The Association of Vitamin D Receptor Gene Polymorphisms with Vitamin D, Total IgE, and Blood Eosinophils in Patients with Atopy.

BACKGROUND: In order to improve the control of atopic diseases, it is important to clarify the pathogenesis of atopy and identify its various triggers. Single nucleotide polymorphisms (SNPs) of the vitamin D receptor gene (VDR) may impact atopy. The aim of this study was to investigate the possible associations between VDR SNPs and vitamin D, total IgE, and eosinophils in atopy. METHODS: In total, 203 adults, including 122 patients with atopic diseases (45 with atopic dermatitis, 77 with allergic asthma) and 81 healthy controls, were involved in the study. The blood eosinophil count was determined with an automated hematology analyzer. Vitamin D and total immunoglobulin E (IgE) levels were evaluated using the ELISA method. Polymorphisms in the VDR gene were analyzed with real-time PCR using TaqMan probes. RESULTS: We analyzed six VDR single nucleotide polymorphisms and found a significant association between VDR rs731236 GG genotype and normal vitamin D levels in atopic patients and healthy subjects (OR 11.33; 95% CI: 1.049-122.388 and OR 4.04; 95% CI: 1.117-14.588, respectively, p < 0.05). Additionally, the study results revealed a significant relationship between the VDR rs2228570 GG genotype and normal vitamin D levels in patients with atopy and healthy subjects (OR 3.80; 95% CI: 1.190-12.134 and OR 2.09; 95% CI: 1.044-4.194, respectively, p < 0.05). The rs2228570 allele A was associated with decreased vitamin D levels in patients with atopy and healthy subjects (OR 0.28; 95% CI: 0.098-0.804 and OR 0.229; 95% CI: 0.069-0.761, respectively, p < 0.05). The VDR rs3847987 genotypes AA and AC were significantly associated with normal vitamin D levels in healthy subjects (OR 35.99; 95% CI: 6.401-202.446 and OR 4.72; 95% CI: 1.489-15.007, respectively, p < 0.05). In addition, a decreased amount of vitamin D was associated with atopic diseases such as atopic dermatitis and allergic asthma (OR 0.49; 95% CI: 0.439-1.308 and OR 0.58; 95% CI: 0.372-0.908, respectively, p < 0.05). The rs11168293 allele T was associated with the normal range of total IgE in atopy (OR 2.366; 95% CI: 1.133-5.027; p < 0.05). Significant associations were found between VDR rs731263 allele G, rs11168293 allele G, and increased blood eosinophil levels in patients with atopy (OR 0.319; 95% CI: 0.163-0.934 and OR 0.323; 95% CI: 0.112-0.935, respectively, p < 0.05). CONCLUSIONS: A decreased vitamin D level showed a significant relationship with atopic diseases (atopic dermatitis and allergic asthma). The association between the VDR gene polymorphisms rs2228570, rs731236, and rs11168293 and vitamin D, total IgE, and blood eosinophils in patients with atopy suggested that VDR polymorphisms and the vitamin D level should be considered when examining the factors associated with atopy.

Genetic Diversity in Bronchial Asthma Susceptibility: Exploring the Role of Vitamin D Receptor Gene Polymorphisms in Varied Geographic Contexts.

Bronchial asthma (BA) exhibits varying prevalence across global populations, prompting a comprehensive investigation into genetic and environmental determinants. Vitamin D is a potent immunomodulator capable of suppressing inflammatory signals in several cell types involved in the asthmatic response; it exerts effects on the immune system by binding to the nuclear vitamin D receptor (VDR). VDR gene genetic variations are affecting serum vitamin D levels with a possible role in the BA risk. The current study aimed to examine the complex interaction of various factors (genetic background, serum vitamin D levels, and geographic location) to identify differences in the influence of these factors on the susceptibility to asthma between populations at different latitudes. Focusing on Eastern European cohorts from Latvia and Lithuania and comparing them with published data on East Asian populations, we explore the impact of VDR gene polymorphisms on BA susceptibility. Genotyping four key VDR SNPs and assessing their association with 25-hydroxyvitamin D levels, our study unveils significant associations of the studied loci with the risk of asthma-both risk-reducing and increasing effects, differently distributed between Baltic and East Asian populations. The functional effects of in silico VDR gene genetic variations are also identified and discussed.

