A modified schedule of multiple aeroallergen ultra-rush immunotherapy in perennial allergic rhinitis: safety, efficacy, and T lymphocyte cell population studies.

BACKGROUND: This study assessed whether a modified immunotherapy schedule for allergic rhinitis could be safe and efficient. Ultra-rush immunotherapy (URIT) rapidly desensitizes patients to aeroallergens. OBJECTIVE: We aimed to develop a modified URIT protocol in 3 days to achieve the target dose while observing whether it could improve this situation and decrease the time to achieve the maintenance dose. METHODS: The URIT was exercised in 21 patients with perennial allergic rhinitis. Premeditations were given to the patients 3 days prior to the immunotherapy and during the 3 days injections immunotherapy: pred nisolone, ranitidine, and Airokast/montelukast. Finally, the T cell population frequencies of patients prior to and after immunotherapy, including T helper 1, T helper 2, cytotoxic T lymphocytes, and regulatory T cells, were studied using flow cytometry. During the URIT protocol, 21 patients received 291 injections. RESULT: Six patients (28.6%) showed systemic reactions in our study. All systemic reactions occurred on the third day by the 1:1 dilution of the maintenance dose. These systemic reactions occurred in three patients after 13 injections, and the three remaining patients showed systemic reactions following the last injection. No systemic reaction was observed on the first and second day of the therapy, and the risk of systemic reaction with every injection was about 2%. Among the T cell populations, CD3+ and CD8+ cells decreased significantly. CONCLUSION: The findings emphasized that URIT, alongside premedication with a high dose of antihistamine, helped to achieve the maintenance dose and control clinical manifestations.

The impact of propolis on clinical manifestations and specific IgE levels against salsola in perennial-allergic rhinitis patients.

Objectives: Propolis has an anti-inflammatory effect induced by inhibiting cyclooxygenase, subsequent inhibition of prostaglandin and nitric oxide synthesis, reduction of inflammatory cytokines, and eventually immunosuppressive activity [1-3]. This study aims to evaluate the impact of propolis on clinical features and specific IgE levels against salsola in perennial allergic rhinitis patients. Methods: Thirty patients diagnosed with perennial allergic rhinitis with salsola-positive skin prick test were enrolled in this randomized controlled clinical trial and divided into two groups. The intervention group received the propolis (200 mg per day), and the control group received a placebo for four months, besides intranasal corticosteroids. At baseline and the end of the intervention, the level of Salsola-specific IgE was measured by the RAST method. To assess the propolis effect on the quality of life and disease severity, miniRQLQ and SNOT22 questionnaires were completed by patients before and after the intervention. Results: According to Table 1, Serum IgE level showed decreasing changes (-0.057) despite increasing changes in the control group (1.039). However, these differences were not statistically significant (P = 0.967). Based on the miniRQLQ questionnaire, quality of life improved in both groups without any significant difference (P = 0.930). According to the SNOT-22 questionnaire, both groups' nasal and sinus problems decreased significantly. However, the intervention type did not affect this decrease and was observed over time in both groups (P> 0.05). Conclusion: Propolis supplementation did not significantly affect various laboratory parameters, clinical symptoms, and quality of life of patients with allergic rhinitis.

Exploring Common Symptoms in Patients with Respiratory Allergies Using K-Means Algorithm in the North-East of Iran in 2012-2015.

