A Quality-of-life Study in Patients with Anaphylaxis to Hymenoptera Venom in Iran.

Little is known about the quality of life of patients with anaphylaxis to Hymenoptera venom. The Vespid Allergy Quality of Life Questionnaire (VQLQ) is commonly used to assess the psychological burden of this condition. This study aimed to evaluate the validity and reliability of the Persian version of VQLQ. In this cross-sectional study, VQLQ was translated into Persian according to expert recommendations.  The final translated version of VQLQ was then administered to 115 patients with Hymenoptera venom allergy at an asthma and allergy clinic in Iran. More than half of the participants were between 20 and 40 years of age, and 60% were male. Fear, anxiety, and outdoor activities had the most significant impact on the quality of life of patients with Hymenoptera venom allergy. Additionally, quality of life was more affected in women than in men, while no correlation was found with age. Furthermore, the quality of life was affected by a history of acute anaphylactic shock due to Hymenoptera venom. The Persian version of VQLQ enables the measurement of quality of life in patients with Hymenoptera venom allergy in the Iranian population. The inclusion of VQLQ in the initial evaluation of these patients may potentially guide allergist in providing support for venom-specific immunotherapy.

The role of molecular diagnosis in anaphylactic patients with dual or triple-sensitization to Hymenoptera venoms.

BACKGROUND: The poly-sensitization to Hymenoptera venom makes it difficult to select genuine allergens for immunotherapy and increases patients' costs. The objective of this study was to determine the culprit allergen in dual or triple-sensitized patients to three Hymenoptera venoms through molecular diagnosis and evaluating the results of incorporating the molecular diagnosis with skin tests. METHODS: Thirty-two patients with anaphylactic reactions and dual or triple-sensitization to Hymenoptera venoms in skin tests entered this study. IgE-sensitization to whole extracts and molecules of Apis mellifera (Api m), Vespula vulgaris (Ves v), and Polistes dominulus (Pol d) was evaluated utilizing ALEX or ImmunoCAP. RESULTS: Twenty-nine patients (90.6%) were male. IgE-sensitization to at least one of the allergenic molecules related to Apis mellifera, Vespula vulgaris, and Polistes dominulus was seen in 59.4, 53.1, and 21.9%, respectively. Among 32 patients, 14 (43.8) and 8 (25%), were mono-sensitized to Api m and Ves v components in ALEX, respectively. Double sensitization to Hymenoptera was identified in 18.8% of patients in ALEX. Api m 1+/Api m 2-/Api m 10- and Ves v 1+/Ves v 5+ demonstrated the most prevalent sensitizations patterns in our patients. CONCLUSIONS: The molecular diagnosis of IgE-sensitization to Hymenoptera venoms can be valuable, especially in patients who show dual or triple-sensitization in skin tests, as the ALEX results revealed mono and double-sensitization to Hymenoptera venoms in 22 and 6 patients, respectively. Regarding the high cost and adverse reactions of venom immunotherapy, especially for two or three venoms, incorporating the molecular diagnosis alongside skin tests for accurate diagnosis of the culprit venom could help decrease costs for patients.

Immune endotyping and gene expression profile of patients with chronic rhinosinusitis with nasal polyps in the aspirin-exacerbated respiratory disease (AERD) and the non-AERD subgroups.

