Allergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology最新文献

Objectives: Immunoglobulin A deficiency (IgAD) is a common disease with an unknown genetic defect, characterized by the decreased or absent IgA with other isotypes normal, normal subclasses, and specific antibodies. Patients with this disorder represent a spectrum of clinical manifestations including infections, autoimmune disorders, malignancy, and allergic diseases. The current study aimed to evaluate their prevalence and categorized them.

Methods: We searched PubMed, Web of Science, and Scopus databases to find eligible studies from the earliest available date to January 2022 with standard keywords. Pooled estimates of clinical manifestations prevalence and the corresponding 95% confidence intervals were calculated using random-effects models.

Results: The most prevalent clinical manifestations belonged to infection (64.8%) followed by allergic diseases (26.16%) and autoimmunity (22.0%), respectively. In selective IgA deficiency patients as the largest group of IgAD in current study, celiac disease (6.57%), Inflammatory bowel disease (4.01%), and rheumatoid arthritis (3.80%) were the most prevalent autoimmunity. Meanwhile, the most frequent infection was respiratory tract infection, fungal infection, and gastrointestinal infection at 50.74%, 18.48%, and 15.79%, respectively. In addition, the pooled prevalence of asthma, allergic rhinitis, and allergic conjunctivitis were 19.06%, 15.46%, and 11.68%, respectively which were reported as the most widespread allergic diseases.

Conclusions: Our results showed that apart from undiagnosed IgAD patients, IgAD patients represent a wide range of clinical manifestations. Infection, allergy, and autoimmunity are the most common clinical manifestations. The concurrent presence of IgA and IgG subtypes deficiency could be associated with increased susceptibility to infection. Considering the probability of developing new clinical complications during follow-up, periodic assessments of IgAD patients should be inspected.

The market share of foods carrying labels suggesting absence of animal ingredients has significantly increased in recent years. The purpose of this study was to document the purchasing behaviour of egg- or milk-allergic consumers vis-à-vis food marketed as "vegan" and "plant-based", and to evaluate the associated allergenic risk. A survey was conducted among egg- and milk-allergic consumers and revealed that 86% (margin of error 5.4%; confidence level 95%) would buy "vegan" products, indicating this label may be perceived as a substitute for "free from milk and eggs". To assess the risk posed by these products, 87 prepackaged foods with "vegan" and/or "plant-based" claims purchased in Quebec were tested for milk proteins, and 64 for egg proteins. Overall, 5.7% and 0% occurrence of milk and egg proteins, respectively, were observed, suggesting that the analysed prepackaged foods carrying "vegan" and/or "plant-based" labels pose little risk to egg- or milk-allergic consumers. However, this is likely due to allergen management practices applied by the Canadian manufacturers of the products tested, and should not be attributed to the use of "vegan" or similar labels. Enhanced regulatory requirements for the use of these labels, and an education campaign on their meaning with respect to allergy-related risks, are necessary to better inform and protect egg- and milk-allergic consumers.

Background: Asthma is a chronic airway inflammatory disease that affects millions of Canadians and often contributes to higher levels of anxiety among patients. Since the coronavirus disease 2019 (COVID-19) pandemic was a time of increased anxiety and fear among the Canadian population, it was thought that those with asthma may experience heightened anxiety levels due to uncertain access to care, the potential to misinterpret asthma symptoms for symptoms of COVID-19 (or vice versa), and the concern about being treated differently by those around them when experiencing asthma symptoms. Therefore, this study sought to perform a cross-sectional analysis of the asthma-anxiety relationship in adults with and without asthma in the unique context of the COVID-19 pandemic from a Canadian perspective.

Methods: This study employed the COVID-19 Associated Anxiety in Allergic Rhinitis and Asthma patients Experiencing Symptoms (CAAARES) survey, consisting of COVID-19-specific questions, the Generalized Anxiety Disorder Assessment-7 (GAD-7) and the Asthma Control Questionnaire-6 (ACQ-6). Data collection occurred through the Qualtrics XM platform and data analyses were conducted with the IBM SPSS Statistics 28 software.

