Investigating Novel Food Sensitization: A Real-Life Prevalence Study of Cricket, Locust, and Mealworm IgE-Reactivity in Naïve allergic Individuals.

BACKGROUND AND OBJECTIVE: With the global population on the rise, edible insects are considered a potential solution to food security, although concerns about risks such as anaphylaxis exist. METHODS: 2,014 participants underwent testing with the Allergy Explorer-ALEX-2 including extracts of three novel foods: Acheta Domesticus (Ad), Locusta migratoria (Lm), and Tenebrio molitor (Tm). The IgE-mediated sensitization status was investigated in participants who had never knowingly consumed these insects. Data was recorded using an electronic database. RESULTS: 195 individuals (9.7% of all participants) were sensitized to insects. Tropomyosin was co-recognized by 34%, and 18.5% were positive for arginine kinases. Reactivity to Sarcoplasmic-CB, Troponin-C, Paramyosin, or Myosin-light-chain was found in less than 5% of the population, whereas 108 individuals (55.4%) did not show any reactivity to invertebrate panallergens. Additionally, 33 individuals (16.9%) exhibited monosensitization exclusively to insects. Multivariate analysis revealed an inverse association between arachnid reactivity and sensitization to insect allergens, while Mollusca, Blattoidea, and tropomyosin reactivity displayed a direct relationship. Furthermore, Myosin-light-chain reactivity correlated with Ad and Lm, and Troponin-C with Ad and Tm sensitization. CONCLUSION: Edible insect extract IgE sensitization was observed in individuals without prior exposure to such foods. Mites showed a low likelihood of being primary sensitizers due to their inverse association with insect reactivity. Conversely, the direct association of insect sensitization with mollusk and cockroach extract reactivity suggests their potential as primary sensitizers in these participants. Tropomyosin consistently exhibited a positive association with reactivity to all studied insects, supporting its role as a primary sensitizer.

Food-dependent exercise-induced allergic reactions in Lipid Transfer Protein (LTP) hypersensitive subjects: new data and a critical reappraisal.

Summary: Background. Lipid transfer protein is the main cause of both primary food allergy and food-dependent exercise-induced allergic reactions (FDEIAR) in Italy. What characterizes LTP-hypersensitive patients with FDEIAR is still unclear. We investigated the key characteristics of LTP-hypersensitive patients with or without FDEIAR in a large cohort of individuals sensitized to this allergen. Methods. 1,203 food-allergic patients, diagnosed on the basis of unequivocal clinical history and presence of circulating food allergen-specific IgE were studied. Serum IgE reactivity was assessed using the Allergen ExplorerALEX® system (Macroarray Diagnostics, Vienna, Austria). Association of specific IgE reactivities with FDEIAR was investigated, and patients with and without FDEIAR sensitized to LTP were compared. Results. 116 subjects (9.6%) had FDEIAR. Among these, 77 (66.3%) were LTP-reactors and 16 (13.8%) were sensitized to Tri a 19 (omega-5-gliadin). Different LTPs and omega-5-gliadin emerged as the sole allergens clearly associated with FDEIAR. Severity of allergic reactions was paralleled the level of specific IgE to LTPs. Patients with FDEIAR showed significantly lower IgE levels than their counterparts with food allergy at rest, and displayed nearly identical IgE levels regardless of the severity of allergic reactions induced by exercise. Conclusions. FDEIAR are associated with specific allergens. Specific IgE levels in LTP-hypersensitive patients with FDEIAR show an intermediate titer between those simply sensitized and those showing classic food allergy.

The autologous serum skin test (ASST) predicts the response to anti-IgE treatment in Chronic Spontaneous Urticaria patients: a prospective study.

Summary: Background. Chronic spontaneous urticaria (CSU), characterized by recurrent itchy wheals and angioedema for > 6 weeks, is a quite common disease that may heavily impair the quality of life. Omalizumab, an anti-IgE mAb, has much improved the management of CSU but patients' response to the drug may vary and predictive markers are still largely missing. We investigated the predictive value of the autologous serum skin test (ASST) on omalizumab response. Methods. 15 patients with severe CSU eligible for omalizumab treatment were prospectively studied submitting them to ASST and to complete blood count, D-dimer, anti-thyroid peroxidase antibodies, and total IgE measurement before the start of the treatment. Results. 14/15 (93%) responded brilliantly to omalizumab at 3 months assessment. 7 responded in less than 1 month ("early responders") and 7 only after multiple administrations ("late responders"). Of 9 patients scoring positive on ASST, 7 (78%) were late, and 2 (22%) early responders to omalizumab (p = 0.021). Of 6 patients scoring negative on ASST, 5 were early omalizumab responders and 1 did not respond. The PPV and NPV of the ASST for a "late" response to omalizumab were 78% and 100%, respectively. Total IgE were significantly higher in early responders. Conclusions. Although larger prospective studies are needed to confirm these results, this study confirms previous retrospective investigations that the positive ASST appears to predict a slow response to omalizumab in CSU patients.

