International Archives of Allergy and Immunology最新文献

Introduction: The safety of biologics, other than TNF-α inhibitors, during pregnancy has not been sufficiently established. To assess the risk of pregnancy-related adverse outcomes of biologics used for psoriasis, compared to TNF-α inhibitors, we utilized the WHO global pharmacovigilance database (1968-2024).

Methods: We utilized the World Health Organization's global pharmacovigilance database from 1968 to 2024. From over 140 million reports from more than 170 countries, we extracted 6,518 reports of pregnancy-related adverse outcomes associated with the biologics of interest. These biologics included TNF-α inhibitors (e.g., etanercept, infliximab, adalimumab, certolizumab pegol), IL-12/IL-23 inhibitor (e.g., ustekinumab), IL-17 inhibitors (e.g., secukinumab, brodalumab, ixekizumab, bimekizumab), and IL-23 inhibitors (e.g., guselkumab, tildrakizumab, risankizumab). Each biologic was compared to TNF-α inhibitors and certolizumab pegol in two separate disproportionality analyses. The reporting odds ratio (ROR) was calculated for maternal, fetal, and neonatal outcomes, categorized into seven major groups. Multivariable and sensitivity analyses were conducted to validate the primary results.

Results: The disproportionality analysis showed that, compared to TNF-α inhibitors, most biologics had a lower frequency of pregnancy-related adverse outcomes, with the exception of brodalumab. Specifically, ROR and 95% confidence intervals (CIs) were as follows: ustekinumab (ROR, 0.27; 95% CI: 0.21-0.35), secukinumab (0.17; 0.13-0.22), brodalumab (0.20; 0.02-2.21), ixekizumab (0.05; 0.03-0.08), bimekizumab (0.10; 0.01-0.71), guselkumab (0.09; 0.05-0.15), tildrakizumab (0.02; 0.00-0.14), and risankizumab (0.38; 0.25-0.58). However, risankizumab was reported with a higher frequency of abortion and stillbirth (1.87; 1.32-2.63). These findings were consistent when compared to certolizumab pegol, as well as in multivariable and sensitivity analyses. Furthermore, when comparing other TNF-α inhibitors to certolizumab pegol, infliximab showed a lower frequency of pregnancy-related adverse outcomes (ROR, 0.71; 95% CI: 0.55-0.92), etanercept showed a comparable frequency (1.00; 0.77-1.31), and adalimumab showed a higher frequency (1.42; 1.11-1.81).

Conclusions: Biologics used for psoriasis, with the exception of brodalumab, exhibit a lower frequency of pregnancy-related adverse outcomes compared to TNF-α inhibitors and certolizumab pegol, suggesting their potential to be safe options during pregnancy. However, further studies are necessary to evaluate the safety of these biologics during pregnancy, accounting for confounding factors.

Introduction: The meticulous management of risk factors is paramount in the effective control of allergic rhinitis (AR), playing a significant role in diminishing both the direct medical expenditures and the indirect economic impacts associated with the condition. Presently, there is a notable deficiency in research concerning the risk factors for severe AR, as well as the correlation between serum allergen-specific immunoglobulin E (sIgE) levels and the severity of AR symptoms.

Methods: The study utilized data from a cross-sectional epidemiological survey conducted in Guangzhou, China, from April 2023 to March 2024, involved 638 AR patients. We used Visual Analogue Scale (VAS) scores to assess the severity of AR. Data of daily risk factors were collected through face-to-face questionnaires, and serum sIgE levels were measured using the AllergyScreen assay (Mediwiss Analytic GmbH, Moers, Germany). A generalized linear model was used to investigate the associations.

Results: Our findings indicate that patients with severe AR exhibited more unhealthy lifestyle habits and lived in high-risk environments compared to non-severe patients. Physical activity more than three times per week was associated with a reduced risk of severe symptoms (OR: 0.55, 95% CI: 0.36, 0.82). Frequent indoor cleaning also lowered the risk of severe AR (OR: 0.70, 95% CI: 0.56, 0.87). Additionally, a one-level increase in serum sIgE was linked to higher odds of severe AR (OR: 1.26, 95% CI: 1.11, 1.43) after adjusting for risk factors.

Conclusion: Severe AR is associated with poor household cleaning and less exercise. Higher serum sIgE levels correspond to a higher risk of severe AR.

Introduction: Previous studies have suggested an association between vaccines and autoimmune diseases, but they were limited by their narrow focus and timeframe.