BACKGROUND: Chronic Rhinosinusitis (CRS) is a paranasal sinus inflammatory disease and is divided into two subgroups defined as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays a T helper (Th)2 biased phenotype, and based on sensitivity or tolerance to aspirin or non-steroidal anti-inflammatory drugs (NSAID), is further subdivided into Aspirin-exacerbated respiratory disease (AERD) and non-AERD groups. Considering the challenge of diagnosis and treatment in patients with CRSwNP, particularly the AERD subtype, and the significance of endotyping in these patients, we examined the immune profile and endotyping based on gene expression analysis in the AERD and the non-AERD groups of patients with CRSwNP. MATERIAL AND METHOD: In this study, 21 patients were enrolled and were categorized into AERD (N = 10) and non-AERD (N = 11) groups based on their sensitivity to aspirin. After the special washing period, nasal polyps were biopsied in both groups, and the infiltration of eosinophils, neutrophils, plasma cells, and lymphocytes was compared between the AERD and the non-AERD groups. Also, gene expression levels of transcription factors including Tbet, GATA3, RoRγt, and FoxP3 and inflammatory cytokines including interleukin (IL)1ß, IL1RAP (IL1 receptor accessory protein), IL2, IL4, IL5, IL10, IL13, IL17, TNFα, and IFNγ were investigated by quantitative Real-time PCR (qRT-PCR). Statistical analyses were performed using analytical tests including Kolmogorov-Smirnov, Mann-Whitney, and T-test. A P value less than 0.05 was considered statistically significant. RESULTS: The mean ± SD age of the studied groups was 37 ± 8.7 years old (21-50) for the AERD, and 40.4 ± 7.7 years old (31-52) for the non-AERD. LMS/EPOS/SNOT scores and pulmonary function tests showed no difference between the two groups. Serum immunoglobulin E (IgE) levels were found to be higher in patients with AERD (p = 0.04), however, the peripheral blood counts of eosinophils were comparable in the two groups. In the histopathologic analysis, the AERD group showed higher percentages of eosinophils (p = 0.04), neutrophils (p = 0.04), and plasma cells (p = 0.04) than the non-AERD group. Additionally, the gene expression levels of GATA3 (p = 0.001), IL4 (p = 0.04), IL5 (p = 0.007), and IL17 (p = 0.03) were significantly higher in the AERD than the non-AERD groups. CONCLUSION: Higher gene expression levels of GATA3, IL4, IL5, and IL17 were observed in the AERD group compared with the non-AERD group. These findings point to distinct patterns of inflammation in patients with AERD, with a predominance of Th2 inflammation.

From variant of uncertain significance to likely pathogenic in two siblings with atypical RAG2 Deficiency: a case report and review of the literature.

BACKGROUND: Severe combined immunodeficiencies (SCIDs) are hereditary disorders characterized by impaired T and B cell function, resulting in significant immune system dysfunction. Recombination-activating gene (RAG) mutations account for a substantial proportion of SCID cases. Here, we present two sibling cases of SCID caused by a novel RAG2 gene mutation. CASE PRESENTATION: The index case was an 8-year-old boy who had a history of recurring infections. After a comprehensive immunological workup, the initial diagnosis of agammaglobulinemia was revised to combined immunodeficiency (CID). The patient underwent hematopoietic stem cell transplantation (HSCT) but succumbed to cytomegalovirus (CMV) infection. His brother, a 4-month-old boy, presented with CMV chorioretinitis. Leaky SCID was diagnosed based on genetic tests and immunological findings. The patient received appropriate treatment and was considered for HSCT. Both siblings had a homozygous RAG2 gene variant, with the first case classified as a variant of uncertain significance (VUS). The presence of the same mutation in the second brother, and the clinical phenotype, supports considering the mutation as likely pathogenic. CONCLUSIONS: This case report highlights a novel RAG2 gene mutation associated with CID. The classification of a VUS may evolve with accumulating evidence, and additional studies are warranted to establish its pathogenicity. Proper communication between genetic counselors and immunologists, accurate documentation of patient information, increased public awareness, and precise utilization of genetic techniques are essential for optimal patient management.

Investigation of the Relationship between Aspirin-Sensitivity and Poor Response to Medical Management in NSAIDs-exacerbated Respiratory Disease Patients with Sinonasal Polyposis.

Background: NSAID-exacerbated respiratory disease (N-ERD) is a highly heterogeneous disorder with various clinical symptoms. The aspirin challenge test is a gold standard method for its diagnosis, and there are still no reliable in vitro diagnostic biomarkers yet. Oral challenge tests are time-consuming and may be associated with a risk of severe systemic reactions. This study aimed to evaluate whether patients with poor responses to medical management are more susceptible to being aspirin-sensitive. Methods: In this cohort study, after CT scanning of all patients and subject selection, conventional medical treatment was started as follows and continued for three consecutive months: at first, saline nose wash twice per day, intranasal beclomethasone spray one puff in each nostril twice per day, montelukast 10 mg tablet once daily, a ten-day course of oral prednisolone starting with the dose of 25 mg per day and taper and discontinued thereafter. Sinonasal outcome test 22 (SNOT22) was used for the evaluation of symptom severity. Statistical analyses were performed with SPSS version 23, and data were analyzed using an independent samples T-test, paired T-test, and Receiver operating curve analysis. Results: 25 males and 53 females were enrolled in this study, with an average age of 41.56 ± 11.74 years old (18-36). Aspirin challenge test results were positive in 29 (37.2%) patients. The average SNOT22 scores before the treatment were 52.97 ± 17.73 and 47.04 ± 18.30 in aspirin-sensitive and aspirin-tolerant patients, respectively, and decreased to 27.41 ± 16.61 and 24.88 ± 16.72 in aspirin-sensitive and aspirin-tolerant patients after the treatment, respectively. There was no significant difference in SNOT22 scores between the groups. Conclusion: The severity of symptoms before treatment and clinical improvement after treatment are not good predictors of N-ERD.