Background: As a common disease among people of almost any age, allergic rhinitis has many adverse effects such as lowering the quality of life and efficiency at work or school. Considering these conditions and the collection of large amounts of data, the present research was conducted on allergic rhinitis and asthma patients' data to extract the common symptoms of these diseases using cluster analysis and the k-means algorithm. Materials and Methods: The present cross-sectional research was conducted in Mashhad city. The inclusion criteria were affliction with one or two respiratory allergy diseases diagnosed by an allergy specialist through clinical history taking and physical examination. A researcher-made checklist was used in the present study for data collection. Then, the K-means algorithm's cluster analysis model was conducted to extract clusters (WEKA software (3, 6, 9)). Results: Overall, 1,231 patients met the inclusion criteria. The result of the Cluster analysis consisted of Cluster 1 in allergic rhinitis consisted of 702 patients, and cluster 2 consisted of 382 patients.46 asthma patients were assigned to cluster 1 and 23 to cluster 2.Also, 60 asthma and allergic rhinitis patients were assigned to cluster 1 and 19 to cluster 2. The most common symptoms in all patients were rhinorrhea, sneezing, nasal congestion, and itchy nose. Conclusion: Overall, Salsola kali was the most common allergen in allergic rhinitis and asthma patients. Also, the most common symptoms in patients are rhinorrhea, sneezing, itchy nose, and nasal congestion. This study can help physicians diagnose allergic rhinitis and asthma in geographical areas with a high prevalence of Salsola kali.

The role of synbiotics as adjunctive agents in the treatment of allergic rhinitis: A randomized controlled trial.

Introduction: Allergic rhinitis (AR) is a prevalent chronic disease affecting a significant portion of the global population. The substantial economic burden associated with treating AR necessitates the exploration of alternative therapies. Probiotics have gained attention due to their availability, minimal adverse effects, and cost-effectiveness. The present study aims to investigate the role of synbiotics as adjunctive agents in the treatment of AR when added to standard treatment. Method: Thirty patients with persistent allergic rhinitis (PAR) were randomly assigned to receive routine diet therapy plus synbiotics or routine diet therapy plus placebo per day for 4 months. The data analysis was conducted using SPSS Version 20. Result: This study revealed a notable difference in immunoglobulin (Ig)E levels between the placebo and synbiotics groups (p = 0.035) following the intervention. Although a statistically significant difference (p = 0.039) was observed in the changes before and after the intervention (synbiotics and placebo) in the SNOT22 questionnaire, this finding was not observed for the MiniRQLQ questionnaire. For the MiniRQLQ questionnaire, the within-group analysis showed significant changes in activity variables (p = 0.023), ocular symptoms (p = 0.036), and practical problems (p = 0.043) exclusively in the synbiotics group. Additionally, changes in nasal symptoms were observed in both synbiotics (p = 0.006) and placebo (p = 0.007) groups. Conclusion: This study suggests that synbiotics supplementation for 4 months can impact IgE levels compared with placebo in individuals with PAR, while also exhibiting positive effects on symptomology.

The Effect of Glasthma Syrup in Asthma: a study protocol for a triple-blind randomized controlled trial.

Objectives: Asthma is a chronic disease, and the demand for herbal medicines in this field has increased in recent years. The new findings highlight the role of the gut-lung axis in the pathophysiology of asthma. Hence, this study will evaluate the safety and efficacy of Glasthma syrup, an herbal formula based on Persian medicine, in improving asthma and regulating intestinal permeability. The formula consists of five herbal ingredients that have anti-inflammatory effects on the respiratory tract, also known as gut tonics. Methods: The study will be conducted as a placebo-controlled, triple-blind, randomized trial. It will consist of a 4-week intervention followed by a 4-week follow-up period. The target sample size is 20 patients with moderate asthma aged 18 to 60 years. Eligible participants will be randomly assigned to either the experimental group or the control group in equal numbers. Patients in the experimental group will take Glasthma syrup (7.5 mL, twice a day), while patients in the control group will take a matching placebo. Both groups will receive a 4-week combination of a long-acting beta2 agonist and a leukotriene modulator as standard of care. Inhaled corticosteroids can be used as rescue medication as needed. Results: The primary outcomes are asthma symptom scale, lung function, and intestinal permeability. Secondary outcomes include quality of life, symptom recurrence rates, and blood tests. A safety assessment will also be conducted during the trial. Conclusion: In this trial, the effects of Glasthma syrup in patients with moderate asthma will be examined. The study will also assess the effects of the formulation on the gut-lung axis by simultaneously monitoring the gut permeability index, asthma symptoms, and lung function.

COVID-19 cases, hospitalizations and deaths after vaccination: a cohort event monitoring study, Islamic Republic of Iran.