A European-Japanese study on peach allergy: IgE to Pru p 7 associates with severity.

BACKGROUND: Pru p 3 and Pru p 7 have been implicated as risk factors for severe peach allergy. This study aimed to establish sensitization patterns to five peach components across Europe and in Japan, to explore their relation to pollen and foods and to predict symptom severity. METHODS: In twelve European (EuroPrevall project) and one Japanese outpatient clinic, a standardized clinical evaluation was conducted in 1231 patients who reported symptoms to peach and/or were sensitized to peach. Specific IgE against Pru p 1, 2, 3, 4 and 7 and against Cup s 7 was measured in 474 of them. Univariable and multivariable Lasso regression was applied to identify combinations of parameters predicting severity. RESULTS: Sensitization to Pru p 3 dominated in Southern Europe but was also quite common in Northern and Central Europe. Sensitization to Pru p 7 was low and variable in the European centers but very dominant in Japan. Severity could be predicted by a model combining age of onset of peach allergy, probable mugwort, Parietaria pollen and latex allergy, and sensitization to Japanese cedar pollen, Pru p 4 and Pru p 7 which resulted in an AUC of 0.73 (95% CI 0.73-0.74). Pru p 3 tended to be a risk factor in South Europe only. CONCLUSIONS: Pru p 7 was confirmed as a significant risk factor for severe peach allergy in Europe and Japan. Combining outcomes from clinical and demographic background with serology resulted in a model that could better predict severity than CRD alone.

Chronic spontaneous urticaria: from the hunt for causes and pathogenesis to the identification of different endotypes.

Summary: The hunt for the causes and pathogenic mechanisms involved in chronic spontaneous urticaria (CSU) has engaged clinicians and scientists for decades. Although not all aspects of the disease are defined, our knowledge has now improved to the point that we can consider CSU as an umbrella clinical phenotype under which several different endotypes probably exist. The present article will briefly summarize the fascinating history of the progress in our knowledge of this disease.

35 years of autologous serum skin test in chronic spontaneous urticaria: what we know and what we do not know.

Summary: The autologous serum skin test (ASST) has been used in patients with chronic spontaneous urticaria (CSU) as a means to detect an autoreactivity state for thirty-five years now. Nonetheless, several aspects of this old diagnostic test are still insufficiently defined. Particularly, the nature of the factor(s) responsible for the appearance of the wheal-and-flare skin reaction is still poorly characterized. This article will review our current knowledge about the clinical significance of the ASST and the factors possibly associated with the occurrence of the skin reaction following the intradermal administration of autologous serum that are known so far.

IgE-mediated reactivity to non-specific lipid transfer protein (nsLTP): clinical implications and management ‒ consensus document of the Association of Italian Territorial and Hospital Allergists and Immunologists (AAIITO).

Summary: The primary cause of adult-onset food allergy in Mediterranean countries is IgE-mediated reactivity to non-specific Lipid Transfer Protein (nsLTP), with a prevalence of 9.5% in Italy. nsLTP is heat- and pepsin-stable due to its 3D structure, causing severe allergic reactions, even anaphylaxis. It's conserved across plants and a "panallergen" due to homologous forms in various vegetable foods. Found in Rosaceae fruits' skin, it's categorized into nsLTP1 (9 kDa) and nsLTP2 (7 kDa), representing 93% and 7% of the molecules described to date, respectively. Pru p 3 (nsLTP1) from peach is a primary sensitizer, binding more epitopes than other homologs. Cross-reactivity varies in sensitized patients, influenced by IgE levels. Clinical manifestations range from none to various symptoms. Managing patients sensitized to nsLTP without clinical allergy is a challenge. Sensitization hierarchy usually starts with peach, then expands through Prunoideae, Rosaceae, and other foods. Clinical symptoms don't always expand across LTPs. Patients can tolerate some nsLTP-containing foods and consuming them may maintain tolerance. The absence of guidelines led to the Associazione Allergologi Immunologi Italiani Territoriali e Ospedalieri (AAIITO) creating a consensus-based document. Strategies involve avoidance, self-injectable adrenaline, verification through in vivo and in vitro testing, considering cofactors, and peeling fruits. In localized reactions, abstinence is recommended if specific IgE is high. Concurrent pollinosis may complicates diagnosis, but may help management since symptoms are often less severe. Asymptomatic patients are advised to continue normal diets while considering cofactors and total IgE levels. Management strategies should be case-specific, based on expert Consensus Document.

