Determining reference ranges for lymphocyte proliferation responses to phytohemagglutinin and Bacillus Calmette-Guérin in Iranian children.

PURPOSE: To establish reference ranges (RRs) for stimulation index of T cell proliferation triggered by phytohemagglutinin (PHA-SI) and Bacillus Calmette-Guérin (BCG-SI). METHODS: This study investigated data from 359 healthy children and 35 patients with cellular immunodeficiency as positive controls (2010-2021). We applied a colorimetric-based method (BrdU) to measure proliferation and determine the RRs at the 2.5th and 97.5th percentiles (95% confidence intervals). A cross-validation approach was performed. RESULTS: In healthy controls, the RRs for PHA-SI and BCG-SI ranged between 3 and 5.2 and 2.52 to 5.2, respectively. PHA-SI and BCG-SI were in Severe Combined Immunodeficiency (SCID) patients from 1.2 to 2.5 and 0 to 2, while in Mendelian susceptibility to mycobacterial diseases (MSMD) patients, 2.53 to 4.5 and 0.74 to 2.2, respectively. The thresholds' accuracy was checked for testing reference intervals with diagnostic effects. CONCLUSION: This study establishes PHA-SI and BCG-SI reference ranges to aid in diagnosing and treating congenital immunodeficiency diseases.

Cycle Threshold Values Predict COVID-19 Severity and Mortality but Are not Correlated with Laboratory Markers.

Many studies have evaluated the possible utility of cycle threshold (Ct) values as a predictor of Coronavirus disease 2019 (COVID-19) severity and patient outcome. Given the inconsistent results, we aimed to evaluate the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Ct values and disease severity, inflammatory markers, and outcomes in Iranian patients with COVID-19. A retrospective study of 528 patients with COVID-19 hospitalized from September 2020 to October 2021 was conducted. Demographic, clinical, and laboratory data of patients were retrieved from electronic medical records. Ct values were analyzed as a continuous variable after subcategorizing into 3 groups: low (Ct values<20), medium (Ct values 20 to 30), and high (Ct values>30). Of the 528 patients (45.1% female) aged 13 to 97 years, 109 patients had low Ct values, 312 patients had medium, and 107 patients had high Ct values. Patients with low Ct values were more likely to present with critical COVID-19, require invasive mechanical ventilation and develop complications such as acute respiratory distress syndrome and pneumonia. Furthermore, patients with low or medium Ct values were more likely to die compared to patients with high Ct values. Multivariate analysis showed that patients with low or medium Ct values were more likely to have severe COVID-19 compared with patients with high Ct values. The multivariate analysis also showed a higher risk of mortality in patients with low Ct values compared to patients with high Ct values, although this was not statistically significant. Our findings revealed that Ct values were an independent predictor of COVID-19 severity. The risk of mortality was higher in patients with low Ct values. However, further investigation is needed to address the correlation between Ct values and inflammatory factors.

Antibody Production after COVID-19 Vaccination in Patients with Inborn Errors of Immunity.

Background: Few studies have evaluated COVID-19 vaccine efficacy in patients with inborn errors of immunity (IEI). Objective: To evaluate the levels of antibody (Ab) production and function after COVID-19 vaccination in IEI patients with phagocytic, complement, and Ab deficiencies and their comparison with healthy controls. Methods: Serum samples were collected from 41 patients and 32 healthy controls at least one month after the second dose of vaccination, while clinical evaluations continued until the end of the third dose. Levels of specific anti-receptor-binding domain (RBD) IgG and anti-RBD neutralizing antibodies were measured using EUROIMMUN and ChemoBind kits, respectively. Conventional SARS-CoV-2 neutralization test (cVNT) was also performed. Cutoff values of ≤20, 20-80, and ≥80 (for cVNT and Chemobined) and 0.8-4.2, 4.2-8.5, and ≥8.5 (for EUROIMMUN) were defined as negative/weak, positive/moderate, and positive/significant, respectively. Results: A considerable distinction was observed between the Ab-deficient patients and the controls for Ab concentration (EUROIMMUN, p<0.01) and neutralization (ChemoBind, p<0.001). However, there was no significant difference compared with the other patient groups. A near-zero cVNT in Ab-deficient patients was found compared to the controls (p<0.01). A significant correlation between the two kits was found using the whole data (R2=0.82, p<0.0001). Conclusion: Despite varying degrees of Ab production, all Ab deficient patients, as well as almost half of those with complement and phagocytic defects, did not effectively neutralize the virus (cVNT). In light of the decreased production and efficiency of the vaccine, a revised immunization plan may be needed in IEI.