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.

Autoimmune versus Non-autoimmune Cutaneous Features in Monogenic Patients with Inborn Errors of Immunity.

Cutaneous manifestations are one of the most common presentations among patients with inborn errors of immunity (IEI). These skin manifestations are often among the first presenting features in the majority of patients preceding the IEI diagnosis. We studied 521 available monogenic patients with IEI listed in the Iranian IEI registry up to November 2022. We extracted each patient's demographic information, detailed clinical history of cutaneous manifestations, and immunologic evaluations. The patients were then categorized and compared based on their phenotypical classifications provided by the International Union of Immunological Societies. Most patients were categorized into syndromic combined immunodeficiency (25.1%), non-syndromic combined immunodeficiency (24.4%), predominantly antibody deficiency (20.7%), and diseases of immune dysregulation (20.5%). In total, 227 patients developed skin manifestations at a median (IQR) age of 2.0 (0.5-5.2) years; a total of 66 (40.7%) of these patients initially presented with these manifestations. Patients with cutaneous involvement were generally older at the time of diagnosis [5.0 (1.6-8.0) vs. 3.0 (1.0-7.0) years; p = 0.022]. Consanguinity was more common among patients who developed skin disorders (81.4% vs. 65.2%, p < 0.001). The overall skin infection rate and the type of dominant pathogens were significantly different among the IEI patients in different phenotypical classifications (p < 0.001). Atopic presentation, including urticaria, was highly prevalent among patients with congenital defects of phagocytes (p = 0.020). The frequency of eczema was also significantly higher among cases with both syndromic and non-syndromic combined immunodeficiency (p = 0.009). In contrast, autoimmune cutaneous manifestations, including alopecia and psoriasis, were most common in patients with immune dysregulation (p = 0.001) and defects in intrinsic or innate immunity (p = 0.031), respectively. The presence of autoimmune cutaneous complications significantly improved the survival rate of IEI patients (p = 0.21). In conclusion, cutaneous manifestations were observed in nearly 44% of Iranian patients with monogenic IEI. A considerable number of patients with cutaneous involvements developed these disorders as their first manifestation of the disease, which was particularly noticeable in patients with non-syndromic combined immunodeficiency and phagocytic defects. The neglected skin disorders in IEI patients might delay diagnosis, which is generally established within a 3-year interval from the development of skin-related problems. Cutaneous disorders, especially autoimmune features, might indicate a mild prognosis in IEI patients.

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.

Adsorption of heavy metals on natural zeolites: A review.

Water pollution has jeopardized human health, and a safe supply of drinking water has been recognized as a worldwide issue. The increase in the accumulation of heavy metals in water from different sources has led to the search for efficient and environmentally friendly treatment methods and materials for their removal. Natural zeolites are promising materials for removing heavy metals from different sources contaminating the water. It is important to know the structure, chemistry, and performance of the removal of heavy metals from water, of the natural zeolites to design water treatment processes. This review focuses on critical analyses of the application of distinct natural zeolites for the adsorption of heavy metals from water, specifically, arsenic (As(III), As(V)), cadmium (Cd(II)), chromium (Cr(III), Cr(VI)), lead (Pb(II)), mercury(Hg(II)) and nickel (Ni(II)). The reported results of heavy-metal removal by natural zeolites are summarized, and the chemical modification of natural zeolites by acid/base/salt reagent, surfactants, and metallic reagents has been analyzed, compared, and described. Furthermore, the adsorption/desorption capacity, systems, operating parameters, isotherms, and kinetics for natural zeolites were described and compared. According to the analysis, clinoptilolite is the most applied natural zeolite to remove heavy metals. It is effective in removing As, Cd, Cr, Pb, Hg, and Ni. Additionally, an interesting fact is a variation between the natural zeolites from different geological origins regarding the sorption properties and capacities for heavy metals suggesting that natural zeolites from different regions of the world are unique.