Clinical severity of LTP syndrome is associated with an expanded IgE repertoire, FDEIA, FDHIH, and LTP mono reactivity.

Summary: Background. LTP allergy is often a challenge for clinicians. We evaluated a multiplex diagnostic approach with diverse cofactors to stratify LTP syndrome risk. Methods. Of the 1,831 participants screened with 'Allergy Explorer-ALEX-2', 426 had reactions to at least one LTP. Data was gathered and recorded via an electronic database. Results. Reactivity to peach Pru p 3 was found in 77% of individuals with LTP allergy. Higher levels of specific IgE and concurrent sensitization to more than 5 molecules (50% of all LTP-sensitised participants, 62% of symptomatic cases) were significantly associated with an increased risk of severe reactions (p = 0.001). Several cofactors, either alone or in combination, also influenced patients' clinical outcomes. Some cofactors increased the risk of severe reactions, such as mono reactivity to LTP in 44.6% of cases (p = 0.001), FDEIA in 10.8% of patients (p = 0.001), and FDNIH in 11.5% (p = 0.005). On the other hand, reactivity to PR10 (24.2%; p = 0.001), profilin hypersensitivity (10.3%; p = 0.001), and/or atopic dermatitis (16.7%; p = 0.001) had a mitigating effect on symptom severity. Conclusions. Clinical severity of LTP syndrome is associated with an expanded IgE repertoire in terms of the number of LTP components recognized and increased IgE levels in individual molecules. Ara h 9, Cor a 8, and Mal d 3 showed the strongest association with clinical severity. In addition, several cofactors may either exacerbate (FDEIA, FDHIH, and LTP monoreactivity) or ameliorate (atopic dermatitis and co-sensitization to profilin and/or PR10) individual patient outcomes. These factors may be utilized for the daily clinical management of LTP syndrome.

Clinical variables of severe chronic spontaneous urticaria from total IgE standpoint: a retrospective study.

SUMMARY: Background.Baseline total IgE levels have recently emerged as a prognostic factor for the clinical response to omalizumab in patients with severe chronic spontaneous urticaria (CSU). Objective. To investigate the main clinical features of patients with severe CSU from the standpoint of baseline total IgE. Methods. 153 patients (M/F 52/101; mean age 49,7 years) with severe CSU were studied. Based on IgE levels patients were divided into 5 subgroups and a ROC curve was built to define a threshold level for omalizumab response. Atopic status, thyroid autoimmunity, activation of the coagulation cascade, and response to omalizumab were studied as well. Results. The subgroups did not differ in terms of age and gender. Atopy prevailed in the subgroup showing elevated IgE. Thyroid autoimmunity and elevated D-dimer levels were similarly distributed in the five subgroups. 94 patients showed a prompt response to omalizumab. The likelihood of a prompt response was higher in males (p less than 0.01). In the subgroup showing the lowest IgE levels only 10% responded promptly to the drug; these proportions were 60%, 65%, 81% and 83% in the remaining groups. 66% of those in group A did not respond at all to omalizumab. A threshold IgE level of 18 IU/ml was detected for omalizumab response. Conclusions. Baseline total IgE show a high high prognostic value for omalizumab response with a threshold level of 18 IU/ml. Males seem more responsive to omalizumab. Most patients show a mixed clinical picture where signs of atopic status co-exist with signs of an autoimmune disease.

Nonsteroidal anti-inflammatory drugs hypersensitivity in chronic spontaneous urticaria in the light of its pathogenesis.

