Distinct populations of eosinophils in the human thymus with capacity to modulate thymocyte maturation.

Local differentiation of eosinophil precursors occurs in the human thymus. Thymic eosinophils are often positioned in the corticomedullary junction between the CD4+ CD8+ double-positive (DP) thymocytes and the CD4+ or CD8+ single-positive (SP) thymocytes. The aims of this study were to (1) determine if there are distinct thymic eosinophil populations that differ from the blood eosinophil populations and (2) evaluate the capacity of thymic eosinophils to promote the development of SP thymocytes from DP thymocytes. Thymic and blood eosinophils from thymectomized infants (n = 7) were compared regarding the expression of 34 molecules using cytometry by time-of-flight (CyTOF). In addition, FACS-sorted thymic eosinophils were co-cultured with autologous CD3/CD28-stimulated DP, CD4 SP, and CD8 SP thymocytes and analysed by flow cytometry and CyTOF. X-shift clustering analysis and viSNE dimensionality reduction were performed. Seven eosinophil populations were identified within the blood and thymus, respectively, five of which were specific for either tissue. Whereas the blood eosinophil populations varied between individuals, the thymic eosinophil populations were more uniform. The eosinophil-thymocyte co-cultures resulted in (1) an increase in CD4 SP thymocytes when eosinophils were cultured with DP thymocytes, (2) decreased frequency of CD8 SP thymocytes when these were cultured with eosinophils, and (3) a more mature thymic phenotype when eosinophils were cultured with CD4 SP thymocytes. Thymic eosinophils are a specialized population of eosinophils with a distinct phenotype that separates them from their blood counterparts, and in vitro they appear to favour CD4 SP thymocyte development to the detriment of CD8 SP thymocytes.

The presence of serum anti-SARS-CoV-2 IgA appears to protect primary health care workers from COVID-19.

The patterns of humoral and cellular responses to SARS-CoV-2 were studied in Swedish primary health care workers (n = 156) for 6 months during the Covid-19 pandemic. Serum IgA and IgG to SARS-CoV-2, T-cell proliferation and cytokine secretion, demographic and clinical data, PCR-verified infection, and self-reported symptoms were monitored. The multivariate method OPLS-DA was used to identify immune response patterns coupled to protection from Covid-19. Contracting Covid-19 was associated with SARS-CoV-2-specific neutralizing serum IgG, T cell, IFN-γ, and granzyme B responses to SARS-CoV-2, self-reported typical Covid-19 symptoms, male sex, higher BMI, and hypertension. Not contracting Covid-19 was associated with female sex, IgA-dominated, or no antibody responses to SARS-CoV-2, airborne allergy, and smoking. The IgG-responders had SARS-CoV-2-specific T-cell responses including a cytotoxic CD4+ T-cell population expressing CD25, CD38, CD69, CD194, CD279, CTLA-4, and granzyme B. IgA-responders with no IgG response to SARS-CoV-2 constituted 10% of the study population. The IgA responses were partially neutralizing and only seen in individuals who did not succumb to Covid-19. To conclude, serum IgG-dominated responses correlated with T-cell responses to SARS-CoV-2 and PCR-confirmed Covid-19, whereas IgA-dominated responses correlated with not contracting the infection.

Extracellular distribution of galectin-10 in the esophageal mucosa of patients with eosinophilic esophagitis.

Eosinophilic esophagitis is a T-cell-driven allergic condition hallmarked by eosinophil infiltration of the esophagus. Eosinophils exposed to proliferating T cells release galectin-10 and have T-cell suppressive function in vitro. The aims of this study were to evaluate if eosinophils co-localize with T cells and release galectin-10 in the esophagus of patients with eosinophilic esophagitis. Esophageal biopsies from 20 patients with eosinophilic esophagitis were stained for major basic protein, galectin-10, CD4, CD8, CD16, and CD81 and analyzed by immunofluorescence confocal microscopy before and after topical corticosteroid treatment. CD4+ T-cell numbers decreased in the esophageal mucosa of responders to treatment but not in the non-responders. Suppressive (CD16+) eosinophils were present in the esophageal mucosa of patients with active disease and decreased after successful treatment. Unexpectedly, eosinophils and T cells were not in direct contact with each other. Instead, the esophageal eosinophils released large amounts of galectin-10-containing extracellular vesicles and featured cytoplasmic projections that contained galectin-10, both of which disappeared from the esophagus of the responders but remained in the non-responders. To conclude, the presence of CD16+ eosinophils together with the massive release of galectin-10-containing extracellular vesicles in the esophageal mucosa might indicate that eosinophils exert T-cell suppression in eosinophilic esophagitis.

Eosinophils interact with thymocytes and proliferate in the human thymus.

Eosinophils differentiate and mature in the thymus, outside of the bone marrow, in healthy individuals. Locally developed thymic eosinophils may contribute to the maturation and selection of human thymocytes.

Isolated Eosinophilic Myometritis: A Case Report of an Extremely Rare Phenomenon.