The Autoimmune Manifestations in Patients with Genetic Defects in the B Cell Development and Differentiation Stages.

PURPOSE: Primary B cell defects manifesting as predominantly antibody deficiencies result from variable inborn errors of the B cell lineage and their development, including impairments in early bone marrow development, class switch recombination (CSR), or terminal B cell differentiation. In this study, we aimed to investigate autoimmunity in monogenic patients with B cell development and differentiation defects. METHODS: Patients with known genetic defects in the B cell development and differentiation were recruited from the Iranian inborn errors of immunity registry. RESULTS: A total of 393 patients with a known genetic defect in the B cell development and differentiation (257 males; 65.4%) with a median age of 12 (6-20) years were enrolled in this study. After categorizing patients, 109 patients had intrinsic B cell defects. More than half of the patients had defects in one of the ATM (85 patients), BTK (76 patients), LRBA (34 patients), and DOCK8 (33 patients) genes. Fifteen patients (3.8%) showed autoimmune complications as their first manifestation. During the course of the disease, autoimmunity was reported in 81 (20.6%) patients at a median age of 4 (2-7) years, among which 65 patients had mixed intrinsic and extrinsic and 16 had intrinsic B cell defects. The comparison between patients with the mentioned four main gene defects showed that the patient group with LRBA defect had a significantly higher frequency of autoimmunity compared to those with other gene defects. Based on the B cell defect stage, 13% of patients with early B cell defect, 17% of patients with CSR defect, and 40% of patients who had terminal B cell defect presented at least one type of autoimmunity. CONCLUSION: Our results demonstrated that gene mutations involved in human B cell terminal stage development mainly LRBA gene defect have the highest association with autoimmunity.

Doxycycline Improves Quality of Life and Anosmia in Chronic Rhinosinusitis With Nasal Polyposis: A Randomized Controlled Trial.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex disorder and effective treatment remains a major challenge. Some antibiotics with anti-inflammatory properties are reported to have potential to be used as an adjunct therapy in the management of chronic airway inflammation. OBJECTIVE: The aim of this study was to evaluate the efficacy of doxycycline in CRSwNP. METHODS: In this randomized, double-blind, placebo-control study, we assessed the efficacy of doxycycline in patients with moderate to severe CRSwNP. A total of 100 patients were randomly assigned to receive either doxycycline (200 mg on the first day followed by 100 mg daily) or placebo for 6 weeks. All patients received baseline therapy with fluticasone, montelukast, and nasal irrigation during the study. The primary outcome was quality of life based on the sino-nasal outcome test (SNOT-22) questionnaire. We measured peak nasal inspiratory flow (PNIF) and severity of symptoms by visual analogue scale (VAS). Baseline blood eosinophil count, serum IgE level, eosinophil in nasal secretions, and Lund-Mackay score based on low dose paranasal CT scan were also recorded. RESULTS: Treatment with doxycycline significantly improved SNOT-22 (P = .037) and sense of smell (P = .048). The baseline SNOT-22 score had no effect on outcomes. The effect of doxycycline on quality of life in patients with or without nasal eosinophilia was not significantly different. Change in SNOT-22 score was also not correlated with serum IgE (P = .220, r = -0.186) and the eosinophil count (P = .190, r = -0.198). CONCLUSION: Doxycycline improves the quality of life in patients with CRSwNP. It also has temporarily beneficial effects in improving the sense of smell. The levels of eosinophil in the blood and nasal secretions do not affect the response to treatment. Hence, doxycycline can be used in both eosinophilic and non-eosinophilic nasal polyps.This study was registered at Iranian Registry of Clinical Trials. https://www.irct.ir/ IRCTID: IRCT20210403050817N1.

Diversity of malignancies in patients with different types of inborn errors of immunity.

