| 1. |
- Albinsson, Sofie, 1992
(författare)
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A Study of Eosinophils – From the Human Thymus to Eosinophilic Esophagitis
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Eosinophils are cells of the innate immune system. They primarily reside within tissues and are most numerous in the gastrointestinal tract but are absent from the healthy esophagus. During the inflammatory disease eosinophilic esophagitis, eosinophils infiltrate the esophagus but their function is unknown. Eosinophils also reside within the human thymus, although their function within this organ dedicated to T cell development is unclear. This thesis is a study of eosinophils resident within the human thymus and of the disease eosinophilic esophagitis. The aim was to increase knowledge on the eosinophil granulocyte and to improve healthcare of patients afflicted with eosinophilic esophagitis. In paper I, molecular patterns of eosinophils in the blood of patients with eosinophilic esophagitis were combined with patient-reported outcomes to yield a multivariate model capable of separating patients who had responded to topical corticosteroid treatment from patients who did not respond to treatment. The use of such multivariate models based on less invasive methods than endoscopic procedures to evaluate success of therapy could improve patient care and patients’ quality of life. Paper II was also focused on the advancement of patient care. The first Swedish instrument specifically developed for assessment of symptom severity of eosinophilic esophagitis was translated and validated in order to improve clinical assessment of the disease among Swedish adults. In paper III, esophageal eosinophils found in biopsies from patients with eosinophilic esophagitis were studied using fluorescent immunohistochemistry. These analyses revealed associations between eosinophils and CD4+ T cells, the presence of CD16+ “suppressive” eosinophils, and massive release of extracellular galectin-10 within the esophageal mucosa. Tissue resident eosinophils were further studied in human thymus of thymectomized children in papers IV and V. In paper IV, eosinophils were studied using fluorescent immunohistochemistry to investigate their maturity, distribution, and cellular interactions within the thymus. Immature and proliferating eosinophils were found, as well as mature cells, and the primary location of thymic eosinophils was in the corticomedullary junction. In paper V, thymic eosinophils were phenotypically characterized using cytometry by time-of-flight and their interactions with thymocytes were studied by co-culture experiments of fluorescence-activated cell sorted thymic eosinophils and thymocytes of the double-positive (CD4+CD8+), CD4 single-positive, and CD8 single-positive stages. The thymic eosinophils displayed a distinct phenotype compared to blood eosinophils and the thymic eosinophils were capable of directing thymocytes toward the CD4 single-positive phenotype. In this thesis, T cell suppression is presented as a possible function of eosinophils in eosinophilic esophagitis and thymic eosinophils are shown to be specialized cells that can affect the thymocyte development process.
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| 2. |
- Albinsson, Sofie, 1992, et al.
(författare)
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Eosinophils interact with thymocytes and proliferate in the human thymus
- 2021
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Ingår i: European journal of immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 51:6, s. 1539-1541
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Albinsson, Sofie, 1992, et al.
(författare)
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Extracellular distribution of galectin-10 in the esophageal mucosa of patients with eosinophilic esophagitis
- 2023
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Ingår i: CLINICAL AND EXPERIMENTAL IMMUNOLOGY. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 212:2, s. 147-155
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Tidskriftsartikel (refereegranskat)abstract
- CD16+ eosinophils and large amounts of extracellular vesicles containing galectin-10, a T-cell suppressive eosinophil protein, were found in the esophageal mucosa of patients with active eosinophilic esophagitis. Both the CD16+ eosinophils and the released galectin-10-containing extracellular vesicles disappeared in successfully treated patients but remained in the mucosa of the non-responders to treatment. 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.
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| 4. |
- Albinsson, Sofie, 1992, et al.
(författare)
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Patient-Reported Dysphagia in Adults with Eosinophilic Esophagitis: Translation and Validation of the Swedish Eosinophilic Esophagitis Activity Index
- 2022
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Ingår i: Dysphagia. - : Springer Science and Business Media LLC. - 0179-051X .- 1432-0460. ; 37, s. 286-296
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Albinsson, Sofie, 1992, et al.
(författare)
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Validation of the Swedish Watson Dysphagia Scale for adult patients with eosinophilic esophagitis
- 2022
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Ingår i: Diseases of the Esophagus. - : Oxford University Press (OUP). - 1120-8694 .- 1442-2050. ; 35:7
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Larsson, Helene, et al.
(författare)
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Investigating immune profile by CyTOF in individuals with long-standing type 1 diabetes
- 2023
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Ingår i: Scientific Reports. - : Nature Research. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes (T1D) is an autoimmune disease caused by T-cell mediated destruction of pancreatic beta cells. Eosinophils are found in pancreatic tissue from individuals with T1D. Eosinophilic suppression of T cells is dependent of the protein galectin-10. Little is known when it comes to the role of eosinophil granulocytes in type 1 diabetes. Here we show that individuals with long-standing T1D had lower levels of galectin-10hi eosinophils and a subgroup of galectin-10hi eosinophils were entirely absent in all T1D patients. In addition, 7% immature eosinophils were present in the circulation of T1D patients whereas 0.8% in healthy individuals. Furthermore, higher levels of CD4+CD8+ T cells and Th17 cells were observed in patients with T1D. Blood samples from 12 adult individuals with long-standing T1D and 12 healthy individuals were compared using cytometry by time-of-flight. Lower levels of galectin-10hi eosinophils, which are potent T cell suppressors, in individuals with T1D could indicate that activated T cells are enabled to unrestrictedly kill the insulin producing beta cells. This is the first study showing absence of galectin-10hi eosinophilic subgroup in individuals with T1D compared with healthy controls. This study is a first important step toward unraveling the role of the eosinophils in patients with T1D.
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| 7. |
- Lingblom, Christine, 1984, et al.
(författare)
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Patient-Reported Outcomes and Blood-Based Parameters Identify Response to Treatment in Eosinophilic Esophagitis
- 2021
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Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 0163-2116 .- 1573-2568. ; 66, s. 1556-1564
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Mohammad, Ghayeb, et al.
(författare)
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Isolated eosinophilic myometritis: A case report of an extremely rare phenomenon
- 2021
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Ingår i: International Journal of Gynecological Pathology. - 0277-1691 .- 1538-7151. ; 41:3
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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