Clinical, immunological and molecular findings of 8 patients with typical and atypical severe combined immunodeficiency: identification of 7 novel mutations by whole exome sequencing.

Severe combined immunodeficiency (SCID) is one of the severe inborn errors of the immune system associated with life-threatening infections. Variations in SCID phenotypes, especially atypical SCID, may cause a significant delay in diagnosis. Therefore, SCID patients need to receive an early diagnosis. Here, we describe the clinical manifestations and genetic results of four SCID and atypical SCID patients. All patients (4 males and 4 females) in early infancy presented with SCID phenotypes within 6 months of birth. The mutations include RAG2 (p.I273T,p.G44X), IL7R (p.F361WfsTer17), ADA (c.780+1G>A), JAK3 (p.Q228Ter), LIG4 (p.G428R), and LAT (p.Y207fsTer33), as well as a previously reported missense mutation in RAG1 (p.A444V). The second report of LAT deficiency in SCID patients is presented in this study. Moreover, all variants were confirmed in patients and their parents as a heterozygous state by Sanger sequencing. The results of our study expand the clinical and molecular spectrum associated with SCID and leaky SCID phenotypes and provide valuable information for the clinical management of the patients.

Clinical and immunological characteristics of 69 leukocyte adhesion deficiency-I patients.

BACKGROUND: In order to support the comprehensive classification of Leukocyte Adhesion Deficiency-I (LAD-I) severity by simultaneous screening of CD11a/CD18, this study assessed clinical, laboratory, and genetic findings along with outcomes of 69 LAD-I patients during the last 15 years. METHODS: Sixty-nine patients (40 females and 29 males) with a clinical phenotype suspected of LAD-I were referred to Immunology, Asthma, and Allergy research institute, Tehran, Iran between 2007 and 2022 for further advanced immunological screening and genetic evaluations as well as treatment, were enrolled in this study. RESULTS: The diagnosis median age of the patients was 6 months. Delayed umbilical cord separation was found in 25 patients (36.2%). The median diagnostic delay time was 4 months (min-max: 0-82 months). Forty-six patients (66.7%) were categorized as severe (CD18 and/or CD11a: below 2%); while 23 children (33.3%) were in moderate category (CD18 and/or CD11a: 2%-30%). During the follow-ups, 55.1% of children were alive with a mortality rate of 44.9%. Skin ulcers (75.4%), omphalitis (65.2%), and gingivitis (37.7%) were the most frequent complaints. Genetic analysis of the patients revealed 14 previously reported and three novel pathogenic mutations in the ITGB2 gene. The overall survival of patients with and without hematopoietic stem cell transplantation was 79.3% and 55.6%, respectively. CONCLUSION: Physicians' awareness of LAD-I considering delayed separation of umbilical cord marked neutrophilic leukocytosis, and variability in CD11 and CD18 expression levels, and genetic analysis leads to early diagnosis and defining disease severity. Moreover, the prenatal diagnosis would benefit families with a history of LAD-I.

Molecular findings and clinical manifestations of 18 Iranian children with Griscelli syndrome type 2: Two novel homozygote mutations in RAB27A gene in a patient.

Griscelli syndrome type 2 (GS2) is an autosomal recessive immunodeficiency characterized by hair hypopigmentation, recurrent fever, hepatosplenomegaly and pancytopenia. This study aims to find new genetic changes and clinical features in 18 children with GS2 caused by the RAB27A gene defect. In all, 18 Iranian children with GS2 who presented with silver grey hair and frequent pyogenic infection were included in this study. After recording demographic and clinical data, PCR sequencing of the RAB27A gene was performed for all exons and exon-intron boundaries. Two patients in this study were subjected to whole-exome sequencing followed by Sanger sequencing. Light microscopy study of hair showed large irregular clumps of pigment with the absence of giant granules on the blood smear. Mutation analysis of the RAB27A gene identified two novel missense mutations as homozygous in a patient, one in exon 2, c.140G>C and another in exon 4, c.328G>T. In addition, for 17 other patients, 6 reported mutations were obtained including c.514_518delCAAGC, c.150_151delAGinsC, c.400_401delAA, c.340delA, c.428T>C and c.221A>G. The mutation c.514_518delCAAGC was the most frequent and found in 10 patients; this mutation may be considered a hotspot in Iran. Early diagnosis and treatment of RAB27A deficiency can contribute to better disease outcomes. In affected families, genetic results could be urgently needed to make a timely decision about haematopoietic stem cell transplantation and prenatal diagnosis.