Objective: To investigate the incidence of coronavirus disease 2019 (COVID-19) cases, hospitalizations and deaths in Iranians vaccinated with either AZD1222 Vaxzevria, CovIran® vaccine, SARS-CoV-2 Vaccine (Vero Cell), Inactivated (lnCoV) or Sputnik V. Methods: We enrolled individuals 18 years or older receiving their first COVID-19 vaccine dose between April 2021 and January 2022 in seven Iranian cities. Participants completed weekly follow-up surveys for 17 weeks (25 weeks for AZD1222) to report their COVID-19 status and hospitalization. We used Cox regression models to assess risk factors for contracting COVID-19, hospitalization and death. Findings: Of 89 783 participants enrolled, incidence rates per 1 000 000 person-days were: 528.2 (95% confidence interval, CI: 514.0-542.7) for contracting COVID-19; 55.8 (95% CI: 51.4-60.5) for hospitalization; and 4.1 (95% CI: 3.0-5.5) for death. Compared with SARS-CoV-2 Vaccine (Vero Cell), hazard ratios (HR) for contracting COVID-19 were: 0.70 (95% CI: 0.61-0.80) with AZD1222; 0.73 (95% CI: 0.62-0.86) with Sputnik V; and 0.73 (95% CI: 0.63-0.86) with CovIran®. For hospitalization and death, all vaccines provided similar protection 14 days after the second dose. History of COVID-19 protected against contracting COVID-19 again (HR: 0.76; 95% CI: 0.69-0.84). Diabetes and respiratory, cardiac and renal disease were associated with higher risks of contracting COVID-19 after vaccination. Conclusion: The rates of contracting COVID-19 after vaccination were relatively high. SARS-CoV-2 Vaccine (Vero Cell) provided lower protection against COVID-19 than other vaccines. People with comorbidities had higher risks of contracting COVID-19 and hospitalization and should be prioritized for preventive interventions.

Prognostic Value of Serum MICA Levels as a Marker of Severity in COVID-19 Patients.

The COVID-19 global pandemic and high mortality rates necessitate the development of diagnostic and prognostic tools, as well as expanding testing capacity. Existing methods for detecting and characterizing SARS-CoV-2 infection are typically based on viral genome detection or measuring COVID-19-specific antibody levels. Despite their value, these methods are unable to predict disease outcomes in patients. Given the critical role of innate immune cells, particularly natural killer (NK) cells, in antiviral defense, this study sought to determine the prognostic value of serum secretory MHC class I polypeptide-related sequence A (sMICA) levels as an essential ligand for the NKG2D receptor, the master regulator of NK cell development and responsiveness. Serum MICA levels were measured by ELISA assay. Sera (n = 60) from SARS-CoV-2 positive patients were collected, and disease severity was determined using clinical criteria. The patient group included 30 patients with mild disease and 30 severely ill patients, as well as 30 healthy controls. Our findings revealed that serum MICA levels were significantly higher in patients than in controls, especially in cases with severe complications (P < .0001). Higher serum MICA levels may be associated with respiratory failure in COVID-19 and may serve as a marker of clinical severity in patients infected with SARS-CoV-2, particularly when clinical manifestations are insufficient to make a confident prediction.

Higher MICA levels may be associated with respiratory failure in COVID-19 infection.SMICA levels change with age, particularly for patients with severe COVID-19 disease.NKG2D ligands may have prognostic and therapeutic value for COVID-19 patients.

Comparison of Serum Total IgA Levels in Severe and Mild COVID-19 Patients and Control Group.

