Atopy and Response to Omalizumab Treatment in Chronic Spontaneous Urticaria.

INTRODUCTION: The possible influence of sensitization to aeroallergens on omalizumab response in chronic spontaneous urticaria (CSU) has been insufficiently investigated. This study's aim was to investigate atopy's influence on omalizumab response in CSU patients. METHOD: Retrospective study of CSU patients followed at a Portuguese Urticaria Center of Reference and Excellence (UCARE), treated with omalizumab for at least 6 months, between 2015 and 2022. At T0, all patients underwent quantification of specific immunoglobulin E (IgE) for total extract of most prevalent aeroallergens (ImmunoCAP Thermo Fisher Scientific®) and were divided in 2 groups, according to their response to omalizumab during the first 16 weeks of treatment: responders (R) (UAS7 <7) versus partial (PR) (UAS7 = 7-15) and nonresponders (UAS7 >15). R were further classified as fast (FR) (4-6 weeks) and slow responders (SR) (12-16 weeks). Total serum IgE, circulating eosinophil, and basophil counts were compared between groups at T0. p < 0.05 was considered statistically significant (SPSS® v25.0). RESULTS: Ninety-six patients (80% female) were studied, mean age 49 ± 14 years. Median CSU duration pre-omalizumab was 3 (0.6-20) years and mean omalizumab treatment duration was 3.7 ± 2.3 years. 38 (40%) had concomitant chronic inducible urticaria and 72 (75%) angioedema. Based on positive results of the specific IgE assay, 35 patients (36%) were considered atopic. Most patients (n = 30; 86%) were sensitized to house dust mites (HDM) (Dermatophagoides farinae = 28, Dermatophagoides pteronyssinus = 27, Blomia tropicalis = 19, Lepidoglyphus destructor = 17), followed by pollens (n = 12; 34%) (mixture of grasses = 10, Olea europaea = 7, Parietaria officinalis = 6), epithelia (n = 9; 26%) (dog = 8, cat = 7), and fungi (Alternaria alternata = 4; 11%). Eight patients (23%) were monosensitized to HDM and 4 (11%) to pollens. No significant association was found between aeroallergen sensitization and CSU duration, concomitant chronic inducible urticaria, or angioedema. Atopic patients featured significantly higher levels of baseline total serum IgE than nonatopic (469 vs. 94 U/mL, respectively; p = 0.0009). Mean baseline counts of eosinophils and basophils were not significantly different between atopic and non-atopic, respectively: eosinophils (128 vs. 121/mm3) and basophils (26 vs. 28/mm3). Regarding response to omalizumab, most patients (58; 60%) were responders: FR - 46 (79%); SR - 12 (21%). There was no significant association between aeroallergen sensitization and omalizumab response or speed of response. CONCLUSIONS: As far as we know, this is the first study exploring the influence of atopy sensitization pattern on omalizumab response in CSU. According to our results, presence of atopy/sensitization pattern does not influence omalizumab response in CSU patients.

Anti-TPO IgG/Total IgE Ratio: Biomarker for Omalizumab Response Prediction in Chronic Spontaneous Urticaria.

BACKGROUND: According to recently published data, low total IgE, elevated IgG-anti-TPO, and a high IgG-anti-TPO/total IgE ratio are good biomarkers for subtype IIb autoimmune chronic spontaneous urticaria (CSU), which is frequently refractory to antihistamines and omalizumab. OBJECTIVES: The aim of the study was to evaluate IgG-anti-TPO/total IgE ratio's utility in omalizumab response prediction. METHODS: Retrospective study of CSU patients treated with omalizumab at a UCARE between January 2009 and February 2022. Patients were grouped according to response in the first 16 weeks of treatment: responders UAS7 < 7 versus partial/non-responders UAS7≥7. Total IgE, IgG-anti-TPO, and IgG-anti-TPO/total IgE ratio were compared. Other inflammatory biomarkers - eosinophils, basophils, C-reactive protein, erythrocyte sedimentation rate, and d-dimer - were analyzed. STATISTICAL ANALYSIS: SPSS® (v25.0), p < 0.05 statistically significant. RESULTS: Total of 175 patients, 140 (80%) women, median age 49 [9-88] years, mean CSU duration pre-omalizumab 5.6 ± 8.2 [0-54] years, omalizumab duration 3.2 ± 2.5 [0-12] years. 116 (66%) had angioedema, 77 (44%) inducible chronic urticaria, 60 (34%) atopy, 24 (14%) autoimmune disease. With omalizumab 300 mg q4 weeks, 69% were responders and 31% partial/non-responders. Although not reaching significant differences, mean total IgE values were lower and mean IgG-anti-TPO values were higher in partial/non-responders versus responders (152 vs. 242 kU/L, p = 0.207, and 38.3 vs. 25.7 U/mL, p = 0.408, respectively). A higher IgG-anti-TPO/total IgE ratio was significantly associated with poorer response to omalizumab (p = 0.040). A cut-off >0.154 increased 10 times the odd of poorer response [95% CI 4.62-22], AUC 0.872, p < 0.001, with 87.7% sensitivity, although the low specificity (22.4%) does not allow the assumption of response with values <0.154. Other laboratory biomarkers did not show significant differences between partial/non-responders versus responders. CONCLUSIONS: A high IgG-anti-TPO/total IgE ratio was a good biomarker of poor response to omalizumab in our CSU cohort, with a cut-off >0.154 increasing 10 times the odd of poorer response.