The Risk of the Next Child Getting Affected by Chronic Granulomatous Disease in Families with at Least One Autosomal Recessive CGD Child.

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder more common in autosomal recessive (AR) than X-linked in Iran. This study aimed to assess whether having a child with AR-CGD would increase the likelihood of the next child being affected by CGD. Ninety-one families with at least one child affected by AR-CGD entered this study. Out of the 270 children, 128 were affected by AR-CGD. We used a cross tab for the odds ratio (OR) calculation, in which exposure to a previously affected child and the next child's status were evaluated. This study illustrated that the chances of having another child afflicted with AR-CGD are significantly increased if the previous child had AR-CGD (OR=2.77, 95% CI=1.35-5.69).Althoug h AR disorders affect 25% of each pregnancy, we showed that the chance that the next child would be affected by CGD, given that the previous child was affected, is 2.77 times greater than in families with a normal child. It is recommended to warn families with one or more affected children to evaluate the risk of CGD in their subsequent pregnancies with prenatal diagnosis.

Human genetic defects in SRP19 and SRPRA cause severe congenital neutropenia with distinctive proteome changes.

The mechanisms of coordinated changes in proteome composition and their relevance for the differentiation of neutrophil granulocytes are not well studied. Here, we discover 2 novel human genetic defects in signal recognition particle receptor alpha (SRPRA) and SRP19, constituents of the mammalian cotranslational targeting machinery, and characterize their roles in neutrophil granulocyte differentiation. We systematically study the proteome of neutrophil granulocytes from patients with variants in the SRP genes, HAX1, and ELANE, and identify global as well as specific proteome aberrations. Using in vitro differentiation of human induced pluripotent stem cells and in vivo zebrafish models, we study the effects of SRP deficiency on neutrophil granulocyte development. In a heterologous cell-based inducible protein expression system, we validate the effects conferred by SRP dysfunction for selected proteins that we identified in our proteome screen. Thus, SRP-dependent protein processing, intracellular trafficking, and homeostasis are critically important for the differentiation of neutrophil granulocytes.

Confirmation of Hyperimmunoglobulin E Syndrome in Two Patients with an Ocular Problem: Detection of Two New DOCK8 Mutations.

Early diagnosis of primary immunodeficiencies is crucial for timely treatment and preventing unwanted complications. Next-generation sequencing (NGS) and detailed clinical and immunological evaluation can help early detect such disorders. This study aimed to confirm the diagnosis of two cases of autosomal recessive hyper-immunoglobulin E (IgE) syndrome (AR-HIES), presenting with irreversible eye involvement. Two unrelated patients with suspected AR-HIES were referred to the Immunology, Asthma and Allergy Research Institute (IAARI), Tehran, Iran. Immunological screening tests were performed for AR-HIES, which showed elevated serum IgE levels, eosinophilia, and low T-lymphocyte responses. NGS was performed, and the results were confirmed by Sanger sequencing. Sequence analysis showed a mutation in intron 17 of the dedicator of cytokinesis 8 (DOCK8) gene in the first patient, and a homozygous three base-pair deletion in exon 45 of DOCK8 in the second patient. This is the first time such mutations are reported and these variants are predicted to be damaging. Both patients suffered from persistent viral infections along with cytomegalovirus (CMV) retinitis. Suspicion of these two novel DOCK8 mutations can benefit patients presenting with recalcitrant ophthalmic viral involvements and relevant immunological test results. This would lead to earlier referrals for immunologic and genetic confirmation and thus, a more timely intervention with hematopoietic stem cell transplantation (HSCT).

Molecular profile of specific IgE to allergenic components in allergic adults using allergen nano-bead array.

