Lower IgA Levels in Chronic Spontaneous Urticaria Are Associated With Lower IgE Levels and Autoimmunity.
Ontology highlight
ABSTRACT: Background
The pathogenesis of chronic spontaneous urticaria (CSU) is still insufficiently understood. Recent findings suggest that immunoglobulins, in particular IgE but also IgA, play a role in the development of CSU.Objective
Our aim was to assess differences in clinical and laboratory markers between CSU patients with and without lower levels of serum IgA and IgE.Methods
We analyzed the data of 606 patients with CSU by dividing them into four groups based on their IgA and IgE levels. The groups were compared for their spectrum of symptoms, disease activity, concomitant autoimmunity and routine laboratory markers. Autoreactivity was assessed by basophil activation test (BAT). Moreover, IgE-anti-thyroid peroxidase (TPO) was measured.Results
Of the patients with lower IgE levels, 66.5% also had lower IgA levels (r=0.316, p<0.001). Patients with lower IgA and lower IgE levels showed a higher prevalence of recurrent angioedema (p=0.03, p=0.04) and concomitant autoimmunity (p=0.006, p<0.001). Autoreactivity was also found more frequently in patients with lower IgA and lower IgE levels (p=0.003, p<0.001). Reduced basophil counts were linked to both, lower IgA and lower IgE levels (p<0.001), whereas low eosinophil counts were primarily present in patients with lower IgE levels (p=0.04, p<0.001). Patients with elevated IgE-anti-TPO levels had lower IgA (p=0.007) and IgE levels (p=0.001).Conclusion
Lower IgA levels in CSU are linked to lower IgE levels and features of autoimmune urticaria. Our findings encourage to screen CSU patients for serum IgA and IgE levels and to further assess their role as disease biomarkers.
SUBMITTER: Sauer M
PROVIDER: S-EPMC8128143 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundIgE bound on the surface of mast cells contributes to the pathogenesis of chronic spontaneous urticaria (CSU). Atopy is a predisposing factor for CSU, where omalizumab is a widely used monoclonal antibody to control urticaria symptoms via capturing serum free IgE. However, the role of serum free IgE is not clarified in CSU. The present study evaluated the clinical relevance of serum free IgE in patients with CSU.MethodsEighty-eight patients with CSU and 76 healthy controls (HCs) were enrolled in this study. Serum total and Dermatophagoides pteronyssinus (Der p)-specific IgE levels were measured by ImmunoCAPs. The serum free IgE levels were measured by ELISA using a novel IgETRAP, and their associations with clinical parameters, including urticaria activity score (UAS), were evaluated. Changes in serum free and total IgE levels after omalizumab treatment were observed in 23 CSU patients in comparison between responders (≥50% reduction in UAS) and non-responders (<50% reduction).ResultsSignificantly higher serum free/total IgE levels were noted in CSU patients than in HCs with a positive correlation between the 2 values (rho = 0.87, P < 0.001). Among CSU patients, atopics had significantly higher serum free IgE levels than non-atopics, while no associations were noted with UAS, urticaria duration, or the results of serum ANA or autologous serum skin tests. In addition, there were no significant changes in serum free IgE levels during 12 months of omalizumab treatment. No significant differences were noted in serum free/total IgE levels or clinical parameters between responders and non-responders, while responders have higher serum Der p-specific IgE level and its ratio to serum free/total IgE level than non-responders (P < 0.05, respectively).ConclusionsThese findings suggest that increased serum free IgE may be involved in the development of CSU by activating mast cells, especially in atopics. High Der p-specific IgE level and its ratio to serum free IgE level may be a potential biomarker for predicting favorable responses to omalizumab in CSU.