UCRAID (Ukrainian Citizen and refugee electronic support in Respiratory diseases, Allergy, Immunology and Dermatology) action plan.

Eight million Ukrainians have taken refuge in the European Union. Many have asthma and/or allergic rhinitis and/or urticaria, and around 100,000 may have a severe disease. Cultural and language barriers are a major obstacle to appropriate management. Two widely available mHealth apps, MASK-air® (Mobile Airways Sentinel NetworK) for the management of rhinitis and asthma and CRUSE® (Chronic Urticaria Self Evaluation) for patients with chronic spontaneous urticaria, were updated to include Ukrainian versions that make the documented information available to treating physicians in their own language. The Ukrainian patients fill in the questionnaires and daily symptom-medication scores for asthma, rhinitis (MASK-air) or urticaria (CRUSE) in Ukrainian. Then, following the GDPR, patients grant their physician access to the app by scanning a QR code displayed on the physician's computer enabling the physician to read the app contents in his/her own language. This service is available freely. It takes less than a minute to show patient data to the physician in the physician's web browser. UCRAID-developed by ARIA (Allergic Rhinitis and its Impact on Asthma) and UCARE (Urticaria Centers of Reference and Excellence)-is under the auspices of the Ukraine Ministry of Health as well as European (European Academy of Allergy and Clinical immunology, EAACI, European Respiratory Society, ERS, European Society of Dermatologic Research, ESDR) and national societies.

Vitamin D receptor and vitamin D binding protein gene polymorphisms in patients with asthma: a pilot study.

BACKGROUND: The effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and vitamin D binding protein (VDBP). Polymorphisms in VDR or VDBP genes may affect vitamin D levels, influencing the pathogenesis of asthma and atopy. The aim of this study was to investigate the possible association of VDR and VDBP gene single-nucleotide polymorphisms (SNP), 25-hydroxyvitamin D (25(OH)D), blood eosinophils and total IgE level in subjects with asthma in comparison with healthy individuals. METHODS: This case-control study enrolled 63 subjects with asthma (45 allergic and 18 non-allergic) and 32 healthy subjects were involved in the study. Sensitization of subjects to inhaled allergens was determined by a skin prick test, lung function was evaluated by spirometry. Blood eosinophil count was determined by standard methods. Serum 25(OH)D and total IgE levels were evaluated by ELISA. Polymorphisms in the VDR and VDBP genes on the 12q13.11 and 4q13.3 chromosomal region were analyzed using TaqMan SNP Genotyping Assay probes. RESULTS: In asthma patients with vitamin D deficiency (< 20 ng/ml) the allele G of rs11168293 of VDR was more common than in those having insufficiency (20-30 ng/ml) of vitamin D (63% and 31%, p < 0.05). Moreover, asthmatic subject with rs11168293 G allele has significant higher blood eosinophil count compared to asthmatic without the rs11168293 G allele (8.5 ± 12.3% vs. 5.1 ± 1.5%, p < 0.05). Significantly higher IgE level was found in subjects with allergic asthma with the allele A of rs7041 on VDBP gene than in those without this allele (540 ± 110 and 240 ± 80 IU/ml, p < 0.05). CONCLUSIONS: The association of polymorphisms in VDBP and VDR gene, the rs11168293 G allele and the rs7041 A allele, with 25(OH)D, blood eosinophil and total IgE level in asthma, let us suggest that vitamin D, VDR and VDBP gene polymorphisms are important in pathogenesis of asthma despite its form in relation to atopy.

Prevalence of COVID-19 in Kidney Transplant Patients in Relation to Their Immune Status after Repeated Anti-SARS-CoV-2 Vaccination.