Genetic defects in the development, maturation, and/or function of the immune cells can lead to Inborn errors of immunity (IEI) which may predispose patients to malignancies. The overall risk for cancer in children with IEI ranges from 4 to 25% and the type of malignancy is highly dependent on the specific mutant gene underlying IEI. We investigated 3056 IEI patients registered in the Iranian national registry between the years 1999 and 2020 in this retrospective cohort study. The frequency of malignancy and its association with the type of IEI in these patients were evaluated. A total of 82 IEI patients with malignancy were enrolled in this study. Among them, predominantly lymphoma was the most common type of malignancy (67.1%), followed by leukemia (11%), and cancers of the head and neck (7.3%). Among identified lymphoma cancers, non-Hodgkin's lymphomas were the most frequent type (43.9%) followed by different subtypes of Hodgkin's lymphoma (23.2%). Solid tumors (18.3%) appeared to be very heterogeneous by type and localization. The correlation between the type of malignancy and survival status and the association between the type of malignancy and IEI entities were unremarkable. The awareness of the association between the presence of IEI and cancer highlights the importance of a synergistic effort by oncologists and immunologists in the early diagnosis of malignancy and personalized therapeutic strategies in IEI patients.

Autoimmunity in monogenic combined immune deficiencies with associated or syndromic features.

Background: Combined immune deficiencies (CIDs) with associated or syndromic features are a highly heterogeneous subgroup of inherited immune disorders. These patients represent specific clinical complications with an increased risk of autoimmune conditions. Methods: We analyzed data of monogenic patients with syndromic CIDs adopted from the Iranian inborn errors of immunity registry up to January 2022. A comprehensive comparison in terms of demographic, clinical, and immunological features was performed between patients with and without autoimmunity and also among four mutation groups with the most registered cases including ATM, STAT3 (AD-LOF), DNMT3B/ZBTB24, and WAS mutations. Results: A total of 137 patients with monogenic syndromic CIDs were included. Most commonly mutated genes were the ATM [80 (58.4%)] and STAT3 (AD-LOF) [19 (13.9%)], followed by DNMT3B [11 (8%)], and WAS [11 (8%)]. More than 18% of all patients with syndromic CIDs, including most DNMT3B/ZBTB24 mutations patients, were clinically diagnosed with antibody deficiencies before genetic evaluation. Patients with ATM and WAS mutations had the latest age of onset and the lowest age of diagnosis, respectively. Autoimmune disorders were diagnosed in 24 patients at a median age of 3.5 (2.6-6.0) years, 70.6% of which were diagnosed prior to the diagnosis of immunodeficiency. Lymphoproliferation, particularly hepatosplenomegaly, was significantly higher in patients with autoimmunity (p=0.004). Syndromic CID patients with autoimmunity had significantly lower IgG levels. Hematologic autoimmunity mainly immune thrombocytopenic purpura was the most frequent autoimmunity among major groups of ATM, STAT3 (AD-LOF), DNMT3B/ZBTB24, and WAS mutations, however ATM-mutated patients present more diversified involved organs including rheumatologic, gastrointestinal and dermatologic autoimmunity. Conclusion: About 18% of patients with monogenic syndromic CIDs developed autoimmunity, mainly in the form of hematological immune diseases. Autoimmunity could be an early-onset involvement with a potential diagnostic impact on suspicious cases of syndromic CIDs.

The Uncomplicated Course of COVID-19 in Primary Immunodeficiency Patients: A Report of 14 Common Variable Immunodeficiency Patients.

Coronavirus disease 2019 (COVID-19) affects millions of people worldwide. Clinical manifestations range from asymptomatic to severe viral pneumonia. CVID patients with COVID-19 infection are not adequately studied. In some studies, CVID patients had higher mortality rates, although other studies showed that CVID patients might have an uncomplicated COVID-19 infection. We describe 14 cases of COVID-19 infection in Iranian CVID patients in this study, including clinical manifestations, laboratory findings, and treatment strategies. There were 29% of patients with mild disease, 43% with moderate disease, and 29% with severe disease in this study. A critical case and a death occurred in none of our patients. There were six cases of infection more than two weeks after receiving the second dose of Sinopharm BIBP COVID-19 vaccine; all had mild to moderate disease. Among these patients, Remdesivir was the most frequently prescribed medication. According to this study, most of our patients presented with an uncomplicated disease course.