| S-EPMC8883342 | biostudies-literature
Project description:BackgroundChronic spontaneous urticaria (CSU) is a heterogeneous disease with some frequent comorbidities like autoimmune diseases, drug reactions, and inducible urticaria. IgE antibodies against thyroid peroxidase (anti-TPO IgE) could be associated with some of these clinical characteristics.ObjectiveTo explore the clinical characteristics of CSU patients, according to the presence of anti-TPO IgE in serum.MethodsAnti-TPO IgE levels were measured during the clinical control period (Urticaria Activity Score, 0 point) and exacerbation period (≥3 points) in 100 CSU patients. Patients with self-reported exacerbation of skin involvement by foods, nonsteroidal anti-inflammatory drugs (NSAIDs), and physical triggers underwent controlled challenge tests.ResultsWe identified 2 groups of patients: (1) patients with anti-TPO IgE during the clinical control period or during an exacerbation, who had a higher frequency of atopy, asthma, and positive challenge test results with NSAIDs and (2) patients without anti-TPO IgE during any period, who had a higher frequency of positive challenge test results for inducible urticaria. Among the first group (anti-TPO IgE at any point), we identified 3 subgroups: patients with anti-TPO IgE during the clinical control period (n = 12); patients with anti-TPO IgE during the clinical control period and significantly increased levels during an urticaria exacerbation (n = 18); and patients with anti-TPO IgE only during an exacerbation (n = 13). None of the patients with self-reported food reactions had a positive challenge test result.ConclusionAnti-TPO IgE is a useful biomarker for differentiating between clinical phenotypes of patients with CSU. Elevation of anti-TPO IgE during exacerbation periods supports an association between this autoantibody and the pathogenesis of urticaria.
| S-EPMC6925798 | biostudies-literature
Project description:ObjectiveImmunoglobulin E (IgE) and its receptor, FcɛRI, importantly contribute to the pathophysiology of chronic spontaneous urticaria (CSU). Recent findings point to a possible role of total IgE as a marker of CSU disease activity, endotypes, and responses to treatment. The evidence in support of total IgE included in the diagnostic workup of patients with CSU has not yet been reviewed.MethodsPublications were searched via PubMed. The search terms used were "chronic urticaria" and "total IgE." Studies were screened by titles and abstracts, and 141 were used in the review.ResultsCSU patients frequently had elevated total IgE serum levels (up to 50%), but normal or very low total IgE levels also occurred. High total IgE may represent high disease activity, longer disease duration, high chance of responding to omalizumab treatment, quick relapse after stopping omalizumab, and lower chance of responding to cyclosporine. Low IgE, in contrast, may suggest Type IIb autoimmune CSU, poor response to treatment with omalizumab and a better chance to benefits from cyclosporine treatment. Furthermore, IgE in different CSU cohorts may have different physicochemical properties that could explain differences in treatment responses to IgE-directed therapies.ConclusionThe results of our review suggest that total IgE is a valuable marker for CSU, and we recommend its assessment in the routine diagnostic workup of CSU patients.
| S-EPMC7840871 | biostudies-literature
Project description:BackgroundChronic spontaneous urticaria (csU), which is characterized by recurrent episodes of mast cell-driven wheal and flare-type skin reactions, is often associated with elevated total IgE levels and thyroid autoimmunity. We speculate that some csU patients express IgE autoantibodies against thyroid antigens such as thyroid peroxidase (TPO), which could bind to skin mast cells and induce their activation.MethodsWe developed and used a site-directed human IgE capture ELISA to quantify IgE-anti-TPO. We used this assay and investigated csU patients (n?=?478) and healthy control subjects (n?=?127) for IgE-anti-TPO and then assessed IgE-anti-TPO-positive and -negative csU patients for clinical and serological differences.Principal findingsCsU patients were found to express more than 2fold higher IgE-anti-TPO serum levels as compared to healthy control subjects (p<0.001). 54% of csU patients had serum levels higher than the cut off (?=?5 IU/ml). By distribution analyses we identified two distinct subpopulations of csU patients: 1) IgE-anti-TPO(low) (?=?39%, IgE-anti-TPO: median 2.17 interquartile range 0.86-5.44, ?=? comparable to healthy controls) and 2) IgE-anti-TPO(high) (?=?61%, IgE-anti-TPO: median 6.67, interquartile range 5.39-8.24). IgE-anti-TPO-positive and -negative csU patients had very similar distributions of age and gender as well as disease activity and duration. IgE-anti-TPO-positive csU patients exhibited significantly higher IgG-anti-TPO levels and lymphocyte counts as well as decreased C4 complement levels.ConclusionOur findings show that a sizeable subgroup of csU patients expresses IgE antibodies against thyroid peroxidase. These autoantibodies could cause "autoallergic" mast cell activation, a novel pathomechanism of chronic spontaneous urticaria.