Summary: Up to 15% of patients with chronic spontaneous urticaria (CSU) experience severe exacerbations of their baseline cutaneous disease after taking nonsteroidal anti-inflammatory drugs that inhibit cycloxygenase-1 (COX-1) enzyme. These subjects are defined as having a NECD (NSAID-exacerbated cutaneous disease). The way NSAID hypersensitivity correlates with the different pathogenic mechanisms of CSU has not been investigated so far. 235 adults with severe CSU submitted to omalizumab treatment were studied. A rapid omalizumab response was considered as a marker of auto-allergic (Type I) CSU whereas patients showing a slow response or not responding at all were regarded as having a type IIb autoimmune disease. At the first visit medical history of tolerance to aspirin and/or other COX-1 inhibiting NSAID was ascertained. Duration of disease, atopic status, thyroid autoimmunity, CRP, D-dimer plasma levels, and total IgE were assessed appropriately. 23 (10%) were hypersensitive to NSAID. Patients with or without did not differ in any of the variable considered, and a similar proportion in the two groups showed type I or type IIb CSU. The study suggests that in CSU hypersensitivity to NSAID represents a phenomenon that is independent on the pathogenesis of the underlying skin disease.

D-dimer levels decline after immunosuppressive treatment rather than anticoagulant treatment in severe autoimmune chronic spontaneous urticaria.

Summary: Chronic spontaneous urticaria (CSU) is a common dermatological condition presenting with wheals and/or angioedema for more than 6 weeks. The role of autoimmunity and inflammation in the pathogenesis of CSU have been studied, but the precise mechanism remains unknown. Association with coagulation cascade has been suggested based on the observations of increased coagulation indicators such as serum D-dimer levels. We report an omalizumab refractory case of severe CSU with high D-Dimer levels that declined only after disease remission with cyclosporine treatment but not with anticoagulation. Activation of coagulation cascade occurs secondary to the pro-inflammatory state in CSU patients and the correlation between D-dimer levels and disease activity may indicate the need for more studies to better understand the relationship of D-dimer levels and Omalizumab resistance. Clinicians should consider this relationship in CSU patients with significant D-dimer levels before considering treatment with anticoagulants.

Evaluation and predictive value of IgE responses toward a comprehensive panel of house dust mite allergens using a new multiplex assay: a real-life experience on an Italian population.

Summary: Background. House dust mites (HDM) are among the most important allergen sources worldwide, representing a major cause of perennial allergic rhinitis and asthma. Aim. To evaluate the prevalence of IgE responses towards a comprehensive panel of HDM allergens and to evaluate the implications of molecular sensitization profiles on respiratory symptoms. Methods. 155 consecutive HDM-allergic patients (mean age: 27.5 years; range: 1-62; female: 63), 86 affected by rhinitis and 68 by asthma, were enrolled. Specific IgE reactivity to Der f 1, Der p 1, Der f 2, Der p 2, Der p 5, Der p 7, Der p 10, Der p 11, Der p 20, Der p 21 and Der p 23 was tested in patients' sera using the last version of the multiparametric assay Allergy Explorer (ALEX). Results. In all, major and minor allergens were positive, respectively, in 96.8% and 50.9% of the patients. Prevalence and IgE levels of Der f 1, Der f 2, Der p 1 and Der p 20 were significantly higher in asthmatic patients (p less than 0.05), whereas subjects negative for minor allergens resulted more frequently suffering from rhinitis (p = 0.0001). Asthmatic patients had IgE reactivity to a larger number of HDM allergens (mean 5.4; SD ± 2.3) than patients with only rhinitis (mean 4.2; SD ± 2.5) (p = 0.003), whereas no differences in the number of HDM positive molecules and in the specific IgE levels were found among different ages. Conclusions. This study confirms that the assessment of IgE to a comprehensive panel of HDM allergens defines different serological reactivity profiles that seem associated with different clinical presentations.

Why lipid transfer protein allergy is not a pollen-food syndrome: novel data and literature review.

Summary: Background.Based on the cross-reactivity between pollen lipid transfer proteins (LTPs) and the peach LTP, Pru p 3, it has been suggested that the pollen might initiate the LTP sensitization process. Objective. To establish whether LTP allergy can be considered as a pollen-food syndrome. Methods. The literature was reviewed and new data of component-resolved diagnosis from Italy obtained by both ISAC immunoassay and ImmunoCAP on large populations of LTP hypersensitive patients were provided and analyzed. Results. Among Pru p 3 reactors, patients positive for Art v 3 and Pla a 3 largely exceeded those sensitized to the respective major pollen allergens, Art v 1 and Pla a 1/Pla a 2. Pru p 3 reactivity remained stable around 80-90% at all ages, whereas Art v 3 and Ole e 7 recognition was missing in younger patients. Pru p 3 IgE exceeded IgE specific for pollen LTP at all ages. Inhibition studies carried out on LTP reactors showed that commercial extracts of mugwort and plane pollen were unable to inhibit significantly Pru p 3 IgE reactivity. In follow-up studies, baseline Pru p 3 IgE levels exceeded Art v 3 IgE levels in 84% of those sensitized to both allergens, and all patients positive to only one LTP allergen at baseline were sensitized to Pru p 3. Further, most of the patients who did not show any LTP reactivity at baseline became exclusive Pru p 3 reactors. On ImmunoCAP singleplex Pru p 3 IgE levels exceeded Art v 3 IgE levels in 89% of cases (p less than 0.0001). Most literature data were in keeping with these new observations. Conclusions. The evidence for LTP syndrome being a pollen-food syndrome is presently very thin. Our data do not rule out the possible sensitization to the protein, via the airways or the skin.