Identification of a thaumatin-like protein as a new allergen in persimmon (Diospyros kaki) with cross-reactivity with banana (Musa acuminata) / Identificação de uma proteína semelhante à taumatina como um novo alérgeno no caqui (Diospyros kaki) com reatividade cruzada com a banana (Musa acuminata)

Allergy to persimmon (Diospyros kaki ) has been only rarely reported. The antigenic composition of the fruit is not entirely known. Thaumatin-like proteins (TLPs) have been described as allergens in pollens and various fruits, such as kiwi and banana, but not in persimmon. We report the case of a 22-year-old man, with persistent moderate-to-severe allergic rhinitis, sensitized to house dust mites. The patient describes an episode of oral mucosa and ear canal pruritus, followed by diffuse urticaria, which rapidly evolved to dysphonia, dyspnea, and dizziness, after eating raw persimmon. A few months later he developed similar cutaneous symptoms accompanied by nausea, vomiting, abdominal colic, and hypotension immediately after the intake of banana. The prick-prick test with raw persimmon and banana were positive, as well as the serum specific IgE to the extract of these fruits. The ImmunoCAP ISAC_112i test demonstrated a positive specific IgE against Act d 2 (kiwi thaumatin), which is homologous to banana TLP (Mus a 4). Serum IgE inhibition test with "sponge" of Diospyros kaki ImmunoCAP (f301) showed partial inhibition (40%) of IgE to Act d 2. This raises the suspicion that a TLP is at least partially responsible for the referred sensitization. This patient is sensitized to Diospyros kaki and Musa acuminata. An anaphylactic reaction to consumed persimmon, presumably as a result from cross-allergy with banana thaumatin was diagnosed in our patient. Thaumatin has not been previously described as an allergen of persimmon with cross-reactivity with banana, and in vitro with Act d 2 (kiwi TLP).

A alergia ao caqui (Diospyros kaki ) tem sido raramente documentada, não sendo a composição antigênica da fruta totalmente conhecida. Proteínas semelhantes à taumatina (TLPs) foram descritas como alergênicos em pólens e várias frutas, como no kiwi e banana, mas não no caqui. Apresenta-se o caso de um doente de 22 anos, com rinite alérgica persistente moderadagrave, sensibilizado a ácaros do pó doméstico. O doente refere episódio de prurido na mucosa oral e canal auditivo, seguido de urticária generalizada, que rapidamente evoluiu para disfonia, dispneia e tontura, após ingestão de caqui. Poucos meses depois, desenvolveu sintomas cutâneos semelhantes, acompanhados de náuseas, vómitos, cólica abdominal e hipotensão imediatamente após ingestão de uma banana. O teste cutâneo por picada com caqui e banana em natureza foram positivos, bem como o doseamento de IgE específica. O teste ImmunoCAP ISAC_112i identificou a presença de IgE específica para Act d 2 (taumatina do kiwi), homóloga da TLP da banana (Mus a 4). O estudo de inibição ImmunoCAP ISAC com "esponja" de Diospyros kaki (f301) produziu uma inibição parcial (40%) da ligação de IgE a Act d 2, permitindo presumir que uma proteína semelhante à taumatina é, pelo menos, parcialmente responsável pela referida sensibilização. Este doente encontra-se sensibilizado a Diospyros kaki e Musa acuminata. Uma anafilaxia ao caqui ingerido, presumivelmente resultante de reatividade cruzada com a taumatina da banana foi diagnosticada. Não estão descritas na literatura TLPs como alergênicos do caqui com reatividade cruzada com a banana e com Act d 2 in vitro (TLP do kiwi).