BACKGROUND: The present study aimed to compare serum total IgA levels between severe and mild COVID-19 patients' groups and the control group. METHODS: In this cross-sectional study, 216 definite severe COVID-19 patients (as the inpatient group), 183 subjects with positive specific COVID-19 IgG with mild or no symptoms as the (outpatient group), and 203 healthy subjects with negative specific serology, as the control group were investigated. The cases' laboratory data were collected, and thereafter, statistical tests, including independent samples t test, ANOVA test, and post hoc test, were performed using SPSS software version 22. RESULT: The mean ± SD of IgA in all the included subjects was 2.23 ± 0.78 (g/L). According to the obtained results, there were statistically significant changes in IgA among the three study groups (P value < 0.05). This difference was significant between both outpatient and inpatient groups (P value < 0.05). The mean ± SD of serum IgG in all the subjects was calculated as 15.83 ± 5.73 (g/L). A strong statistically significant change was also seen in IgG among all three groups (P value < 0.001). Of note, there was a significant negative correlation between IgG and IgA total titers of the outpatient group (P value = 0.011*r = - 0.188). CONCLUSION: It was shown that the total serum IgA and IgG levels are significantly associated with the severity of COVID-19 infection. As well, we found that total serum IgA and IgG are associated with the severity of illness. Since a low level of IgA is asymptomatic and high frequent in Iran and other countries, we suggest the evaluation of serum IgA levels in high-risk people and strengthening immune system in subjects with a low level of IgA, in order to reduce the rate of death. In this regard, oral or nasal mucosal vaccines in combination with parenteral vaccination are recommended due to increasing immunity versus COVID-19 by further secretion of the IgA antibody and preventing virus transmission.

Total antioxidant capacity as a marker of severity of COVID-19 infection: Possible prognostic and therapeutic clinical application.

The pathogenesis of SARS-CoV-2 infection, causative pathogen of the known COVID-19 pandemic is not well clarified. In this regard oxidative stress is one of the topics that need to be investigated. Therefore, the present research was performed to explore the relationship between the oxidant/antioxidant system and COVID-19 exacerbation. Sera were collected from 120 patients with COVID-19 infection and 60 healthy volunteers as the control group. The patient group consisted of 60 cases with mild disease and 60 severely ill patients. Serum levels of total antioxidant capacity (TAC) and nitric oxide (NO) as well as serum activities of the two main antioxidant defense enzymes, superoxide dismutase (SOD) and catalase (CAT), were measured. TAC levels were considerably lower in patients compared with healthy individuals (p < 0.05) and also between patients with mild and severe diseases (p < 0.05). A rather decreasing trend was also found in NO concentration as well as SOD and CAT activity, though, the observed differences were not statistically significant (p > 0.05). These findings suggest that COVID-19 patients may be susceptible to depleted total antioxidant capacity. Moreover, showing such variations in blood samples of infected individuals could be considered as a predictive marker of COVID-19 severity.

Detection of Lophomonas blattarum (Order: Hypermastigida) from Iranian Patients with Allergic Rhinitis.

Background: Allergic rhinitis (AR) is one of the most common allergic diseases triggered by indoor and outdoor allergens. Certain arthropods, such as mites and cockroaches, contain protozoa like Lophomonas blattarum in their intestines to help with digestion that may have some role in AR. We aimed to determine the frequency of L. blattarum in nasal smears of patients with AR in comparison with healthy controls. Methods: In this prospective cross-sectional study (March 2015-March 2016), 36 patients with a clinical presentation of AR (with a positive prick test including mites) and 34 normal controls were included at ear, nose, and throat (ENT) clinic at Imam Reza Hospital of Mashhad, Iran. Nasal secretions were evaluated to examine presence of L. blattarum in the patients and control group by direct method. Diagnosis of L. blattarum was based on microscopic observation both on direct smear and Giemsa stained specimens. Results: Patients with AR had a higher frequency of L. blattarum in their nasal smears than the control group (25% vs. 2.9%) (P=0.001). Conclusion: We found L. blattarum more frequently in the nasal secretion of AR patients compared with healthy subjects; this protozoon may have some role in this condition. However, the relationship between L. blattarum and AR requires further studies to allow a greater understanding.

Epidemiology, Sociodemographic Factors and Comorbidity for Allergic Rhinitis, Asthma, and Rhinosinusitis Among 15 to 65-year-Old Iranian Patients.