BACKGROUND: An increasing interest in the field of molecular diagnosis of allergy has been developed in recent years and it goes to be as the routine in vitro protocol in allergy diagnosis. friendly allergen nano-bead array (FABER) is a new multiplex assay for the evaluation of specific IgE against 244 allergens including whole extracts and allergenic molecules. The research intended to assess the pattern of IgE sensitization to allergenic components of allergens in allergic adults using FABER 244. METHODS: Sixty patients with allergic diseases entered this cross-sectional study. Specific IgE to 122 whole allergens extracts and 122 allergenic components were assessed using an allergen nano-bead array (FABER) for all patients. This test includes inhalant and food allergens. RESULTS: Thirty-seven patients were male (61.7%). The mean (SD) age of patients was 30.73(±6.87) years. As the allergen nano-bead array results showed, Lolium perenne (63.3%), Phleum pratense (60%) and Platanus acerifolia (51.7%) were considered as the most common IgE sensitizations to the aeroallergen extracts. Moreover, Lol p 1, Phl p 1.0102 and Cup a 1 were found as the most frequent allergenic components in our allergic patients. Among protein families, CCD-bearing proteins, expansin, cysteine protease and profilin families illustrated the highest allergic sensitization. CONCLUSIONS: The results of the present study demonstrated that despite the higher prevalence of sensitization to Salsola kali (47.2%) using extract-based assays in the previous phase of this research, allergenic components of grasses (Lol p 1, Phl p 1.0102), Cup a 1 as well as Sal k1 as the major components of Cupressuss arizonica and Salsola kali showed the higher sensitization, respectively, in adults' allergic patients using FABER test.

Human Neutrophil Antigen Genotype and Allele Frequencies in Iranian Blood Donors.

OBJECTIVE: Human neutrophil antigens (HNAs) can be targeted by HNA-allo antibodies and cause a variety of clinical conditions such as transfusion-related acute lung injury (TRALI) and neonatal alloimmune neutropenia (NAIN). The current study is aimed at identifying the genotype and allele frequencies of HNAs in Iranian blood donors. METHODS: A total of 150 blood samples were obtained from healthy blood donors. HNA-1, HNA-3, HNA-4, and HNA-5 were genotyped, using the polymerase chain reaction sequence-specific primer (PCR-SSP) technique. The expression of the HNA-2 antigen on the neutrophil surface was evaluated by flow cytometry. RESULTS: The allele frequencies of FCGR3B∗1 (encoding HNA-1a), FCGR3B∗2 (encoding HNA-1b), and FCGR3B∗3 (encoding HNA-1c) were 0.34, 0.63, and 0.03, respectively. For HNA-3, the allele frequencies for SLC44A2∗1 (encoding HNA-3a) and SLC44A2∗2 (encoding HNA-3b) were 0.63 and 0.37, respectively. The frequencies of ITGAM∗1 (encoding HNA-4a) and ITGAM∗2 (encoding HNA-4b) alleles were 0.85 and 0.15, respectively. Furthermore, the frequencies of ITGAL∗1 (encoding HNA-5a) and ITGAL∗2 (encoding HNA-5b) alleles were 0.72 and 0.28, respectively. In the studied population, HNA-2 antigen was present on the neutrophil surface in 97.3% of the individuals, while no detectable HNA-2 expression was observed in 2.7% of the individuals. However, no significant difference in HNA-2 expression between different age groups was found. CONCLUSION: The present study provides the first report of the HNA allele and genotype frequencies among the Iranian population. All HNAs (HNA-1 to HNA-5) were typed using the PCR-SSP and flow cytometer. In the current cohort study, the determined HNA allele frequencies were similar to the previous reports from British, German, and Danish populations. Considering the presence of different Iranian ethnic groups, further studies with a larger sample size are needed to draw a total picture for HNA allele frequencies.

A fludarabine and melphalan reduced-intensity conditioning regimen for HSCT in fifteen chronic granulomatous disease patients and a literature review.

