruginosa colonization in cystic fibrosis: Impact on neutrophil functions and cytokine secretion capacity.

BACKGROUND: Chronic colonization with Pseudomonas (P.) aeruginosa worsens the prognosis of cystic fibrosis (CF) patients. This study aims to analyze the functional properties of neutrophils in CF patients with P. aeruginosa colonization. METHODS: Patients with CF (n = 16) were grouped by positivity of P. aeruginosa in sputum culture, as positive (P.+) or negative (P.-), then compared with age and sex matched healthy controls (n = 8). Adhesion molecules, apoptotic index, intracellular CAP-18, interleukin 8 (IL-8), and tumor necrosis factor α (TNF-α) levels of neutrophils, following P. aeruginosa and lipopolysaccharides (LPS) stimulation, were analyzed by flow cytometry. IL-1ß, IL-6, TNF-α, and IL-17 plasma levels were determined by Luminex. RESULTS: Patients with CF had increased phagocytosis of Escherichia coli and P. aeruginosa, upregulated oxidative burst and chemotaxis. Increased neutrophil apoptosis was noted in CF patients. In unstimulated conditions, higher levels of CD16+ TNF-α+ and CD16+ IL-8+ neutrophils were determined, whereas bacteria and LPS stimulation significantly decreased secretion of CAP-18 from CD16+ neutrophils of CF patients. Plasma levels of IL-1ß, TNF-α and IL-17 in P.+ patients were higher than in P.- group. CONCLUSION: Our findings confirm inadequate neutrophil defense towards pathogens in CF. A significant difference in migration, phagocytosis, oxidative burst, percentage of IL-8 producing neutrophils, IL-1ß, TNF-α, and IL-17 secretions were noted among CF patients according to their colonization status, which might induce a further destructive effect on airways, resulting in an unfavorable prognosis for children with CF who also have colonization.

Influence of Innate Immunity on Immune Tolerance.

This review mainly focuses on the mechanisms of peripheral immune tolerance within the perspectives of innate immunity. Healthy immune response requires balanced interaction of the highly specialized elements of immunity within a harmony. Innate immunity supported by microbial pattern recognition receptors, physical anatomical barriers and soluble effectors stands as the first line of defense against non-self-antigens. Innate receptors recognize major classes of pathogens and trigger immediate immune/inflammatory responses. The decisive action has been the key issue in skewing of immune reactivity to a pathogen or to tolerate self- and non-self-antigens. Non-responsiveness to self- or to harmless foreign antigens with means of multiple mechanisms is known as immune tolerance; a non-inflammatory, non-proliferative and suppressive response linked to suppressor molecules as CTLA-4 and cytokines like IL-10, TGF-ß and IL-35, and also to non-inflammatory blocking antibody isotypes as IgG4. Regulatory cells ascertain both induction and maintenance of peripheral tolerance. Allergic diseases, autoimmunity and transplant rejection are the best illustrations of immune tolerance loss. Adaptive immunity responsible for both establishment and maintenance of a long-lasting immune responsiveness is mainly fine-tuned by actions of innate immunity. Better understanding of the relationship between innate immunity and immune tolerance is a prerequisite both for better understanding of pathogenesis of tolerance-related diseases and also for development of novel therapeutic options. CONCLUSION: Recent evidences point the important roles of innate immunity for establishment of immune tolerance with decisive role in central mechanisms. In a peremptory way, a 'balanced tolerance' is essential for the survival.

Mechanisms of allergen-specific immunotherapy and allergen tolerance.

Allergen-specific immunotherapy (AIT) is the mainstay treatment for the cure of allergic disorders, with depicted efficacy and safety by several trials and meta-analysis. AIT impressively contributes to the management of allergic rhinitis, asthma and venom allergies. Food allergy is a new arena for AIT with promising results, especially via novel administration routes. Cell subsets with regulatory capacities are induced during AIT. IL-10 and transforming growth factor (TGF)-ß are the main suppressor cytokines, in addition to surface molecules such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1) within the micro milieu. Modified T- and B-cell responses and antibody isotypes, increased activity thresholds for eosinophils, basophils and mast cells and consequent limitation of inflammatory cascades altogether induce and maintain a state of sustained allergen-specific unresponsiveness. Established tolerance is reflected into the clinical perspectives as improvement of allergy symptoms together with reduced medication requirements and evolved disease severity. Long treatment durations, costs, reduced patient compliance and risk of severe, even life-threatening adverse reactions during treatment stand as major limiting factors for AIT. By development of purified non-allergenic, highly-immunogenic modified allergen extracts, and combinational usage of them with novel adjuvant molecules via new routes may shorten treatment durations and possibly reduce these drawbacks. AIT is the best model for custom-tailored therapy of allergic disorders. Better characterization of disease endotypes, definition of specific biomarkers for diagnosis and therapy follow-up, as well as precision medicine approaches may further contribute to success of AIT in management of allergic disorders.