Neonatal Onset of Hemophagocytic Lymphohistiocytosis Due to Prenatal Varicella-Zoster Infection in a Neonate with Griscelli Syndrome Type 2.

Type 2 Griscelli syndrome (Type2 GS) is a primary inborn error of the immune system, classified in the immune dysregulation group.1,2 There are three different types of the disease, with different genetic causes responsible for the autosomal recessive inheritance pattern. Although hypopigmentation is common in all variants, neurological involvement or immunodeficiency with varying severity is seen in different types. Molecular motor protein myosin 5 an (MYo5A) [Type1GS], guanosine Triphosphate (GTP) binding protein (RAB27A) [Type2GS], and mutation in human melanophilin (MLPH) [Type 3GS] which is limited to hypopigmentation are reported as the known genetic defects in GS.3 Severe, ineffective, and uncontrolled inflammatory reactions are referred to as the pathogenesis of Hemophagocytic lymphohistiocytosis (HLH). HLH is a life-threatening condition that can be defined as either primary or secondary. Secondary causes happen in the context of autoimmunity, malignancy, spontaneous, or infections.4 Prenatal infections play an important role in causing long-term complications in the fetus. Some of them include toxoplasmosis, rubella, cytomegalovirus, herpes simplex, and other organisms including syphilis, parvovirus, and Varicella zoster, known as TORCH syndrome (5).TORCH has been well described for a long time but there are limited reports of developing HLH in the context of prenatal infections. We described a type 2GS syndrome with neonatal-onset HLH triggered by a prenatal infection.

The Effectiveness of Oral Immunotherapy in Patients with Sesame Anaphylaxis using Omalizumab.

OBJECTIVE: Sesame allergy is the most prevalent allergy to seeds. Oral immunotherapy (OIT) is defined as continuous consumption of an allergen at special doses and time. Omalizumab (Anti-IgE) increases tolerance to allergens used in OIT. This study evaluated the effectiveness of a new sesame OIT protocol in patients with sesame anaphylaxis in combination with omalizumab. METHODS: In this prospective open-label interventional trial study, 11 patients with a history of sesame anaphylaxis were enrolled after confirmation by oral food challenge (OFC) test. At baseline, skin prick test (SPT) and skin prick to prick (SPP) test were performed. Serum sesame-specific IgE (sIgE) levels were measured. The maintenance phase was continued at home with daily sesame intake for 4 months. At the end of month 4, the OFC and above-mentioned tests were repeated to evaluate the treatment effectiveness. RESULTS: All 11 patients who underwent sesame OIT after 4 months could tolerate a dietary challenge of 22 ml tahini (natural sesame seed, equal to 5,000 mg of sesame protein and higher) and the average of wheal diameter in the SPT and SPP tests significantly decreased after desensitization. CONCLUSION: This OIT protocol may be a promising desensitization strategy for patients with sesame anaphylaxis. Also, omalizumab appears to have reduced the severity of reactions.

Progressive multifocal leukoencephalopathy in a patient with novel mutation in the RAC2 gene: a case report.

BACKGROUND: Progressive multifocal leukoencephalopathy is a rare demyelinating disease that is often secondary to lytic destruction of oligodendrocytes and, to a lesser extent, to astrocytes' response to human neurotrophic John Cunningham polyomavirus. Any underlying congenital disorder of primary or secondary immunodeficiency may predispose to virus infection and possible invasion of the brain. We present the first reported case of progressive multifocal leukoencephalopathy due to a mutation in the RAC2 gene. CASE PRESENTATION: We describe the case of a 34-year-old Iranian man with recurrent infections from the age of 2 years, along with other disorders such as nephritic syndrome, factor XI deficiency, and hypogammaglobulinemia. He was treated regularly with intravenous immunoglobulin from the age of 10 years with a diagnosis of common variable immune deficiency. Genetic testing confirmed a novel homozygous mutation in the RAC2 gene in the patient. Owing to the onset of neurological symptoms a few months ago, the patient was completely avaluated, which confirmed the diagnosis of PML. Despite all efforts, the patient died shortly after progression of neurological symptoms. CONCLUSIONS: According to previous studies, progressive multifocal leukoencephalopathy has been associated with 26 cases of primary immunodeficiency. Our patient presents a new case of primary immunodeficiency with progressive multifocal leukoencephalopathy. Accurate examination of these cases can help us to gain insight into the immune response to John Cunningham virus and better treat this potentially deadly disease.