| S-EPMC3075251 | biostudies-literature
Project description:Urticaria and angioedema are very common. Management of chronic urticaria subtypes, which usually persist for many years, is challenging. Recent years have demonstrated that targeting IgE with antibodies provides a safe and efficient treatment approach. Whilst several anti-IgE antibodies have been developed, omalizumab is currently the only one approved for use. International and national guidelines recommend its use after failure of antihistamines at standard and increased dose. Whilst not yet approved, many new anti-IgE approaches are currently being investigated in pre-clinical studies or clinical trials. This non-systematic focused review summarizes current knowledge of omalizumab and other anti-IgE biologics in chronic urticaria using data extracted from PubMed, Google Scholar and clinical trial databases, clinicaltrials.gov and clinicaltrials.eu. For adults, there is good evidence from randomized clinical trials and real-world data that symptomatic treatment with omalizumab is efficacious and safe in chronic spontaneous urticaria (CSU), whereas evidence in chronic inducible urticaria (CINDU) and special populations is limited. Easy-to-use tools to identify non-responders and predict the required duration of treatment have not been established yet. Phase 2 b results of ligelizumab have not only demonstrated efficacy and safety but also superiority to omalizumab. Indeed, there is preliminary evidence that omalizumab non- or partial responders benefit from ligelizumab. Whereas further development of quilizumab was discontinued, other approaches, eg UB-221 or DARPins are under investigation. Anti-IgE treatment with omalizumab represents a landmark in the treatment of chronic urticaria, with and without angioedema, and there is light on the horizon suggesting success may come with various next-generation anti-IgE approaches.
| S-EPMC7898214 | biostudies-literature
Project description:Immunoglobulin (Ig) E and IgG anti-thyroid autoantibodies (AAbs) play important roles in the immunopathogenesis of chronic spontaneous urticaria (CSU). To date, association of IgE and IgG AAbs with Chinese CSU patients has not been fully investigated. We aimed to explore prevalence rates of IgE and IgG AAbs in Chinese CSU patients and their association with clinical and laboratory parameters. Serum IgE and IgG AAbs against thyroid peroxidase (TPO) and thyroglobulin (TG), total IgE (tIgE) and specific IgEs were measured using enzyme-linked immunosorbent assay, chemiluminescence microparticle immunoassay and immunoblotting. Meta-analyses and literature review were conducted. The meta-analyses indicated that CSU cases were 4.98, 6.90 and 6.68 times more likely to have positive anti-TPO IgE, anti-TPO IgG and anti-TG IgG (all P < 0.001) compared with controls, respectively, and revealed a positive correlation between the prevalence rates of anti-TPO IgE and anti-TPO IgG (r = 0.53, P = 0.025). A total of 1,100 Chinese Han adult CSU patients and 1,100 ethnicity-, age- and sex-matched healthy controls were recruited from 15 centers. Prevalence rates of anti-TPO IgE, anti-TPO IgG, anti-TG IgE or anti-TG IgG in the patients were all significantly higher than those in the controls. Significant correlations were observed between prevalence rates of anti-TPO IgE and anti-TPO IgG (r = 0.297, P < 0.001) as well as between those of anti-TG IgE and anti-TG IgG in the patients (r = 0.137, P < 0.001). Patients with anti-TPO IgE or anti-TPO IgG had significantly lower tIgE levels (P < 0.001). Positive anti-TPO IgE, positive anti-TPO IgG and tIgE < 40 IU/mL were independent predictors of antihistamine-refractory cases. In conclusion, the prevalence rates of IgE and IgG AAbs in Chinese CSU patients are significantly elevated and reciprocally correlated. This study verifies the results of previous case-control studies of CSU patients from other populations and ethnicities.
| S-EPMC8724827 | biostudies-literature
Project description:Chronic spontaneous urticaria (CSU) is characterized by typically short-lived and fleeting wheals, angioedema or both, which occur spontaneously and persist for longer than 6 weeks. This term is applied to the most common subtype of chronic urticaria. The underlying pathophysiology for CSU involves mast cell and basophil degranulation with release of histamine, leukotrienes, prostaglandins and other inflammatory mediators. Although a variety of treatments exist, many patients do not tolerate or benefit from the existing therapies and even require more effective treatments. Omalizumab is currently the only licensed biologic for antihistamine-refractory CSU, and novel drugs are under development. This article reviews its current status regarding pathogenesis and approach to treatment as well as therapeutic agents that are under development for the treatment of CSU.