Results: A total of 741 valid responses were collected (asthma group, n = 244; control group, n = 497). 31.6% and 26.2% of respondents in the asthma and control groups, respectively, met the diagnostic criteria for GAD. There was no significant difference (p = .067) in mean GAD-7 scores between the two groups. A Hierarchal Multiple Regression (HMR) model was developed, and neither asthma status nor ACQ-6 score had a significant predictive effect on the GAD-7 score. There was a statistically significant (p < .001) weak positive correlation (r = .22) between GAD-7 and ACQ-6 scores. In a simple mediation (SMM) model, perceived COVID-19 stress of others was not identified as a significant mediator of the relationship between ACQ-6 and GAD-7 (indirect effect β = 0.014).

Conclusion: Our study of a Canadian cohort demonstrates elevated levels of anxiety overall, amongst both asthma and control groups. While AR status was significantly greater in the asthma group, it was not a significant predictive variable of GAD-7 score. Our data suggests that COVID-19-specific factors appear to have a greater contribution to anxiety than asthma status or control.

Background: The rate of cytomegalovirus (CMV) retinitis is increasing, likely secondary to aggressive immunosuppressive regimens for a variety of diseases. Transplant and rheumatological literature show growing evidence suggesting a unique relationship between CMV infection and mycophenolate in particular. This study reports two cases of CMV retinitis infection in patients on mycophenolate immunosuppression.

Case presentation: Case A was a 39-year-old African American woman with systemic lupus erythematosus (SLE) with stage IV lupus nephritis who presented for bilateral retinal detachments with areas of moth-eaten and thin retina concerning for prior viral retinitis. Case B was a 53-year-old man who presented with floaters in the right eye status-post heart transplant since 2008 on immunosuppressive therapy. Fundoscopic examination of the right eye showed frosted branch angiitis with intraretinal hemorrhage and inner retinal thickening and disorganization, consistent with CMV retinitis infection. Both patients were on mycophenolate immunosuppression with the recommendation to reduce or discontinue mycophenolate.

Conclusion: Patients on mycophenolate immunosuppression may be more vulnerable to cytomegalovirus infection, including CMV retinitis. Ophthalmologists should be aware of this increased risk and consider reducing or discontinuing mycophenolate to promote viral clearance in these susceptible patients, in conjunction with the patient's transplant or rheumatology teams.

Background: Real world data on the response to the SARS-CoV-2 vaccine in patients with immunomediated diseases (IMIDs) treated with immunesuppressants is of great interest because vaccine response may be impaired. The main aim was to study the humoral and cellular immune response after SARS-CoV-2 vaccination in patients with IMIDs treated with immunosuppressants. The secondary aim was to describe the frequency of SARS-CoV-2 infections after vaccination in these patients.

Material and methods: This is an observational study including 86 patients with IMIDs. All patients were treated with biologic or targeted synthetic disease-modifying antirheumatic drugs [b/tsDMARDs: TNF inhibitors (TNFi), rituximab, anti-interleukin 6 receptor (anti-IL6R) or JAK inhibitors (JAKi)]. Demographic and clinical information were collected. After 4-6 weeks of 2nd and 3rd vaccine doses, humoral response was assessed using the Thermo Scientific ELiA SARS-CoV-2-Sp1 IgG Test. Also, in patients with serum SARS-CoV-2 antibody levels under 100UI/ml, cellular response was analyzed using the QuantiFERON SARS-CoV-2 Starter Pack.

Results: A total of 86 patients under b/tsDMARDs and 38 healthy controls were included. Most patients received TNFi (45 with TNFi, 31 with rituximab, 5 with anti-IL6R and 5 with JAKi). SARS-CoV-2 antibodies (Ab) were present in an 86% of patients with IMIDs and in 100% healthy controls (p = 0.017). However, 12 (14%) patients had undetectable SARS-CoV-2 Ab levels, all treated with rituximab. In addition, SARS-CoV-2 Ab (IU/ml) were statistically lower in patients (Mdn (IQR): 59.5 (17-163) in patients vs 625 (405-932) in controls, p < 0.001). Patients treated with rituximab had lower Ab levels than those treated with TNFi and controls (p < 0.001). The cellular response to SARS-CoV-2 vaccine was evaluated in 30 patients. Eleven patients had a positive cellular response, being more frequent in patients treated with rituximab (p = 0.03). SARS-CoV-2 infection was reported in 43% of patients and 34% of controls after vaccination. Only 6 (7%) patients required hospitalization, most of whom treated with rituximab (67%).