Chronic granulomatous disease (CGD) is a life-threatening immunodeficiency condition. To date, hematopoietic stem cell transplantation (HSCT) is the only curative modality. We prospectively studied the outcomes of fifteen CGD patients undergoing HSCT with fludarabine and melphalan plus anti-thymocyte globulin (ATG). Most of the donors were fully matched siblings (n = 12). Cyclosporine A and methylprednisolone were used for graft-versus-host disease (GVHD) prophylaxis. CGD diagnosis had been suspected upon clinical symptoms and was confirmed in all patients by an abnormal neutrophil functional assay. The three-year overall survival (OS) and event-free survival (EFS) rates were 73.3% and 46.7%, respectively. With the median follow-up time of 33.12 months, the mean OS and EFS were 42.6 and 26.8 months; respectively. Eleven patients (73.33%) achieved full donor chimerism. Two stable mixed chimerisms with no sign of the underlying disease (13.33%) and two secondary graft failure (13.33%) occurred as well. The cumulative incidence of transplant-related mortality was 23.1% and it was two times more in adults compared with children. Three years GVHD-FS (free survival) was 57.8% in all patients and it was 70% and 42.9% in children and adults, respectively. Our results indicate that fludarabine, melphalan, and ATG have relatively favorable outcomes in CGD patients. Also, we suggest that HSCT should be performed as soon as a suitably matched donor is found.

Genetic Study of Hereditary Angioedema Type I and Type II (First Report from Iranian Patients: Describing Three New Mutations).

BACKGROUND: Hereditary Angioedema (HAE) is a rare autosomal dominant immunodeficiency disease with mutation in C1 inhibitor gene (SERPING1) which deficient and dysfunction of C1-INH protein result in HAE type I or type II, respectively. The present study aimed to define the genetic spectrum of HAE type I and type II among Iranian patients. METHODS: Thirty-four patients with clinical phenotype of recurrent edematous attacks in face, upper and lower limbs, hands, and upper airway entered the study. Mutations in SERPING1 were analyzed using PCR and Sanger Sequencing. In addition, Multiplex Ligation-dependent Probe Amplification (MLPA) was performed to discover large deletions or duplications in negative screening samples by Sanger. RESULTS: Twenty-three patients were diagnosed with HAE type I and 11 with HAE type II. Fourteen distinctive pathogenic variations including five frameshift (p.G217Vfs*, p.V454Gfs*18, p.S422Lfs*9, p.S36Ffs*21, p.L243Cfs*9), seven missense (p.A2V, p.G493R, p.V147E, p.G143R, p.L481P, p.P399H, p.R466C), one nonsense (p.R494*), and one splicing defect (C.51 + 2 T˃C), which three of these mutations were identified novel. However, no mutation was found in seven patients by Sanger sequencing and MLPA. CONCLUSION: Final diagnosis with mutation analysis of HAE after clinical evaluation and assessment of C1INH level and function can prevent potential risks and life-threatening manifestations of the disorder. In addition, genetic diagnosis can play a significant role in facilitating early diagnosis, pre-symptomatic diagnosis, early diagnosis of children, asymptomatic cases, and those patients who have the borderline biochemical results of C1-INH deficiency and/or C4.

Exposure to road noise and asthma prevalence in adults.

Noise has been reported as one of the most important risk factors for asthma, but there are some disagreements. This study aimed to investigate the effect of road noise on asthma prevalence in adults. In the current study, 3172 adults were interviewed through the ECRHS standardized questionnaire in Tehran, the capital of Iran. Exposure to road noise was assessed considering distance of individual participants from the noise monitoring stations via the spatial analysis in GIS software. Logistic regression was used to assess the effect of noise on the symptoms of asthma. Findings showed a significant positive association between wheezing with dyspnea as the best marker for asthma and noise levels at daytime (OR 1.03; 0.98-1.05) and nighttime (OR 1.05; 0.84-1.09). Also, a significant positive association was obtained between daytime and nighttime noise levels and other asthma symptoms including wheezing, nocturnal chest tightness, nocturnal dyspnea, wheezing without cold, nocturnal cough, and asthma medication. Association between current asthma and noise level was not significant. There was a significant association between population age and current asthma prevalence (P = 0.001). Therefore, chronic exposure to road noise especially in the nighttime could increase asthma prevalence. So, control of noise sources can be suggested to diminish asthma in adults.

Identification of Antibodies against Neutrophil Surface Antigens in Two Iranian Patients with Autoimmune Neutropenia.