The prospective study was conducted to evaluate the prevalence of COVID-19 in kidney transplant patients in relation to their immune status after three doses of the BNT162b2 (Pfizer-BioNTech) vaccine during one post-pandemic year based on the experience of one center-Hospital of Lithuanian University of Health Sciences. Thirty-three patients were invited for a follow-up visit 3 to 6 weeks after anti-SARS-CoV-2 vaccination and were obliged to report having COVID-19 during the one-year post-pandemic period. Forty-two percent of patients developed antibody response against SARS-CoV-2 after the third dose of the vaccine. The number of COVID-19 cases during the post-pandemic period did not differ significantly between seropositive and seronegative patients. However, only seronegative patients were hospitalized due to COVID-19. The anti-SARS-CoV-2 antibody titer in seropositive patients correlated with a relative number of CD3+ cells (R = 0.685, p = 0.029). The CD8+/CD38+ ratio in this group increased 2-fold after the anti-SARS-CoV-2 vaccination. Higher antibody response to the COVID-19 vaccine was associated with better kidney function. The anti-SARS-CoV-2 antibody titer relation with the components of cellular immunity (CD3+ cells and CD8+/CD38+ ratio) shows a role of both chains during the response to the anti-SARS-CoV-2 vaccine in kidney transplant patients.

Clusters based on immune markers in a Lithuanian asthma cohort study.

OBJECTIVE: Asthma is divided into various distinct phenotypes on the basis of clinical characteristics, physiological findings, and triggers, and phenotyping is usually performed in a hypothesis-driven univariate manner. However, phenotyping can also be performed using computer algorithms to evaluate hypotheses-free relationships among many clinical and biological characteristics. We aimed to identify asthma phenotypes based on multiple demographic, clinical, and immunological characteristics. METHODS: Cluster analysis in R v3.5.0 was performed using asthma patient data. A total of 170 adult patients with asthma (diagnosed according to the GINA recommendations) were recruited to the study. All patients completed questionnaires about their smoking history and underwent physical examination, spirometry, skin-prick test, blood sample collection to evaluate peripheral blood cell counts and serum IgE, periostin, and interleukin (IL)-33 levels, as well as body mass index measurements. Data normality was checked with histograms and QQ plots. Hierarchical clustering was performed using Ward's linkage with Ward's clustering criterion. The optimal number of clusters was validated using the Dunn criterion as well as by comparing different clustering algorithms using the clValid package. RESULTS: Three clusters characterizing asthma phenotypes were identified: (1) early-onset, highly atopic, and eosinophilic asthma associated with male sex and high levels of IL-33 and periostin; (2) late-onset, eosinophilic asthma associated with female sex and low levels of IL-33 and periostin; and (3) late-onset, obese, neutrophilic asthma associated with female sex, persistent airway obstruction, and very low IL-33 and periostin levels.

Induction of Bystander and Abscopal Effects after Electroporation-Based Treatments.

Electroporation-based antitumor therapies, including bleomycin electrotransfer, calcium electroporation, and irreversible electroporation, are very effective on directly treated tumors, but have no or low effect on distal nodules. In this study, we aimed to investigate the abscopal effect following calcium electroporation and bleomycin electrotransfer and to find out the effect of the increase of IL-2 serum concentration by muscle transfection. The bystander effect was analyzed in in vitro studies on 4T1tumor cells, while abscopal effect was investigated in an in vivo setting using Balb/c mice bearing 4T1 tumors. ELISA was used to monitor IL-2 serum concentration. We showed that, similarly to cell treatment with bleomycin electrotransfer, the bystander effect occurs also following calcium electroporation and that these effects can be combined. Combination of these treatments also resulted in the enhancement of the abscopal effect in vivo. Since these treatments resulted in an increase of IL-2 serum concentration only in mice bearing one but not two tumors, we increased IL-2 serum concentration by muscle transfection. Although this did not enhance the abscopal effect of combined tumor treatment using calcium electroporation and bleomycin electrotransfer, boosting of IL-2 serum concentration had a significant inhibitory effect on directly treated tumors.

Adverse Events and Immunogenicity of mRNA-Based COVID-19 Vaccine among Healthcare Workers: A Single-Centre Experience.