EAACI Allergen Immunotherapy User's Guide.

Allergen immunotherapy is a cornerstone in the treatment of allergic children. The clinical efficiency relies on a well-defined immunologic mechanism promoting regulatory T cells and downplaying the immune response induced by allergens. Clinical indications have been well documented for respiratory allergy in the presence of rhinitis and/or allergic asthma, to pollens and dust mites. Patients who have had an anaphylactic reaction to hymenoptera venom are also good candidates for allergen immunotherapy. Administration of allergen is currently mostly either by subcutaneous injections or by sublingual administration. Both methods have been extensively studied and have pros and cons. Specifically in children, the choice of the method of administration according to the patient's profile is important. Although allergen immunotherapy is widely used, there is a need for improvement. More particularly, biomarkers for prediction of the success of the treatments are needed. The strength and efficiency of the immune response may also be boosted by the use of better adjuvants. Finally, novel formulations might be more efficient and might improve the patient's adherence to the treatment. This user's guide reviews current knowledge and aims to provide clinical guidance to healthcare professionals taking care of children undergoing allergen immunotherapy.

CD3-CD56+ NK cells display an inflammatory profile in RR-MS patients.

Multiple Sclerosis (MS) is an immune-mediated and neurodegenerative disease of central nervous system. Relapsing-remitting (RR)-MS occurring with acute attacks and remissions, is the most common clinical type of MS. There are different strategies applied in first-line treatment of RR-MS patients such as interferon-beta (IFN-ß) and glatiramer acetate. In this study, activating and inhibitory receptor expressions and interleukin (IL)-22 levels of NK cells were investigated in RR-MS patients with or without IFN-ß therapy. Activating receptor expression and IL-22 levels of NK cells were increased in RR-MS patients under IFN-ß therapy. Elevated NK cells with activating profile and increased IL-22 under IFN-ß therapy suggest that IFN-ß treatment might direct NK cells toward a pro-inflammatory status.

Clinical and immunophenotypic characteristics of patients with chromosome 22q11.2 deletion syndrome: a single institution's experience.

AIM: The aim of this study was to identify the clinical and immunologic features of patients with 22q11.2 deletion syndrome who were followed up in our clinic. Thus, it is aimed to identify the syndrome early, choose the right treatment options according to humoral and cellular immunologic analysis, and enlighten how to follow up these kinds of patients with immunodeficiencies. MATERIAL AND METHODS: We retrospectively collected data by reviewing the files of 11 patients with 22q11.2 deletion syndrome who were followed up in our clinic between January 2003 and January 2015. The diagnoses were based on the patients' clinical, genetic, and immunologic features. Demographic features, family history, initial symptoms on admission, physical findings, and results of immunologic studies of the patients. Age of diagnosis, treatment options, and clinical follow-up were evaluated. RESULTS: The patients' diagnosis age ranged from 1-11 months and the most common symptoms of admission were cardiac murmur and atypical facial appearance, which were detected during a routine physical examination. All patients had cardiac anomalies, and four patients had a history of cardiovascular surgery. Eight patients (72.7%) had a history of severe infection; recurrent lower respiratory tract infections were reported in six patients (54.5%), pulmonary tuberculosis in one patient (9.1%), and moniliasis resistant to treatment was detected in one patient. None of the patients required intravenous immunoglobulin replacement therapy, and antibiotic prophylaxis was administered to two patients with lymphopenia. CONCLUSION: 22q11.2 deletion syndrome is a multi-systemic disorder that should be evaluated by a multidisciplinary team. It should be kept in mind for patients with neonatal hypocalcemic tetany or recurrent infections or atypical facial appearance with cardiac anomalies. Early diagnosis should lead to immunologic analysis and enable the choice of treatment. Preventive measures against infection is recommended for the patients with incomplete immunodeficiency, and thymus transplantation is recommended for patients with complete immunodeficiency.