| S-EPMC6557779 | biostudies-literature
Project description:Introduction Chronic inducible urticaria (CIndU) is a subgroup of chronic urticaria induced by a specific stimulus. We evaluated basophil characteristics in patients with CIndU and compared with those in patients with chronic spontaneous urticaria (CSU) and healthy controls (HCs). Methods Blood was collected from patients, and a basophil activation test (BAT) was performed. Basophil responsiveness and surface marker expression in patients with CIndU were compared with those in patients with CSU and HCs. For some patients with CIndU, blood was collected before and after wheals were induced. In these cases, we compared the responsiveness of basophils before and after the appearance of wheals. Result HCs (n=23) and patients with CIndU (n=24) or CSU (n=38) were enrolled in the study. The degree of basophil activation at steady state in patients with CIndU was higher than in HCs. Basophil responsiveness via high-affinity IgE receptor (FcϵRI) stimulation with anti-IgE or anti-FcϵRI antibody in patients with CIndU was equivalent to that in HCs, and higher than that in patients with CSU. No abnormalities in IgE and FcϵRI expressions on the surface of basophils in patients with CIndU were observed. When we induced wheals in some patients with CIndU and performed a BAT before and after the appearance of wheals, no significant changes were found. Conclusion Peripheral blood basophils in CIndU were slightly activated at steady state, but no abnormalities in basophil responsiveness. In future, a higher number of cases should be enrolled to confirm the role of basophils and refine therapeutic targets for CIndU.
| S-EPMC9539802 | biostudies-literature
Project description:PurposeEosinophils are frequently found in atopic dermatitis (AD) and chronic spontaneous urticaria (CSU) that release eosinophil peroxidase (EPX) and eosinophil cationic protein (ECP). Continuous exposure to these proteins could trigger an autoimmune response which may contribute to the pathogenesis and severity of skin inflammation. In this study, we investigate the immunoglobulin E (IgE) response against eosinophil proteins in CSU and AD.MethodsWe recruited patients with severe AD, severe CSU and healthy subjects to explore the presence of IgE autoantibodies and cross-reactivity against EPX, ECP and thyroid peroxidase (TPO). The potential cross-reactive epitopes among the peroxidase family were determined using in silico tools.ResultsThe frequencies of anti-EPX IgE (28.8%) and anti-ECP IgE (26.6%) were higher in the AD group, and anti-TPO IgE was higher in the CSU group (27.2%). In the CSU group, there was a correlation between the anti-EPX IgE and anti-TPO IgE levels (r = 0.542, P < 0.001); TPO inhibited 42% of IgE binding to EPX, while EPX inhibited 59% of IgE binding to TPO, suggesting a cross-reactivity with EPX as a primary sensitizer. There was greater inhibition when we used a pool of sera CSU and AD, TPO inhibited 52% of IgE binding to EPX, while EPX inhibited 78% of IgE binding to TPO. In silico analysis showed a possible shared epitope in the peroxidase protein family.ConclusionsIgE against eosinophil proteins may contribute to chronic inflammation in patients with AD and CSU. Cross-reactivity between EPX and TPO could explain thyroid problems in CSU patients.
| S-EPMC8419645 | biostudies-literature
Project description:ObjectivesTo obtain utility estimates suitable for use in economic models for chronic spontaneous (idiopathic) urticaria (CSU).MethodsPatient-level data from three randomized clinical trials-ASTERIA I, ASTERIA II and GLACIAL-were analysed. Health states were derived from the Urticaria Activity Score over 7 days (UAS7); higher scores denote greater activity. The health state score ranges were urticaria free: 0; well-controlled urticaria: 1-6; mild urticaria: 7-15; moderate urticaria: 16-27; and severe urticaria: 28-42. The mean EQ-5D utilities were calculated for each health state. A mixed model was used to predict the EQ-5D according to UAS7 health states in a pooled data set containing all treatment arms and time points from the three trials. Pooled trial data were validated through visual comparisons and interaction terms. Fixed and random effects for trials and patients were included, along with the following covariates: UAS7 health state at baseline (moderate or severe); presence of angioedema at baseline and during follow-up; duration of CSU; number of previous CSU medications; visit; current treatment; and patient age and sex.ResultsThere was a consistent improvement in EQ-5D utilities as urticaria activity decreased. The mean utilities ranged from 0.710 (severe urticaria) to 0.780 (moderate urticaria), 0.829 (mild urticaria), 0.862 (well-controlled urticaria) and 0.894 (urticaria free). Sensitivity and subgroup analyses confirmed the robustness of the results.ConclusionThe results suggest that EQ-5D utility scores increase with decreasing urticaria activity. EQ-5D utility scores enable the health-related quality of life of CSU patients to be compared with that of patients with other diseases.
| S-EPMC4828466 | biostudies-literature