Background and Objectives: The safety and effectiveness of vaccines are among the key priorities in COVID-19 pandemic management. Moreover, evidence-based data regarding vaccine safety and immunogenicity can play an important role in building the trust of the community regarding vaccination. The aim of this study was to investigate the safety and immunogenicity of Pfizer-BioNTech vaccine among healthcare workers in one hospital, 21 days after first dose. Materials and Methods: This study was conducted in the Hospital of the Lithuanian University of Health Sciences between February and March 2021. Hospital employees who arrived to receive the second dose of the Pfizer-BioNTech vaccine 21 days after the first one were invited to participate in the study: they were asked to complete an anonymous adverse events questionnaire and were offered a SARS-CoV-2 IgG/IgM rapid test. The study was performed at a single point, 21 days after the first dose of the vaccine. Results: Data of 4181 vaccine recipients were analysed. The first vaccine dose was associated with a 53.6% incidence of adverse events, mainly local reactions. Adverse events occurred more frequently in younger participants and women. Moderate adverse events were experienced by 1.4% of the vaccine recipients; 6.2% were incapacitated. Of the 3439 participants who performed a rapid IgG test, 94.5% were positive for IgG antibodies after the first vaccine dose. Seroconversion rates were lower in participants older than 47 years. Conclusions: Despite 1.4% moderate adverse events, no safety concerns or anaphylaxis were identified. The Pfizer-BioNTech vaccine induced an immune response in the overwhelming majority of recipients after a single dose. Younger participants experienced adverse events and were positive for IgG antibodies more frequently than older counterparts. It is important to mention that this study specifically considered short-term safety and reactions following vaccination and that long-term adverse effects were not investigated in the study. Thus, future research into both long-term adverse reactions and immune system programming is essential.

Systemic and local cytokine profile and risk factors for persistent allergic airway inflammation in patients sensitised to house dust mite allergens.

OBJECTIVE: To evaluate cytokine profile, vitamin D status, symptom score and quality of life in patients with persistent allergic airway diseases sensitised to house dust mites (HDM) in comparison with healthy individuals. MATERIAL AND METHODS: Patients sensitized to HDM with persistent AR and having symptoms for at least 2 years with or without AA were involved into the study. Measurements of vitamin D level in serum and IL-10, IL-13, IL-17, IL-22, IL-33 and IFN-gamma in serum and nasal lavage were performed by ELISA. RESULTS: Eighty-one subjects were involved into the study. Serum IL-10 concentration was higher in patients with AR than in patients with AR and AA (6.71 ± 1.73 vs. 1.98 ± 0.24, p < 0.05). IFN-gamma level in nasal lavage was higher in patients with AR and AA than in patients with AR (p < 0.01) and healthy individuals (p < 0.05) (7.50 ± 0.37 vs. 6.80 ± 0.99 vs. 6.50 ± 0.22). Serum IL-22 negatively correlated with IL-22 in nasal lavage, whereas serum IFN-gamma positively correlated with IFN-gamma in nasal lavage. Positive correlation between serum IL-17 and total IgE and negative correlation between IL-17 in nasal lavage and eosinophils in nasal smear were found in patients with AR and AA. Serum IFN-gamma decreased the risk of AR for healthy individuals. Serum IL-10 and vitamin D decreased risk for development of AA for patients with AR. IL-22 in serum and IL-10 and IL-33 in nasal lavage increased this risk. CONCLUSION: Novel cytokines such as IL-22, IL-17 and IL-33 and vitamin D may be involved in pathogenesis of persistent airway inflammation in patients sensitized to HDM.

Immune Response after SARS-CoV-2 Vaccination in Kidney Transplant Patients.