Sensitization to Gibberellin-Regulated Protein (Peamaclein) Among Italian Cypress Pollen-Sensitized Patients.

BACKGROUND AND OBJECTIVES: Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen-hypersensitive patients. Objective: We investigated monosensitization to peamaclein among Italian cypress pollen-allergic patients. MATERIAL AND METHODS: A total of 835 cypress pollen-hypersensitive patients from 28 Italian allergy centers underwent a thorough work-up to determine food-allergic reactions and performed skin prick testing with a commercial peach extract containing peamaclein. IgE to rPru p 3 was measured in peach reactors, and those with negative results were enrolled as potentially monosensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated using immunoblot and an experimental ImmunoCAP with rPru p 7. RESULTS: Skin prick tests were positive to peach in 163 patients (19.5%); however, 127 (77.9%) were excluded because they reacted to Pru p 3. Twenty-four patients (14.7%) corresponding to 2.8% of the entire study population) were considered potentially monosensitized to peamaclein. No geographic preference was observed. Seventeen of the 24 patients (70.8%) had a history of food allergy, mainly to peach (n=15). Additional offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3 of 18 putative peamaclein-allergic patients reacted to a band at about 7 kDa; an additional 4 patients reacted at about 50-60 kDa. Ten of 18 patients (56%) had a positive result for Pru p 7 on ImmunoCAP. CONCLUSION: Allergy and sensitization to peamaclein seem rare in Italy. Most patients react to peach, although other Rosaceae fruits and several citrus fruits may also be offending foods. Peach and cypress pollen probably also share cross-reacting allergens other than peamaclein.

The Chronic Urticaria Registry: rationale, methods and initial implementation.

BACKGROUND: Chronic urticaria (CU) is a common disease, characterized by the recurrent appearance of wheals, angioedema or both for more than 6 weeks. Its underlying biology is not well understood, and many patients do not obtain sufficient relief from recommended treatments. Patient registries are rapidly growing as a form of research, because they can provide powerful, data-driven insights about the epidemiology of diseases, real-world effectiveness of treatments, rare patient types, safety monitoring, healthcare costs and opportunities for quality improvement of healthcare delivery. OBJECTIVES: The Chronic Urticaria Registry (CURE) has been designed to improve the scientific understanding, clinical treatment and healthcare planning of CU patients. This report describes the rationale, methods and initial implementation of this registry. METHODS: Chronic Urticaria Registry is an ongoing, prospective, international, multicentre, observational, voluntary registry of patients with CU. Participation in CURE is open to any physician treating CU patients, regardless of location, medical specialty or type of practice setting. CURE aims to collect data on all CU patients, with no intentional selection or exclusion criteria. It collects baseline and follow-up data on the patient's demographics, history, symptoms, trigger and risk factors, therapies and healthcare utilization. RESULTS: Chronic Urticaria Registry is a landmark achievement of the global urticaria medical community. As of 26 February 2020, 39 centres around the world have joined the registry and 35 have entered baseline data on a total of 2946 patients. Publications of this data will be forthcoming soon. CONCLUSIONS: Chronic Urticaria Registry is eagerly seeking the participation of more physicians and the support of more governmental, charitable and commercial sponsors from around the world. Here, in this paper, we invite other physicians to join this unique project to improve the lives of patients with CU.

Omalizumab in severe chronic urticaria: are slow and non-responders different?