Conclusion: SARS-CoV-2 antibody levels were lower in patients than in controls, especially in patients treated with rituximab. A cellular response can be detected despite having a poor humoral response. Severe infections in vaccinated patients with IMIDs are rare, and are observed mainly in patients treated with rituximab.

Introduction: Allergy to chicken egg protein is a common form of food allergy. The most common clinical presentation includes gastrointestinal, skin, and respiratory symptoms. Differential diagnosis, including provocative tests, is critical in diagnosis.

Case description: We present a case of a 21-year-old patient with egg allergy, who underwent a double-blind food provocation test with placebo (evaluating subjective complaints from the gastrointestinal tract) and a titrated nasal provocation test using dry chicken egg content. We assessed the response of the nasal mucosa in the provocation test using the visual analogue scale (VAS), acoustic and optical rhinometry, as well as measurements of nitric oxide concentration in the exhaled air. During the provocation test, we measured the changes in the transverse section of the nasal passages, which were accompanied by subjective complaints measured with the VAS scale, using objective techniques. In the nasal provocation test with a dose of 20 µg of chicken egg protein, we observed an increase in the reactivity of the nasal mucosa and a decrease in the level of nitric oxide in the exhaled air from the upper airways (920 ppb before the provocation test and up to 867 ppb during the early stage of the allergic reaction). During the provocation tests, we recorded typical symptoms associated with the early stage of the allergic reaction; including nasal obstruction (1.2 cm), leakage of watery discharge (0.8 cm) in the food test, and itchy nose (1.1 cm) in the food test vs. the nasal test: 4.6, 2.8, and 3.5 cm, respectively.

Conclusions: The nasal mucosa provides convenient conditions for evaluation of the severity of allergy to common food allergens, including chicken egg allergens.

Background: Inborn errors of immunity (IEIs) are considered significant challenges for children with IEIs, their families, and their medical providers. Infections are the most common complication of IEIs and children can acquire coronavirus disease 2019 (COVID-19) even when protective measures are taken.

Objectives: To estimate the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children with IEIs and analyse the demographic parameters, clinical characteristics and treatment outcomes in children with IEIs with COVID-19 illness.

Methods: For this systematic review, we searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guideline for studies on the development of COVID-19 in children with IEIs, published from December 1, 2019 to February 28, 2023, with English language restriction.

Results: Of the 1095 papers that were identified, 116 articles were included in the systematic review (73 case report, 38 cohort 4 case-series and 1 case-control studies). Studies involving 710 children with IEIs with confirmed COVID-19 were analyzed. Among all 710 IEIs pediatric cases who acquired SARS-CoV-2, some children were documented to be admitted to the intensive care unit (ICU) (n = 119, 16.8%), intubated and placed on mechanical ventilation (n = 87, 12.2%), suffered acute respiratory distress syndrome (n = 98, 13.8%) or died (n = 60, 8.4%). Overall, COVID-19 in children with different IEIs patents resulted in no or low severity of disease in more than 76% of all included cases (COVID-19 severity: asymptomatic = 105, mild = 351, or moderate = 88). The majority of children with IEIs received treatment for COVID-19 (n = 579, 81.5%). Multisystem inflammatory syndrome in children (MIS-C) due to COVID-19 in children with IEIs occurred in 103 (14.5%). Fatality in children with IEIs with COVID-19 was reported in any of the included IEIs categories for cellular and humoral immunodeficiencies (n = 19, 18.6%), immune dysregulatory diseases (n = 17, 17.9%), innate immunodeficiencies (n = 5, 10%), bone marrow failure (n = 1, 14.3%), complement deficiencies (n = 1, 9.1%), combined immunodeficiencies with associated or syndromic features (n = 7, 5.5%), phagocytic diseases (n = 3, 5.5%), autoinflammatory diseases (n = 2, 3%) and predominantly antibody deficiencies (n = 5, 2.5%). Mortality was COVID-19-related in a considerable number of children with IEIs (29/60, 48.3%). The highest ICU admission and fatality rates were observed in cases belonging to cellular and humoral immunodeficiencies (26.5% and 18.6%) and immune dysregulatory diseases (35.8% and 17.9%) groups, especially in children infected with SARS-CoV-2 who suffered severe combined immunodeficiency (28.6% and 23.8%), combined immunodeficiency (25% and 15%), familial