Background and Objectives: The prospective study was conducted to evaluate humoral and cellular immune responses after two doses of BNT162b2 (Pfizer-BioNTech) vaccine and possible relation with other factors (medication, etc.) in kidney transplant patients. Materials and Methods: Out of 167 vaccinated patients, 136 agreed to a follow-up visit three to six weeks after vaccination. Results: Only 39 patients (29%) developed antibody response against SARS-CoV-2 (≥35.2 binding antibody units (BAU)/mL) after full vaccination. Multivariate binary logistic regression analysis showed that predictive factors for good antibody response to the COVID-19 vaccine were better kidney function, higher hemoglobin level, and no use of mycophenolate mofetil for immunosuppression. For seropositive kidney transplant patients there was a significant negative correlation between anti-SARS-CoV-2 antibody titer and CD4/CD8 ratio (Spearman's correlation coefficient -0.4, p = 0.02), percentage of CD19+ cells (r = -0.37, p = 0.02), and a positive correlation with percentage of CD8+ cells (r = 0.4, p = 0.01). There was an increase of total leucocyte count after vaccination in the total studied population, and in the group of responders. Conclusions: Only one third of kidney transplant patients develop sufficient antibody responses after full COVID-19 vaccination with Pfizer-BioNTech. Better kidney function, higher hemoglobin level, and no use of mycophenolate mofetil for immunosuppression increases the adequacy of response. The antibody titers correlated positively with relative number of CD8+ cells and negatively with CD4/CD8 ratio in responders.

DiHS/DRESS syndrome induced by second-line treatment for tuberculosis and Epstein-Barr virus.

Drug-induced hypersensitivity syndrome (DiHS) or drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe adverse drug-induced reaction characterized by various symptoms: skin rash, fever, lymph node enlargement and internal organ involvement, which starts within 2 weeks to 3 months after drug initiation. It is challenging to diagnose this syndrome due to the variety of cutaneous and visceral symptoms. Different mechanisms have been implicated in its development, including genetic susceptibility associated with human leucocyte antigen (HLA) loci, detoxification defects leading to reactive metabolite formation and subsequent immunological reactions, slow acetylation, and reactivation of human herpes, including Epstein-Barr virus and human herpes virus (HHV)-6 and HHV-7. The most frequently reported causes of DiHS/DRESS are antiepileptic agents, allopurinol and sulfonamides. We report a case of DiHS/DRESS induced by second-line treatment for tuberculosis, prothionamide and para-aminosalicylic acid, and Epstein-Barr virus re-infection. Patch testing, which was performed in this case, is not fully standardized, but it can be helpful and a safe way to evaluate and diagnose DiHS/DRESS.

Vitamin D receptor gene polymorphisms in atopy.

BACKGROUND: The occurrence of allergic conditions, for example allergic asthma, rhinitis, and atopic dermatitis, is rising worldwide. These allergic conditions are associated with poor life quality. Vitamin D is proposed to be linked with increased risk and severe forms of allergic diseases. AIMS: This review article aimed to evaluate the vitamin D level role and polymorphisms of vitamin D receptor gene (VDR) in atopy. METHODS & MATERIALS: We analyzed publications that were focusing on levels of vitamin D and/or polymorphism analysis of vitamin D receptor gene in allergic asthma, rhinitis, and atopic dermatitis patients. RESULTS: We noticed that levels of vitamin D are extensively studied in atopy by many research groups, however, polymorphisms of vitamin D receptor gene and their link with levels of vitamin D lack comprehensive data. There is evidence that vitamin D may be associated with anti-inflammatory effects in allergic diseases. Some of VDR polymorphisms also may play a role in pathogenesis of these diseases. However, the data from different studies are controversial. DISCUSSION: The results of different studies are usually inconsistent, most probably due to populational bias or differences in methodology. Even though, more evidence shows a positive impact of vitamin D on the risk and outcomes of allergic diseases, especially atopic dermatitis, and asthma. CONCLUSIONS: There is controversial data about the level of vitamin D and its role in atopy; however, more evidence shows a positive impact on the risk and outcomes of allergic diseases.

Interleukin-32 in Pathogenesis of Atopic Diseases: Proinflammatory or Anti-Inflammatory Role?