Autoimmune neutropenia is a type of immune-mediated neutropenia, caused by antibody-induced neutrophil destruction. Here we report two cases (3-year-old boy and 9-year-old girl) with suspected autoimmune neutropenia. The presence of neutrophil antibodies in sera of these patients was investigated using standard neutrophil antibody screening tests such as granulocyte immunofluorescence test (GIFT), granulocyte agglutination test (GAT), and lymphocyte immunofluorescence test (LIFT). A positive reactivity with two panel cells was found in GIFT. No reactivities with panel cells were observed in GAT and LIFT. To the best of our knowledge, this is the first report for detecting the neutrophil reactive antibodies using genotyped neutrophils in patients with autoimmune neutropenia in Iran. The final diagnosis of our patients was primary autoimmune neutropenia for the boy and autoimmune neutropenia associated with familial Mediterranean fever for the girl.

Immunological effects of convalescent plasma therapy for coronavirus: a scoping review.

BACKGROUND: Preliminary studies revealed the safety and effectiveness of convalescent plasma (CP) therapy for patients with coronavirus. In this study, we aimed to evaluate and summarize the available evidence on CP therapy, identify the research gap regarding the immunological response to CP therapy and pave the road for future studies. METHODS: This study was conducted according to the Hilary Arksey and Lisa O'Malley framework. To find out the relevant studies, we searched PubMed, Scopus and Embase databases up to 30th May 2021. Data have been extracted according to three categories: (1) patients' characteristics, (2) clinical and immunological responses to CP therapy and (3) pre-infusion screening of the CP samples. RESULTS: A total of 12,553 articles were identified. One hundred fifty-four studies met the inclusion criteria for full-text review. More than half of the included studies (112 studies, (75.6%)) concluded satisfactory outcomes and or safety of CP infusion in patients. Results of studies showed the efficacy of CP therapy in clinical improvement (101 studies), decreasing in the level of inflammatory factors (62 studies), elimination or decreasing in viral load (60 studies), and induction or increase in antibody response (37 studies). Despite these promising results, the results of the 49 studies revealed that CP therapy was ineffective in the survival of patients, clinical improvement, viral infection elimination or decrease in the inflammatory factor levels. Furthermore, the adaptive immune response was evaluated in 3 studies. Information related to the pre-infusion screening for human leukocyte antigen/human neutrophil antigen (HLA/HNA) antibodies was not reported in most of the studies. Our gap analysis revealed that the influence of the CP infusion on the adaptive immune and inflammatory responses in patients with coronavirus needs further investigation. CONCLUSIONS: Based on the results of most included studies, CP infusion was safe and resulted in clinical improvement of patients and decreasing the viral load. The effect of the CP infusion on adaptive immune response and inflammatory cytokines in patients with coronavirus needs further investigation.

Meatal Stenosis and Atopic Condition: A Pilot Study Demonstrating a Possible Unidentified Etiology.

Meatal stenosis (MS) is known as one of the most frequent complications of circumcision. In the present study, we aimed to find any possible relationship between MS and allergic disorders. A total of 36 children with a mean±SD age of 5.84±2.03 years were referred with MS and an atopic background even in themselves or in one of their family members (Group A). There were also age-matched controls with a mean±SD age of 5.70±2.17 years who were referred to our center with allergic symptoms and no urinary complaints (Group B, n=17). The RIDA qLine allergy and allergy explorer (ALEX) tests were performed for all patients to find possible allergen sensitization. Laboratory findings revealed that IgE-sensitization to the main food and aeroallergens in Group A (with the chief complaint of MS in whom a mild atopic condition was found during concise medical history taking) were very similar to the control group with no significant difference (except for ryegrass which was higher in the control group). Although total IgE level was considerably higher in group B compared to group A, food sensitization to cow's milk and ß-lactoglobulin was higher in asthmatic patients of group A compared to the controls. It seems that not all patients with MS should be considered as a complication of circumcision and undergo a surgical procedure for correction of the stenosis. Further investigations are required to determine the role of concise medical history taking and proper treatment of the allergic disorder to reduce failed surgical attempts in atopic boys with MS.

Investigating the Variation of TREC/KREC in Combined Immunodeficiencies.