Background: It is well established that upper and lower airways are often clumped together when diagnosing and treating a disease. This study was designed to determine the prevalence of upper and lower airway diseases and to assess the effect of sociodemographic factors on the prevalence and the comorbidity of these disorders. Methods: This cross-sectional population-based study included patients with ages ranging between 15 to 65 years, who were referred to allergy outpatient clinics in various provinces of Iran from April to September 2020. A modified global Allergy and Asthma European Network (GA2LEN) screening questionnaire was filled out by local allergists of the 12 selected provinces in Iran. Information about the patients and sociodemographic factors was also recorded. Statistical analysis was done by univariate statistical analyses and multiple logistic regressions in SPSS software Version 26. Results: Out of 4988 recruited patients, 1078 (21.6%) had the symptoms of allergic rhinitis (AR) and 285 (5.7%) met the criteria of asthma. The prevalence of acute rhinosinusitis (ARS) and chronic rhinosinusitis (CRS) was 21.6 % and 22%, respectively. The highest prevalence of AR and ARS was in Tehran with the arateof of 33.9% each. Asthma was more prevalent in Khuzestan (14.2%) and CRS in Baluchestan (57.5%). Our analysis showed that the patients with asthma were most likely to have other allergic diseases as well-CRS (OR = 4.8; 95% CI, 2.02- 5.82), AR (OR= 2.5, 95% CI, 2.10-3), ARS (OR = 1.8; 95% CI, 2.10-3), followed by eczema (OR = 1.4; 95% CI, 1.13-1.67).We found that those individuals with CRS were most likely to have painkiller hypersensitivity (OR= 2.1; 95% CI, 1.21-3.83). Furthermore, smoking has been found more than 1.5 folds in patients with ARS. After adjusting variables, there was no correlation between education, occupation, and ethnicity with the studied diseases. Conclusion: Rhinosinusitis is a common condition among Iranian patients. This study confirmed that inflammation of the upper and lower airways can occur simultaneously. Gender, education, occupation, and ethnicity were found to be irrelevant in the development of either AR, asthma, ARS, or CRS.

Evaluation of the Reliability and Validity of the Persian Version of Urticaria Control Test (UCT).

The urticaria control test (UCT) is a patient-reported outcome measure (PROM) for chronic urticaria (CU) patients. As a Persian version of the UCT was not available, the present research aimed to develop such a version, to test its reliability and validity as well as to evaluate urticaria control among Persian-speaking patients. This research was conducted at the Urticaria Centre of Reference and Excellence (UCARE) of Ghaem Hospital, Mashhad, Iran. In a first step, a linguistically validated Persian version of the UCT was developed through a structured forward and backward translation process and subsequent cognitive debriefing interviews. In a second step, the Persian version of the UCT was completed by 100 well-characterized CU patients together with two anchor instruments, the Chronic Urticaria Quality of life Questionnaire (CU-Q2oL) and the urticaria activity score (UAS), to obtain information on its internal consistency reliability and convergent validity. The Persian version of the UCT was found to have acceptable internal consistency reliability with a Cronbach's alpha coefficient of 0.68. In addition, the results obtained with the Persian UCT correlated with the CU-Q2oL total score (-0.48, p<0.001) and the UAS (-0.404, p˂0.001), suggesting convergent validity. Virtually all patients had poorly controlled CU (UCT<12). A Persian version of the UCT is now available and may help to improve the assessment and monitoring of disease control in Persian-speaking CU patients and to optimize treatment decisions.

Significant association between Taq1 gene polymorphism in vitamin D receptor and chronic spontaneous urticaria in the Northeast of Iran.