Increased number of eosinophils in the uterus has been reported under physiological and pathologic conditions. However, eosinophilic infiltration limited to the myometrium is very unusual. A rare finding of isolated eosinophilic infiltration in the myometrium without involvement of endometrium or pathologies in the cervix or ovaries was observed in a 31-yr-old woman seeking medical attention for unexplained infertility, abnormal uterine bleeding, and dysmenorrhea. The patient had no allergies, parasitic disease, or other systemic disorders. This rare manifestation of eosinophilic infiltration expands the differential diagnosis of inflammatory conditions of the myometrium in patients with gynecological issues.

Validation of the Swedish Watson Dysphagia Scale for adult patients with eosinophilic esophagitis.

BACKGROUND: The Swedish Watson Dysphagia Scale (S-WDS) has been used to assess dysphagia in patients with eosinophilic esophagitis (EoE) but has not been validated for this patient group. The aim of this study was to validate the S-WDS for adult patients with EoE. METHODS: Ninety-seven Swedish adult patients with EoE and 97 controls without dysphagia filled out the S-WDS, the Swedish Eosinophilic Esophagitis Activity Index (S-EEsAI) and a set of supplementary questions. The reliability of the S-WDS was evaluated using Cronbach's alpha, Pearson correlation of items and total score, and test-retest analysis (n = 29). Validity was investigated using Spearman correlations of the S-WDS items, S-EEsAI domains and a self-assessment score, and by investigating floor and ceiling effects. RESULTS: The Cronbach's alpha of the S-WDS was 0.77 and all items demonstrated moderate to strong correlation to the S-WDS score (r = 0.40-0.81) indicative of sufficient reliability of the instrument. In addition, the test-retest results reflected excellent reliability with an intraclass correlation coefficient of 0.85 for the S-WDS score. Adequate validity of the instrument was demonstrated, the S-WDS score correlated moderately with the self-assessment score and with 4/6 S-EEsAI domains, and strongly with the remaining two domains. Floor effects were more common for liquids and soft-textured foods and ceiling effects increased with increasing food consistency. The S-WDS scores of the patient group were significantly different from those of the nondysphagia control group (P < 0.001). CONCLUSION: The S-WDS instrument is an appropriate and valid instrument for assessment of dysphagia in patients with EoE.

Patient-Reported Dysphagia in Adults with Eosinophilic Esophagitis: Translation and Validation of the Swedish Eosinophilic Esophagitis Activity Index.

The lack of a Swedish patient-reported outcome instrument for eosinophilic esophagitis (EoE) has limited the assessment of the disease. The aims of the study were to translate and validate the Eosinophilic Esophagitis Activity Index (EEsAI) to Swedish and to assess the symptom severity of patients with EoE compared to a nondysphagia control group. The EEsAI was translated and adapted to a Swedish cultural context (S-EEsAI) based on international guidelines. The S-EEsAI was validated using adult Swedish patients with EoE (n = 97) and an age- and sex-matched nondysphagia control group (n = 97). All participants completed the S-EEsAI, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Oesophageal Module 18 (EORTC QLQ-OES18), and supplementary questions regarding feasibility and demographics. Reliability and validity of the S-EEsAI were evaluated by Cronbach's alpha and Spearman correlation coefficients between the domains of the S-EEsAI and the EORTC QLQ-OES18. A test-retest analysis of 29 patients was evaluated through intraclass correlation coefficients. The S-EEsAI had sufficient reliability with Cronbach's alpha values of 0.83 and 0.85 for the "visual dysphagia question" and the "avoidance, modification and slow eating score" domains, respectively. The test-retest reliability was sufficient, with good to excellent intraclass correlation coefficients (0.60-0.89). The S-EEsAI domains showed moderate correlation to 6/10 EORTC QLQ-OES18 domains, indicating adequate validity. The patient S-EEsAI results differed significantly from those of the nondysphagia controls (p < 0.001). The S-EEsAI appears to be a valid and reliable instrument for monitoring adult patients with EoE in Sweden.

Patient-Reported Outcomes and Blood-Based Parameters Identify Response to Treatment in Eosinophilic Esophagitis.

BACKGROUND: Noninvasive methods to assess treatment response in eosinophilic esophagitis are needed. AIMS: Our aim was to determine whether a blood-based biomarker panel centered on immune parameters could identify histologic response to treatment in eosinophilic esophagitis patients. METHODS: A pilot study involving adult patients with active eosinophilic esophagitis recruited at two Ear, Nose, Throat clinics in Sweden was designed. The patients (n = 20) donated blood and esophageal biopsies and filled in three questionnaires before and after a 2-month course of topical corticosteroids. Blood samples were analyzed for absolute levels of granulocytes and T cells and the fractions of eosinophils expressing 10 different surface markers by flow cytometry. All data were analyzed by multivariate methods of pattern recognition. RESULTS: Multivariate modeling revealed that a combination of 13 immune parameters and 10 patient-reported outcome scores were required to create a model capable of separating responders (n = 15) from non-responders (n = 5). Questions regarding symptoms of esophageal dysfunction and capacity to eat certain foods from two of the questionnaires were discriminatory in the multivariate model, as were absolute counts of T cells, eosinophils, and eosinophil expression of activation markers and cell adhesion molecules. CONCLUSIONS: A combination of blood-based immune parameters and directed questions may prove helpful to monitor response to treatment, perhaps reducing the need for repeat endoscopies in eosinophilic esophagitis patients in the future.