Background: Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency caused by mutations in the WAS gene that leads to increased susceptibility to infections, thrombocytopenia, eczema, malignancies, and autoimmunity. Central nervous system (CNS) autoimmune manifestations are uncommon.

Case presentation: We describe the case of a five-year-old boy with refractory thrombocytopenia and iron deficiency anemia who developed relapsing bilateral optic neuritis. Myelin oligodendrocyte glycoprotein antibody (MOG-IgG) via serum fluorescence-activated cell sorting assay was positive (titer 1:100), confirming a diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). At age six, molecular panel testing for genes associated with primary immunodeficiency identified a missense WAS gene variant. He was subsequently found to have decreased WAS protein expression, consistent with a diagnosis of WAS.

Conclusions: This case expands the reported spectrum of CNS autoimmunity associated with WAS and may help to inform long-term therapeutic options.

Background: Aspirin-exacerbated respiratory disease (AERD) and IgG4-related disease (IgG4RD) share a common pathway of Th2-mediated immune mechanism; there have been several cases of IgG4RD developed in patients with asthma, especially in those comorbid with chronic rhinosinusitis (CRS). IgG4RD has often been treated with systemic corticosteroids, rituximab, or immune-suppressive agents, but frequently failed with relapse.

Case presentation: Here, we present a case of a 64-year-old male patient with severe AERD with CRS complicated with IgG4RD, who has been successfully treated and maintained with anti-IL-4 receptor antibody, dupilumab after achieving unsatisfactory responses with previous treatments including steroids, rituximab, omalizumab, and reslizumab. The patient's symptoms (periorbital swelling and asthmatic/nasal symptoms) were remarkably improved; serum levels of IgG4/IgE as well as plasmablast/eosinophil counts progressively decreased without any recurrence sign for over 2 years of dupilumab treatment.

Conclusion: These findings demonstrate that blocking the IL-4/IL-13 pathway with dupilumab can be an effective treatment with long-term safety in patients with severe AERD with CRS complicated by IgG4RD.

Background: Treatment of cystic fibrosis (CF) has been revolutionized by the use of cystic fibrosis transmembrane conductance regulator (CFTR) protein modulators such as elexacaftor/tezacaftor/ivacaftor (ETI) triple therapy. Prior studies support a role for type 2 (T2) inflammation in many people with CF (PwCF) and CF-asthma overlap syndrome (CFAOS) is considered a separate clinical entity. It is unknown whether initiation of ETI therapy impacts T2 inflammation in PwCF. We hypothesized that ETI initiation decreases T2 inflammation in PwCF.

Methods: A single center retrospective chart review was conducted for adult PwCF. As markers of T2 inflammation, absolute eosinophil count (AEC) and total immunoglobulin E (IgE) data were collected longitudinally 12 months prior to ETI therapy initiation and 12 months following therapy initiation. Multivariable analyses adjusted for the age, gender, CFTR mutation, disease severity, inhaled steroid use, and microbiological colonization.

Results: There was a statistically significant reduction (20.10%, p < 0.001) in 12-month mean total IgE following ETI initiation; this change remained statistically significant in the multivariate model. The longitudinal analysis demonstrated no change in AEC following therapy initiation.

Conclusion: This study demonstrates that there is a statistically significant percent reduction in mean total IgE but no change in AEC following ETI initiation. ETI may lead to decreased antigen and superantigen load in the airway as a result of improved mucociliary clearance and these changes may drive the decline in total IgE, without influencing the epigenetic drivers of eosinophilic inflammation. Further studies are warranted to determine the underlying mechanism of ETI impact on T2 inflammation and possible role for asthma immunomodulator therapy post ETI initiation in CFAOS.