T-cell receptor excision circles (TREC)/Kappa-deleting recombination excision circles (KREC) assay has been recently recognized for detecting patients with primary (T- and/or B-cell) immunodeficiency (PID). We aimed to investigate the alterations of these biomarkers in some combined immunodeficiency patients compared to the healthy controls in different age groups. TREC and KREC were assessed in a total of 82 PID patients, most of them with exact genetic diagnosis (3 months to 42 years); using quantitative real-time-polymerase chain reaction (PCR). Patients had a final diagnosis of common variable immunodeficiency (n=23), ataxia-telangiectasia (AT) (n=17), hyper-IgE syndrome (HIES) (7 with DOCK8 deficiency, 4 with signal transducer and activator of transcription 3 (STAT3) deficiency, and 8 children with unknown genetic defects), Wiskott-Aldrich syndrome (WAS) (n=20), purine nucleoside phosphorylase (PNP)deficiency(n=1), dedicator of cytokinesis2 (DOCK2) deficiency (n=1), recombinase activating gene1 (RAG1) deficiency (n=1). Very low to zero amounts of TREC and/or KREC were detected in 14 out of 23 cases of common variable immunodeficiency (CVID), 14 out of 17 cases of AT, 8 out of 20 cases of WAS, 6 out of 7 cases of DOCK8-deficiency patients, 4 out of 8 cases of HIES with unknown genetic defects and all patients with defects in DOCK2, PNP, and RAG1. STAT3-deficient patients were normal for both biomarkers. All patients showed a significant difference in both markers compared to age-matched healthy controls. Our findings highlight that apart from severe types of T/B cell defects, this assay can also be used for early diagnosis the patients with late-onset of disease and even PIDs without a positive family history.

A Pilot Study on Controlling Coronavirus Disease 2019 (COVID-19) Inflammation Using Melatonin Supplement.

No effective antiviral drugs and vaccines are available for the treatment of patients with severe coronavirus 2019 (COVID-19). Therefore, available, safe, and inexpensive drugs and supplements such as melatonin are among the proposed options for controlling inflammation. We did a randomized, single-blind study in Imam Khomeini Hospital between June 30, 2020, and August 5, 2020. Mild to moderate COVID-19 patients aged 25-65 years were eligible to enter the study based on chest CT scan, clinical symptoms, and physician diagnosis. The intervention group was prescribed 6 mg of oral melatonin for 2 weeks, which consumed half an hour before bedtime every night in low light conditions. Clinical symptoms and C-reactive protein (CRP) were measured before and after treatment in the melatonin received and control (regular medications) groups. Among screened patients with COVID-19, 14 patients were assigned to receive melatonin, and 17 patients were considered as controls. A significant difference (p=0.005) between CRP 1 and CRP 2 levels (before and after using melatonin) was found in the melatonin group while this difference (p=0.069) was not significant in the control group. Also, the percentage of recovery (based on symptoms) in patients who took melatonin was higher than that of patients in the control group (85.7% VS 47.1%). The result of this study confirmed the effectiveness of melatonin in mild to moderate outpatients with COVID-19. More clinical trials on elderly, diabetic, obese patients and severe cases are suggested in future studies.

Investigating the relationship between particulate matter and inflammatory biomarkers of exhaled breath condensate and blood in healthy young adults.

Inflammatory biomarkers in exhaled breath condensate (EBC) are measured to estimate the effects of air pollution on humans. The present study was conducted to investigate the relationship between particulate matter and inflammatory biomarkers in blood plasma and exhaled air in young adults. The obtained results were compared in two periods; i.e., winter and summer. GRIMM Dust Monitors were used to measure PM10, PM2.5, and PM1 in indoor and outdoor air. A total of 40 healthy young adults exhaling air condensate were collected. Then, biomarkers of interleukin-6 (IL-6), Nitrosothiols (RS-NOs), and Tumor necrosis factor-soluble receptor-II (sTNFRII) were measured by 96 wells method ELISA and commercial kits (HS600B R&D Kit and ALX-850-037-KI01) in EBC while interleukin-6 (IL-6), sTNFRII and White Blood Cell (WBC) were measured in blood plasma in two periods of February 2013 (winter) and May 2013 (summer). Significant association was found between particulate matter and the white blood cell count (p < 0.001), as well as plasma sTNFRII levels (p-value = 0.001). No significant relationship was found between particulate matter with RS-NOs (p = 0.128), EBC RSNOs (p-value = 0.128), and plasma IL-6 (p-value = 0.167). In addition, there was no significant relationship between interleukin-6 of exhaled air with interleukin-6 of plasma (p-value < 0.792 in the first period and < 0.890 in the second period). sTNFRII was not detected in EBC. Considering the direct effect between increasing some biomarkers in blood and EBC and particulate matter, it is concluded that air pollution causes this increasing.