OBJECTIVE: Chronic spontaneous urticaria (CSU) is defined as urticaria with an unknown etiology which persists for more than 6 weeks. CSU is an uncomfortable cutaneous condition that occurs due to an immune-mediated inflammatory reaction. Many studies have demonstrated that vitamin D deficiency and single-nucleotide polymorphisms in the vitamin D receptor (VDR) impact the immune response. In the current study, the frequency of the Taq1 polymorphism in the VDR gene were compared between patients with CSU and individuals without CSU. METHODS: In a case-control study, a group of CSU patients (n = 100) was compared with a group of healthy age- and gender-matched individuals as a control group (n =100) who visited our center between 2015 and 2017. After DNA extraction from EDTA-containing blood, polymerase chain reaction (PCR-RFLP) was used to determine the presence of the Taq1 polymorphism. Serum vitamin D levels were measured using ELISA method (Abcam, Cambridge, USA). RESULTS: Genotyping for Taq1 polymorphism showed that TT, Tt and tt genes frequency in the CSU group were 36%, 54%, and 10% respectively. The TT, Tt and tt genotypes had a distribution of 50%, 47% and 3% respectively in the control group. The mean serum vitamin D level in the CSU group was 19.88 ± 8.14 ng/ml, which was not significantly correlated with the Taq1 polymorphism (P = 0.841). There was a significant relationship between Taq1 gene polymorphism (tt genotype) and CSU (P = 0.038). Tt genotype increased the risk of CSU (odds ratio = 1.596), and inheritance of tt genotype increased the risk even further (odds ratio = 4.630). CONCLUSION: The frequency of Taq1 genotype polymorphism in the VDR gene was significantly higher in patients with CSU compared to the control group. The tt genotype polymorphism may be a risk factor for CSU.

Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity.

BACKGROUND: The inborn errors of immunity (IEIs) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections besides other complications including autoimmune and inflammatory diseases. In this study, we aim to evaluate clinical, immunologic, and molecular data of monogenic IEI patients with and without autoimmune manifestations. METHODS: We have retrospectively screened cases of monogenic IEI in the Iranian PID registry for the occurrence of autoimmunity and immune dysregulation. A questionnaire was filled for all qualified patients with monogenic defects to evaluate demographic, laboratory, clinical, and molecular data. RESULTS: A total of 461 monogenic IEI patients (290 male and 171 female) with a median (IQR) age of 11.0 (6.0-20.0) years were enrolled in this study. Overall, 331 patients (72.1%) were born to consanguineous parents. At the time of the study, 330 individuals (75.7%) were alive and 106 (24.3%) were deceased. Autoimmunity was reported in 92 (20.0%) patients with a median (IQR) age at autoimmune diagnosis of 4.0 (2.0-7.0) years. Sixteen patients (3.5%) showed autoimmune complications (mostly autoimmune cytopenia) as the first presentation of the disease. Most of the patients with autoimmunity were diagnosed clinically with common variable immunodeficiency (42.4%). The frequency of sinusitis and splenomegaly was significantly higher in patients with autoimmunity than patients without autoimmunity. In patients with autoimmunity, the most common pathogenic variants were identified in LRBA (in 21 patients, 23.0%), ATM (in 13 patients, 14.0%), and BTK (in 9 patients, 10.0%) genes. In the evaluation of autoimmunity by different genes, 4 of 4 IL10RB (100%), 3 of 3 AIRE (100%), and 21 of 30 LRBA (70.0%) mutated genes had the highest prevalence of autoimmunity. CONCLUSIONS: Autoimmune phenomena are common features among patients with monogenic IEI and are associated with a more complicated course of the disease. Therefore, when encountering autoimmune disorders, especially in the setting of dysgammaglobulinemia, it would be appropriate to conduct next-generation sequencing to discover responsible genes for the immune dysregulation at an early stage of the disease.

Effect of Two Educational Models including Face-to-Face and Training Pamphlets for Disease Control in Asthmatic Patients.

BACKGROUND: Asthma is a common condition in which the patient requires self-management and teaching programs that lead to reduced prevalence and mortality. The main aim of this study was to improve the management knowledge of the disease through the use of educational tools, pamphlets and face-to-face lecture, concurrent with evaluating and comparing its effectiveness in response to treatment. MATERIALS AND METHODS: In this study, 82 asthmatic patients were enrolled. Training necessary to control the disease and use of drugs were provided to patients in one group by pamphlets (39 patients) and the other by face-to-face education (43 patients). After a month, Disease control examination and Asthma Control Test (ACT) scores were evaluated and compared. RESULTS: The mean age of participants was 39.12±14.25 years. There was no significant difference between the two groups in age, gender and education (P> 0.05) and no significant difference in asthma control between the two groups before the intervention (P = 0.065). The overall asthma control score in the pamphlet was increased from 15.43±4.99 at baseline to 20.58±4.47 in the assessment after one month education (P <0.001) and in face-to-face training an overall score was increased from 13.27±5.39 to 21.95±2.77 (P <0.001). After one month education, asthma control score was increased 5.23 ± 6.88 in pamphlets group and 8.9 ± 6.32 in face-to-face group (P = 0.014). CONCLUSION: Evaluation of both educational methods showed face-to-face training is more efficient.