Methods: This study conducted the first large-scale international analysis to investigate the impact of various vaccines on autoimmune liver diseases. Utilizing WHO's VigiBase data from 1968 to 2024, and the study identified 1,083 (0.012%) cases of vaccine-associated hepatic autoimmune disorders out of 8,562,584 reported vaccine adverse events.

Results: The vaccines with the highest risk of hepatic autoimmune disorders were the hepatitis B vaccine (reporting odds ratio [ROR], 3.52; 95% CI, 2.50-4.95), COVID-19 mRNA vaccines (ROR, 2.95; 95% CI, 2.73-3.18), and papillomavirus vaccines (ROR, 2.13; 95% CI, 1.45-3.13). Additionally, when vaccine-associated hepatic autoimmune disorders occurred, hepatobiliary adverse events were frequently observed to occur concurrently.

Conclusions: This study suggests that vaccines may induce hepatic autoimmune disorders and highlights the need for enhanced monitoring before and after vaccination. Additionally, it proposes implementing pre-vaccination screening protocols and postvaccination monitoring to address this concern.

Introduction: The objective of this study was to ascertain the predictive value of osteopontin (OPN), a cytokine with pro-inflammatory properties implicated in inflammatory and allergic conditions, in nasal secretions for the identification of chronic rhinosinusitis with nasal polyp (CRSwNP) endotypes and the assessment of disease severity.

Methods: A cohort comprising 81 individuals diagnosed with CRSwNP was enrolled, which included 37 subjects with the non-eosinophilic CRSwNP and 44 subjects with the eosinophilic CRSwNP (eCRSwNP), alongside 32 healthy controls (HCs). Nasal secretions and tissue samples were collected from all participants. The quantification of OPN in these samples was conducted using ELISA and immunohistochemistry. Nasal fractional exhaled nitric oxide levels were determined with the Nano Coulomb Breath Analyzer. The diagnostic efficacy of OPN levels in distinguishing eCRSwNP was assessed using the receiver operating characteristic (ROC) curve, while Pearson correlation analysis was employed to evaluate the correlation between OPN levels and disease severity indicators.

Results: Concentrations of OPN in nasal secretions were found to be elevated in CRSwNP patients compared to the HC group and significantly higher in patients with eCRSwNP. A positive correlation was identified between OPN levels in nasal secretions and peripheral blood eosinophil counts and percentages, and tissue eosinophil counts, as well as the Visual Analog Scale (VAS) score, Lund-Mackay score, and Lund-Kennedy score. The ROC analysis demonstrated that the OPN level in nasal secretions possesses a robust discriminatory capacity for eCRSwNP, with a cutoff value of 121.05 ng/mL. Furthermore, the OPN concentration was determined to be a more precise predictor of the VAS score, Lund-Mackay score, and Lund-Kennedy score than the CRSwNP endotypes.

Conclusion: The findings of this study indicate that OPN is differentially expressed in the nasal secretions of eCRSwNP patients and correlates with eosinophilic inflammation. The presence of OPN in nasal secretions emerges as a novel and potentially valuable biomarker for the differentiation of CRSwNP endotypes and the prognostication of disease severity.

Introduction: Systemic hypersensitivity to hymenoptera species venom is the most common cause for anaphylaxis in adults. Due to similarities between hornet (Vespa crabro) and wasp (Vespula spp.) venom, patients with hornet venom anaphylaxis are often treated similarly to wasp-allergic patients. However, comparative data are scarce. This study aimed to analyze differences and similarities between these two groups.

Methods: A retrospective analysis with 42 patients with certain anaphylaxis to hornet venom was conducted. These were matched for age, gender, and CAP class with 42 patients with wasp venom anaphylaxis. Clinical outcomes and treatment adherence were compared.

Results: Patients with hornet venom anaphylaxis showed a significantly higher degree of anaphylaxis (21 vs. 9 patients with grade III/IV anaphylaxis, p < 0.001), despite similar tryptase levels (6.3 ± 8.3 vs. 5.1 ± 4.2) or presence of mastocytosis (2 vs. 3). These patients also showed significantly lower therapy adherence, resulting in fewer patients undergoing specific immune therapy (29 vs. 37, p = 0.030) or sting challenges (14 vs. 27, p = 0.046). Both groups showed high efficacy of specific immunotherapy with wasp venom extract.

Conclusion: Hornet stings induce more severe anaphylaxis, while patients with hornet venom allergies demonstrate lower treatment compliance, likely due to inadequate education. Specific immunotherapy with wasp venom extract remains effective for both.