SUMMARY: Background. The response to Omalizumab by patients with severe Chronic Spontaneous Urticaria (CSU), may be rapid, slow, or absent. An early response has been associated with an IgE-mediated auto-allergic pathogenic mechanism, whereas little is known about slow and non-responders. Objective. To compare CSU patients responding slowly or non-responding to Omalizumab. Methods. Forty-six patients showing a slow (n= 23) or absent (n= 23) response to Omalizumab out of a cohort of 170 patients with severe CSU (UAS-7 major 30) were studied. Several baseline clinical and serological parameters were compared in the two groups. Results. Apart from a lower prevalence of atopic diseases (p minor 0.05) and a slightly higher prevalence of thyroid autoimmunity in non-responders, the two groups were similar in terms of clinical and serological features. The majority of patients in both groups showed low baseline total IgE levels. Conclusions. Patients with severe CSU showing a slow response or not responding at all to omalizumab show impressive similarities. It is currently not possible to predict whether patients with severe CSU and low IgE levels will show a slow response or will not respond to anti-IgE treatment.

Cypress pollen allergy in Milan: the story of an ongoing growth.

SUMMARY: Cypress pollen allergy was virtually absent in Lombardy about 30 years ago. A 15-year clinical survey on cypress pollen sensitization and allergy in the area north of Milan reveals that both cypress pollen sensitization and allergy increased steadily from 2003 to 2017 along with the prevalence of clinical allergy over sensitization. The pollen concentration data, recorded up from 1995 showed a dramatic increase in cypress Annual Pollen Index up from the beginning of the new millennium. Cypress pollen represents now a relevant allergen source in this area.

Urticaria and coronavirus infection: a lesson from SARS-CoV-2 pandemic.

Summary: Urticaria is a condition involving both skin and mucosal tissues characterized by the presence of wheals and/or angioedema. The acute form has been related to allergic reactions to drugs or foods, interaction with chemicals, or infections. We reviewed the association of urticaria with coronavirus infections. This review was carried out by the use of two search engines for published original articles, employing two key terms correlated to urticaria and viruses: "urticaria" and one term linked to each virus. The research of the relationships between SARS-CoV-2 and urticaria produced 18 papers (including a total of 114 cases). Surprisingly, the search for cases of urticaria in patients with SARS-CoV or MERS produced no results. We tried to interpret this discrepancy and attempted to analyze the possible pathogenesis of urticaria lesions in SARS-CoV-2.

Evaluation of two commercial peach extracts for skin prick testing in the diagnosis of hypersensitivity to lipid transfer protein. A multicenter study.

Summary: The clinical usefulness of two commercial peach extracts for SPT (by Lofarma SpA and ALK-Abellò, respectively) was compared in a multicenter study carried out in Italy. Peach allergic patients were tested with the two extracts in parallel and underwent the detection of IgE specific for all three peach allergens currently available (Pru p1, Pru p3, and Pru p4, respectively). The two extracts were almost identical in terms of sensitivity and specificity, being able to detect virtually all patients sensitized to stable peach allergens (lipid transfer protein (LTP) and, presumably, peamaclein) but scoring negative in patients exclusively sensitive to labile allergens (either PR-10 and/or profilin). Thus, the two extracts represent an excellent tool to carry out a preliminary component-resolved diagnosis of peach allergy at the first patient visit.

Co-occurrence of IgE and IgG autoantibodies in patients with chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) pathogenesis shows a complex and still unclear interplay between immunoglobulin (Ig)G- and IgE-mediated autoimmunity, leading to mast cell and basophil degranulation and wheal formation. The objective of this study was to evaluate at the same time IgE- and IgG-reactivity to well recognized and recently reported autoantigens in CSU patients, and to assess the effects of such reactivity on response to the anti-IgE monoclonal antibody omalizumab. Twenty CSU patients underwent omalizumab treatment. Urticaria activity score 7 (UAS7) was recorded at baseline and at different drug administration time-points for categorizing early-, late- or non-responders. At baseline, sera from the 20 patients and from 20 controls were tested for IgE and IgG autoantibodies to high- and low-affinity IgE receptors (FcεRI and FcεRII), tissue factor (TF) and thyroglobulin (TG) by immunoenzymatic methods. Antibody levels were compared with those of controls and analysed according to response. Eighteen patients were omalizumab responders (11 early and seven late), while two were non-responders. More than 50% of patients had contemporary IgE and IgG to at least to one of the four different autoantigens. Late responders showed higher levels of both anti-TF IgE and IgG than early responders (P = 0·011 and P = 0·035, respectively). Twenty-five per cent of patients had levels of anti-FcεRI IgE, exceeding the upper normal limit, suggesting that it could be a novel auto-allergen in CSU. In CSU, there is an autoimmune milieu characterized by the co-existence of IgE and IgG autoantibodies to the same antigen/allergen, particularly in late responders to omalizumab, possibly explaining the slower response.