Global systematic review of primary immunodeficiency registries.

INTRODUCTION: During the last 4 decades, registration of patients with primary immunodeficiencies (PID) has played an essential role in different aspects of these diseases worldwide including epidemiological indexes, policymaking, quality controls of care/life, facilitation of genetic studies and clinical trials as well as improving our understanding about the natural history of the disease and the immune system function. However, due to the limitation of sustainable resources supporting these registries, inconsistency in diagnostic criteria and lack of molecular diagnosis as well as difficulties in the documentation and designing any universal platform, the global perspective of these diseases remains unclear. AREAS COVERED: Published and unpublished studies from January 1981 to June 2020 were systematically reviewed on PubMed, Web of Science and Scopus. Additionally, the reference list of all studies was hand-searched for additional studies. This effort identified a total of 104614 registered patients and suggests identification of at least 10590 additional PID patients, mainly from countries located in Asia and Africa. Molecular defects in genes known to cause PID were identified and reported in 13852 (13.2% of all registered) patients. EXPERT OPINION: Although these data suggest some progress in the identification and documentation of PID patients worldwide, achieving the basic requirement for the global PID burden estimation and registration of undiagnosed patients will require more reinforcement of the progress, involving both improved diagnostic facilities and neonatal screening.

Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity.

BACKGROUND: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. METHODS: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children's Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. RESULTS: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0%) patients. Two patients (7.7%) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7%) developed one type of autoimmunity, and 16 patients (59.3%) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0%) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6%). In 13 patients (61.9%), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7%), gastrointestinal (48.1%), rheumatologic (25.9%), and dermatologic (22.2%) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. CONCLUSION: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity.

High proviral load of human T cell lymphotropic virus type-1 facilitates coronary artery diseases.

OBJECTIVES: Coronary artery disease (CAD) is known as a life threatening disease, worldwide. In this study the role of HTLV-1 infection was evaluated on cardiac involvement in an endemic region of northeastern Iran. MATERIALS AND METHODS: Serologic and molecular tests for HTLV-1 infection were carried out in subjects who had coronary angiography. A real-time PCR, TaqMan method, to quantify HTLV-1 proviral load (PVL), and routine hematological and biochemical tests were performed for study subjects. RESULTS: Twenty nine patients were HTLV-1+CAD+ and 13 cases were HTLV-1+CAD-. Although, there were no significant differences for risk factors like FBS, HDL, triglyceride, systolic and diastolic blood pressure (Cbp, Dbp), waist circumference (WC), hip circumference (WL), cholesterol (P=0.003), and LDL (P=0.007) levels, and monocyte count (P=0.05) had meaningful differences. The mean HTLV-1 PVL in HTLV-1+CAD+ subjects was 992.62±120 which was higher compared with HTLV-1+CAD- group (406.54±302 copies/104 PBMCs). Moreover, HTLV-1 PVL in males (833±108) was lower compared with females (1218±141 copies/104 PBMCs) (P=0.05). Patients with HTLV-1-PVL of more than 500 copies/104 had more diffused atherosclerosis plaque than patients with less than 500 (OR=6.87, 95% CI=1.34-35.05; P=0.016). Furthermore, patients with diffused coronary atherosclerosis had significantly higher levels of HTLV-1 PVL than patients with middle, proximal, and normal location of coronary sclerotic lesions (P<0.05). CONCLUSION: Taken together, in endemic area, HTLV-1 infection, more likely is a facilitating factor for heart complications and the high HTLV-1 PVL might affect CAD manifestations.