Background: This review aimed to examine if atopic dermatitis (AD) led to an increased risk of inflammatory bowel disease (IBD) by collating data from longitudinal studies.

Summary: Cohort and case-control studies examining the risk of IBD, Crohn's disease (CD), or ulcerative colitis (UC) due to exposure to AD were included in this review. Articles were searched on PubMed, CENTRAL, Embase, Scopus, and Web of Science electronic repositories up to 2nd October 2024. Eight retrospective cohort studies with 61,190,816 participants were included. The meta-analysis found that AD was a significant risk factor for IBD (OR: 1.37 95% CI: 1.31, 1.43). No statistical heterogeneity was noted. Pooled analysis showed that exposure to AD was a significant risk factor for both CD (OR: 1.51 95% CI: 1.31, 1.76) and UC (OR: 1.33 95% CI: 1.13, 1.56). Both meta-analyses had high inter-study heterogeneity with I2=83% and I2=89% respectively. Results remained significant on sensitivity analysis.

Key messages: Our study shows an association between AD and IBD. The association was persistent for both CD and UC. Given the small increase in risk of IBD in AD, its clinical relevance may be questionable.

Introduction: House dust mite is the primary trigger of allergic respiratory diseases worldwide, and allergen-specific immunotherapy (AIT) is the only disease-modifying treatment in the clinic. The use of allergen molecules instead of extracts is a promising strategy in AIT. In this study, we constructed a peptide hybrid vaccine against the major mite allergen Der f 35 and verified its hypoallergenicity, making it to be a promising candidate for AIT of mite allergy.

Methods: The gene encoding Der f 35 was retrieved and synthesized. The hypoallergenic peptide fragments derived from the B-cell epitopes were synthesized based on the predicted profiles of B-cell or T helper-cell epitopes in Der f 35, they were verified by immunoglobulin E (IgE)-reaction test and fused to non-allergenic protein carrier to form the hybrid vaccine. Both the wild-type Der f 35 and the designed vaccine were expressed in Escherichia coli and purified by chromatography; their IgE-binding activity was compared by indirect enzyme-linked immunosorbent assay (ELISA), Western blot, inhibition ELISA, and basophil activation test (BAT). The blocking immunoglobulin G (IgG) against the designed vaccine was raised in rabbits and its ability to inhibit IgE binding of Der f 35 was evaluated by ELISA. The vaccine's effects on peripheral blood mononuclear cells (PBMCs) were investigated.

Results: A total of 29 out of 60 (48.33%) IgE-positive sera against Der f 35 were screened. Five peptide fragments (residue 39-42, 60-67, 73-107, 111-118, 126-143) from Der f 35 were selected as candidates, in which four peptides exhibited almost no IgE reactivity and the fragment 73-107 had weak reactions. Only 5.98-24.02% inhibition rates could be achieved by the peptides when compared with Der f 35 (97.32%). The designed vaccine migrated at approximately 30 kDa by SDS-PAGE. The IgE-ELISA revealed a significant reduction in IgE-binding activity to the vaccine when compared to wild-type Der f 35 (p < 0.0001); the decreased allergenicity was further confirmed by IgE-Western blot, inhibition ELISA, and BAT, respectively. The IgE-reactivity of Der f 35 could be blocked by the vaccine-induced IgG (p < 0.01). The levels of IL-5 and IL-13 from PBMCs were significantly decreased after stimulation by the vaccine than that by Der f 35 (p < 0.05).

Conclusion: The designed B-cell epitope vaccine of Der f 35 showed greatly diminished allergenicity and Th2 activity. It could be an effective and safe candidate to prevent allergic adverse reactions during the immunotherapy of mite allergy and merits the further study.

Introduction: The aim of this study was to investigate the effects of the compound Lactobacillus acidophilus in combination with montmorillonite powder on the inflammatory response in children with rotavirus enteritis (RVE).

Methods: A total of 94 children with RVE admitted to our hospital between June 2021 and April 2023 were selected and divided into two groups using a random digit table method. Each group consisted of 47 children. Both groups were administered standard symptomatic treatment upon admission. The control group was additionally administered montmorillonite powder, while the observation group was administered compound L. acidophilus tablets in addition to the treatment administered to the control group. Both the treatments were administered for a duration of 5 days. Parameters such as clinical efficacy, symptom relief time (diarrhea, vomiting, fever, dehydration), inflammatory response (C-reactive protein [CRP]), and adverse reactions (constipation, bloating, drowsiness, skin allergy, dry mouth) were compared between the two groups.