Atopic diseases, such as atopic dermatitis (AD), allergic asthma (AA), and allergic rhinitis (AR), are increasingly becoming a worldwide issue. This atopic triad originates at an early age and on a multifactorial basis, causing significant discomfort to susceptible individuals. The global case number is now reaching new highs, so exploring immune system regulation and its components is becoming critical. One cytokine, interleukin-32 (IL-32), is involved in inflammation and regulation of the immune system. It has nine isoforms that show varying degrees of expression, both intracellularly and extracellularly. IL-32 is secreted by immune cells, such as monocytes, macrophages, natural killer cells, and T cells, and by nonimmune cells, including fibroblasts, keratinocytes, and endothelial cells. Its production is regulated and augmented by microorganisms, mitogens, and other cytokines. Early studies demonstrated that IL-32 was an immune regulator that functioned to protect against inflammatory diseases, including AD, AA, and AR, and proposed a proinflammatory role for IL-32 in immune regulation and symptom exacerbation. However, several later reports suggested that IL-32 is downregulated in inflammatory diseases and exerts an anti-inflammatory effect. This review article focuses on recent findings regarding the detrimental and protective roles of IL-32 in development and management of inflammatory diseases. The exact role of IL-32 in AD, AA, and AR still remains to be elucidated. Future research should explore new avenues of IL-32 functionality in human inflammatory diseases.

Translation, adaption and validation of the total nasal symptom score (TNSS) for Lithuanian population.

BACKGROUND: Allergic rhinitis is one of the most prevalent allergic diseases worldwide which diagnosis is based on typical clinical signs and positive results of allergic tests. Selection and evaluation of treatment is based mainly on subjective symptoms. Objective measurement of patients' complaints is necessary for proper documentation and follow-up. There are no short simple validated questionnaire assessing nasal symptoms in patients with allergic rhinitis in Lithuania. Total nasal symptoms score (TNSS) is a brief questionnaire which evaluate the severity of main symptoms of allergic rhinitis widely used in different countries. Our aim was to translate the TNSS in the Lithuanian language and to validate it. METHODS: Prospective cross-cultural adaption and validation study was performed. Linguistic validation of TNSS was performed and validity and reliability were assessed. Patients with chronic allergic and non-allergic rhinitis and healthy individuals were included in this study. Patients had to complete translated version of TNSS. Patients with allergic rhinitis additionally were asked to fill Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). RESULTS: Seventy-six individuals were involved into the study: 16 with non-allergic rhinitis (NAR) (21.1%), 49 with allergic rhinitis (AR) (64.5%) and 11 healthy individuals (14.5%). Cronbach's α was 0.87. TNSS score was significantly higher in patients with NAR and AR compared with healthy individuals (3.56 ± 2.28 vs. 4.28 ± 2.46 vs. 0.27 ± 0.91). Positive significant correlation was found between TNSS score and RQLQ score (rs = 0.77, p < 0.01). CONCLUSIONS: The Lithuanian version of the TNSS proved to be a valid instrument for assessing nasal symptoms in patients with allergic rhinitis.

Role of IL-22 in persistent allergic airway diseases caused by house dust mite: a pilot study.

BACKGROUND: Persistent allergic airway diseases cause a great burden worldwide. Their pathogenesis is not clear enough. There is evidence that one of the recently described cytokine interleukin (IL) 22 may be involved in the pathogenesis of these diseases. Scientists argue if this cytokine acts as proinflammatory or anti-inflammatory agent. The aim of this study was to investigate IL-22 level in patients with persistent allergic airway diseases caused by house dust mite (HDM) in comparison with healthy individuals and to evaluate its relationship with IL-13 and IL-10 level, symptoms score and quality of life. METHODS: Patients with persistent allergic rhinitis caused by HDM and having symptoms for at least 2 years with or without allergic asthma were involved into the study. Measurements of IL-22, IL-13 and IL-10 and in serum and nasal lavage was performed by ELISA. Questionnaires assessing symptoms severity and quality of life were used. RESULTS: A tendency was observed that IL-22 in serum and nasal lavage was higher in patients with allergic airway diseases compared to control group (14.86 pg/ml vs. 7.04 pg/ml and 2.67 pg/ml vs. 1.28 pg/ml, respectively). Positive statistically significant correlation was estimated between serum IL-22 and serum IL-10 (rs = 0.57, p < 0.01) and IL-13 (rs = 0.44, p < 0.05) level. Moreover, positive significant correlation was found between IL-22 in nasal lavage and IL-10 in nasal lavage (rs = 0.37, p < 0.05). There was a negative statistically significant correlation between serum IL-22 and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) (rs = - 0.42, p < 0.05). CONCLUSION: Our study showed a possible anti-inflammatory effect of IL-22 in patients with persistent allergic airway diseases caused by HDM.