AMAÇ: Bu çalismada klinigimizde 22q11.2 delesyon sendromu tanisi ile izlenmekte olan hastalarin klinik ve immünolojik niteliklerinin tanimlanmasi amaçlanmistir. Böylece hastaligin erken taninmasina yardimci olmak, humoral ve hücresel immünolojik verilere göre tedavi seçeneklerine yönlendirmek ve bu immün yetersizlik hastalarinin nasil izlenecegine isik tutmak hedeflenmistir. GEREÇ VE YÖNTEMLER: Klinigimizde, Ocak 2003-Ocak 2015 tarihleri arasinda 22q11.2 delesyon sendromu tanisi ile izlenmekte olan 11 olgunun dosya verileri geriye dönük olarak incelendi. Hastalarin tanisi; klinik, genetik ve immünolojik niteliklere göre konuldu. Çalismaya alinan tüm hastalarin demografik nitelikleri, aile öyküsü, basvuru yakinmalari, fizik baki bulgulari, immünolojik inceleme sonuçlari, tani yasi, tedavi seçenegi ile klinik izlemleri irdelendi. BULGULAR: Hastalarin tani yasi 1-11 ay arasinda degismekte olup, en sik basvuru yakinmasi fizik baki sirasinda farkedilen atipik yüz görünümü ve kalpte duyulan üfürüm idi. Tüm hastalarin kalbinde anomali bulunur iken, dört hastada kardiyovasküler cerrahi girisim öyküsü vardi. Sekiz hastada (%72,7) ciddi enfeksiyon geçirme öyküsü olup; alti hastada (%54,5) sik tekrarlayan alt solunum yolu enfeksiyonu, bir hastada (%9,1) akciger tüberkülozu ve bir hastada (%9,1) inatçi moniliazis saptandi. Lenfopenik olan iki hastaya (%18,2) antibiyotik profilaksisi uygulanirken, hiçbir hastada intravenöz immünglobulin replasman tedavisi gereksinimi olmadi. ÇIKARIMLAR: Kromozom 22q11.2 delesyon sendromu, çoklu organ tutulumu nedeniyle birçok uzmanlik daliyla birlikte izlenmelidir. Yenidogan döneminde hipokalsemik tetani geçiren, kalp anomalisine eslik eden atipik yüz görünümü olan ve yineleyen enfeksiyon öyküsü olan hastalarda mutlaka akla getirilmelidir. Erken tani ile hastalarin immün sistem incelemesinin yapilmasi; kismi eksiklik durumunda enfeksiyonlardan koruyucu önlemler alinmasini, tam hücresel immün bozukluk olmasi durumunda ise timus nakli yapilmasina olanak saglayacaktir.

Chronic rhinosinusitis: pathogenesis, therapy options, and more.

INTRODUCTION: When rhinosinusitis - the inflammation of the nasal cavity and paranasal sinuses - persists for over 12 weeks, it is termed 'chronic rhinosinusitis' (CRS). Both innate and adaptive immunity contribute to the heterogeneous inflammatory pathogenesis of CRS, which is driven by genetic and environmental factors and the microbiome. CRS is classified by the presence of polyps. Molecular mechanisms in CRS with nasal polyps are similar to those in atopic diseases. AREAS COVERED: This review focuses on the immune pathogenesis of CRS, differences between the two CRS subtypes, and latest treatments that may aid in the provision of personalized medicine. EXPERT OPINION: Basic research in the last decade has helped significantly in enhancing our knowledge of the pathophysiologic processes of CRS, due to which there is now a better understanding of the associated natural history, physiopathology, novel treatments, and prevention strategies. Treatment success depends on the clarification of the underlying pathogenesis and disease-contributing factors. The exploration of disease endotypes and introduction of novel agents are important advancements. Prior studies performed without disease-endotyping resulted in the inefficiency of certain drugs and insignificant results. The identification of biomarkers, development of personalized approaches, and utilization of disease algorithms are required for CRS therapy success.

Precision/Personalized Medicine in Allergic Diseases and Asthma.

Like many other chronic diseases, every allergic patient has different characteristics based on clinical course, treatment responsiveness and disease outcomes, which are associated with the genetic and epigenetic control of molecular mechanisms and environment. This variability necessitates the establishment of patient-tailored and precision approaches in handling allergic disorders. Better understanding of the underlying pathophysiological mechanisms for the development of allergic disorders will provide more rationale strategies based on individual cases in controlling and treating these disorders. Endotyping, phenotyping, genotyping and theratyping, and biomarkers are keywords in this area and have been gaining lots of attention in the field of precision medicine, which aims to revolutionize patient care and develop better prevention and treatment strategies. In addition, precision health is a new concept that brings precise approaches to the scene for being healthy and prevention of allergic disease and asthma. The specialty of allergy has a leading role in the field, because allergen-specific immunotherapy started 105 years ago, and is historically a leading personalized/precision medicine approach in all medicine disciplines providing the possibility of cure in an individualized manner instead of conventional symptomatic treatments.