Results: Posttreatment, the observation group exhibited a significantly higher total effective rate (95.74%) compared to the control group (78.72%). The symptom relief time for diarrhea ([2.23 ± 0.48] days), vomiting ([1.38 ± 0.25] days), fever ((1.91 ± 0.68) days), and dehydration ([2.74 ± 0.53] days) in the observation group were all significantly shorter than those in the control group ([3.42 ± 0.71] days, [2.65 ± 0.54] days, [2.76 ± 0.84] days, and [4.60 ± 0.89] days), respectively. The posttreatment CRP levels in the observation group were (5.26 ± 1.32) mg/L, lower than those in the control group (7.45 ± 1.58) mg/L, although this difference was not statistically significant. The incidence of adverse reactions was 14.89% in the observation group and 8.51% in the control group, with no significant difference between the groups.

Conclusion: The combination of compound L. acidophilus and montmorillonite effectively shortens the symptom recovery time and improves inflammatory response in children with RVE, while maintaining a high safety profile.

Introduction: Previous studies have indicated asthma, allergic rhinitis (AR), and chronic rhinosinusitis (CRS) may influence brain structure. However, it remains unclear whether these three airway conditions cause brain structural changes and which specific brain regions are affected.

Methods: We conducted a Mendelian randomization (MR) to explore the causal effect of AR, CRS, and asthma on brain structure. Reverse MR was conducted to investigate potential impact of changes in brain structure on AR, CRS, and asthma. Additionally, to enhance our understanding of the lung-brain axis, we examined bidirectional relationships between Alzheimer's disease, Parkinson's disease, insomnia, major depression, neuroticism, attention deficit hyperactivity disorder, and these three respiratory disorders.

Results: The genetically predicted CRS could reduce the surface area in the banks of the superior temporal sulcus, paracentral, and superior frontal. Asthma had an association with a decrease in the surface area of the entorhinal, fusiform, and temporal pole, as well as a reduction in the volume of amygdala. Asthma could also increase the thickness of pericalcarine. Reverse MR showed that changes in the surface area of pars opercularis and thickness of entorhinal cortex had a potential effect on CRS. Besides, bidirectional MR between 3 airway disorders and 6 neuropsychiatric disorders indicated neuroticism could raise risk for asthma, and major depression could increase the risk of CRS and asthma.

Conclusion: Our MR analysis revealed a potential causal relationship among CRS, asthma, and atrophy in specific functional areas of the human brain, supporting the existence of a lung-brain axis.

Introduction: ABAT, a key enzyme in GABA catabolism, modulates antitumor immune activity across various cancers. However, the molecular mechanisms by which the ABAT/GABA axis exerts immune regulation in the liver cancer microenvironment remain unclear.

Methods: ABAT expression in liver cancer tissues was scrutinized via the TCGA-LIHC database, and the 5-year survival rates of liver cancer patients were appraised through Kaplan-Meier survival analyses. The mRNA levels of ABAT in liver cancer cell lines were quantified by qRT-PCR. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), colony formation, and Transwell assays were employed to gauge the influence of ABAT overexpression on liver cancer cell growth, proliferation, migration, and invasion, respectively. Western blot evaluated epithelial-mesenchymal transition-related protein expression. ELISA quantified GABA, IL-10, TGF-β1, Granzyme B, and IFN-γ in the culture medium. Flow cytometry was used to measure the frequency of CD25+FOXP3+ cells and the expression of CD25, CD69, and PD-1 on CD8+T cells in coculture. Carboxifluorescein diacetate succinimidyl ester dilution assays were performed to assess the proliferative activity of CD8+T cells.

Results: ABAT was found to be underexpressed in liver cancer tissues and cells, and such underexpression is indicative of a poorer prognosis for patients, while its overexpression was shown to curb the malignancy of liver cancer cells. Upon overexpression of ABAT, there is a decrease in GABA levels in the cell supernatant, coupled with an increase in IL-10 and TGF-β1 cell number, and an upsurge in the CD25+FOXP3+ cell ratios, all of which were restored by the addition of exogenous GABA. Furthermore, the depletion of ABAT led to a reduction in the proliferation and tumor-killing ability of CD8+T cells, effects that were reversed by the application of GABAA receptor inhibitors.

Conclusion: ABAT functions to inhibit Treg differentiation in liver cancer through downregulation of GABA, thus promoting the antitumor activity of CD8+T cells.