Immunochemical Characterization of Ligustrum Vulgare (Privet) Pollen Allergens: Study of Common Allergenic Plant in Iran.

Ligustrum vulgare (Privet) pollen proteins are responsible for allergies in susceptible individuals in many regions of the world. This study investigated the immunochemical characterization of Privet pollen extract and the occurrence of skin prick test reactivity to Privet and other allergenic pollen grains in allergic rhinitis patients. All subjects experienced a skin prick test with twenty-two allergen extracts. sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) separated Privet pollen extract, IgE-immunoblotting, and specific ELISA procedures determined the allergenic profile on forty-five Privet allergic patients. A positive allergic reaction to L. vulgare pollen extract was observed in forty-five (31.4%) out of 145 patients. Ten resolved protein fractions were found on SDS-PAGE, ranging from 10 to 80 kDa. IgE-specific antibodies interacted with several allergenic protein bands from Privet-allergic patients in the immunoblotting assay. The most significant interaction was observed in proteins with molecular weights of approximately 15, 18, 43, and 66 kDa. Privet pollen is regarded as a potent allergen composed of IgE-binding constituents. Considering the high allergenicity of Privet pollen grains and since many countries are rich in this plant, identification and production of recombinant forms of common allergens in this species can be used for developing more efficient diagnostic, therapeutic, and preventive approaches.

Recalcitrant Cutaneous Warts in a Family with Inherited ICOS Deficiency.

Recalcitrant warts, caused by human papillomaviruses (HPVs), can be a cutaneous manifestation of inborn error of immunity. This study investigated the clinical manifestations, immunodeficiency, single-gene susceptibility, and HPV repertoire in a consanguineous family with severe sinopulmonary infections and recalcitrant warts. Clinical and immunologic evaluations, including FACS and lymphocyte transformation test, provided evidence for immunodeficiency. Combined whole-exome sequencing and genome-wide homozygosity mapping were utilized to disclose candidate sequence variants. Whole-transcriptome sequencing was used to concomitantly investigate the HPV genotypes and the consequences of detected sequence variants in the host. The proband, a male aged 41 years, was found to be homozygous for the c.6delG, p.Lys2Asnfs∗17 variant in ICOS, encoding the inducible T-cell costimulator. This variant was located inside the 5 megabase of runs of homozygosity on 2q33.2. RNA sequencing confirmed the deleteriousness of the ICOS variant in three skin biopsies revealing significant downregulation of ICOS and its ligand, ICOSLG. Reads unaligned to the human genome were applied to 926 different viruses, and α-HPV57, ß-HPV107, ß-HPV14, and ß-HPV17 were detected. Collectively, we describe a previously unrecognized inborn error of T-cell immunity to HPVs, indicating that autosomal recessive ICOS deficiency can underlie recalcitrant warts, emphasizing the immunologic underpinnings of recalcitrant warts at the nexus of human and viral genomic variation.

Severe Persistent Eczema in a Recipient of the Gam-COVID-Vac vaccine.

Since the beginning of the COVID-19 pandemic, efforts have been made to design safe and effective vaccines against SARS-CoV-2. Numerous vaccines have been designed and tested in limited clinical trials in various countries. Among them, the Sputnik V vaccine has shown a relatively safe profile and, to our knowledge, has no associated major side effects. We describe the case of a 40-year-old female healthcare worker who developed severe persistent eczematous lesions on the second day after she received the first dose of the Sputnik vaccine. The eczematous lesions were refractory to an antihistamine and persisted at the 1 month follow-up. Severe persistent eczematous lesions should be viewed as a potential side effect of vaccination with the Sputnik V vaccine. Moreover, a severe allergic reaction to a COVID-2019 vaccine may indicate the vaccine is ineffective in the recipient. LEARNING POINTS: Vaccination against COVID-19 may be accompanied by rare complications.Eczematous lesions can be a side effect of the Sputnik V vaccine.A severe allergic reaction to a COVID-19 vaccine may result in decreased vaccine effectiveness in the recipient.