Immune system in the pathogenesis of chronic cough.

Chronic cough is a common symptom of various chronic diseases. However, the vast majority of individuals with conditions that are commonly associated with cough, such as asthma and GERD, do not have chronic cough. This implies that cough reflex sensitivities differ among individuals. It is known that in the pathogenesis of cough, the nervous system plays a vital role. Recently more information about the role of the immune system and its interaction with the nervous system in the pathogenesis of cough has appeared in the literature. The aim of this article is to review the most recent data about the role of the immune system in the pathogenesis of chronic cough.

Interleukin-22 in Allergic Airway Diseases: A Systematic Review.

The immune system plays an important role in the pathogenesis of many disorders, including allergic airway diseases. There are studies suggesting that interleukin (IL)-22 can be important in the development of these diseases. However, it is not known if this cytokine acts as proinflammatory or anti-inflammatory agent. This systematic review aimed to analyze level and role of IL-22 in patients with allergic airway diseases in comparison with healthy individuals. Systematic review included only observational studies with patients having allergic rhinitis and/or allergic asthma. The primary outcome measure was IL-22 level in patients with allergic asthma and/or allergic rhinitis. A total of 95 articles were found. Overall, 6 articles were included in systematic review. Five of these studies showed that IL-22 was increased in patients with allergic airway diseases compared with control group. Majority of studies revealed relation between IL-22 level and severity of allergic asthma and allergic rhinitis. Some studies showed positive relation between IL-22 level and total immunoglobulin E (IgE), specific IgE, and eosinophil count in nasal mucosa. IL-22 level is increased in children and adults with allergic airway diseases and is likely to be associated with proinflammatory features.

Elevated levels of interleukin-33 are associated with allergic and eosinophilic asthma.

IL-33 is a recently discovered cytokine which plays an important role in asthma pathogenesis. AIM: To evaluate serum IL-33 in patients with asthma and healthy controls, and to evaluate the association of IL-33 with different asthma phenotypes. METHODS: Patients with asthma (n = 115) and healthy subjects (n = 85) were included in the study. Subjects with asthma were divided into groups according to their phenotype: allergic/non-allergic, eosinophilic/non-eosinophilic, obese/non-obese and severity according to GINA (mild, moderate and severe). The concentration of IL-33 in serum was measured by standardized enzyme-linked immunosorbent assay. RESULTS: The level of IL-33 was significantly higher in patients with asthma when compared to healthy subjects (672.73 ± 104.47 pg/mL vs 268.52 ± 27.56 pg/mL, P < 0.05). IL-33 was also higher in the allergic asthma group patients when compared to non-allergic asthmatics (844.61 ± 152.08 pg/mL vs 369.56 ± 77.94 pg/mL, P < 0.05). There was a significantly higher serum IL-33 level in the eosinophilic asthma group when compared to the group of non-eosinophilic asthma patients (1001.10 ± 199.11 pg/mL vs 337.49 ± 72.68 pg/mL, P < 0.01). We did not find a significant difference in serum IL-33 level between different asthma severity groups, obese and non-obese asthmatics. CONCLUSION: IL-33 is increased in asthma patients, particularly in some phenotypes: allergic asthma and eosinophilic asthma.

Role of Th22 and IL-22 in pathogenesis of allergic airway diseases: Pro-inflammatory or anti-inflammatory effect?

A new population of T cells known as Th22 was described for the first time in 2009. These cells are usually identified by the production of IL-22. However, this cytokine is also secreted by other cells such as Th1, Th2, Th17, natural killers, and innate lymphoid cells. Th22 is known as a pro-inflammatory agent in allergic skin diseases. Recently, more evidence has emerged showing associations between these cells and other diseases. The role of Th22 in asthma and allergic rhinitis is controversial: some authors suggest that Th22 has a pro-inflammatory effect, while others state that Th22 has anti-inflammatory properties. The aim of this article was to review the role of Th22 and IL-22 in allergic airway diseases based on the most recent literature. This review suggests that Th22 plays a significant role in the pathogenesis of allergic airway diseases and has predominantly anti-inflammatory properties. More studies are needed to clarify the role of Th22 in more detail.