| 1. |
- Borgström, Emilie W., et al.
(författare)
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Three Adult Cases of STAT1 Gain-of-Function with Chronic Mucocutaneous Candidiasis Treated with JAK Inhibitors
- 2023
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Ingår i: Journal of Clinical Immunology. - : Springer. - 0271-9142 .- 1573-2592. ; 43, s. 136-150
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Tidskriftsartikel (refereegranskat)abstract
- Purpose; The aim of this study was to characterize clinical effects and biomarkers in three patients with chronic mucocutaneous candidiasis (CMC) caused by gain-of-function (GOF) mutations in the STAT1 gene during treatment with Janus kinase (JAK) inhibitors.Methods: Mass cytometry (CyTOF) was used to characterize mononuclear leukocyte populations and Olink assay to quantify 265 plasma proteins. Flow-cytometric Assay for Specific Cell-mediated Immune-response in Activated whole blood (FASCIA) was used to quantify the reactivity against Candida albicans.Results: Overall, JAK inhibitors improved clinical symptoms of CMC, but caused side effects in two patients. Absolute numbers of neutrophils, T cells, B cells, and NK cells were sustained during baricitinib treatment. Detailed analysis of cellular subsets, using CyTOF, revealed increased expression of CD45, CD52, and CD99 in NK cells, reflecting a more functional phenotype. Conversely, monocytes and eosinophils downregulated CD16, consistent with reduced inflammation. Moreover, T and B cells showed increased expression of activation markers during treatment. In one patient with a remarkable clinical effect of baricitinib treatment, the immune response to C. albicans increased after 7 weeks of treatment. Alterations in plasma biomarkers involved downregulation of cellular markers CXCL10, annexin A1, granzyme B, granzyme H, and oncostatin M, whereas FGF21 was the only upregulated marker after 7 weeks. After 3 months, IFN-gamma and CXCL10 were downregulated.Conclusions: The clinical effect of JAK inhibitor treatment of CMC is promising. Several biological variables were altered during baricitinib treatment demonstrating that lymphocytes, NK cells, monocytes, and eosinophils were affected. In parallel, cellular reactivity against C. albicans was enhanced.
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| 2. |
- Fasth, Anders, 1945, et al.
(författare)
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Quality of life and health-care resource utilization among children with primary immunodeficiency receiving home treatment with subcutaneous human immunoglobulin.
- 2008
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Ingår i: Journal of clinical immunology. - : Springer Science and Business Media LLC. - 0271-9142 .- 1573-2592. ; 28:4, s. 370-8
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Among patients with antibody deficiency, patient-reported outcomes are important for choosing between equally effective treatment regimens. PATIENTS AND METHODS: Twelve children (1.7-17.1 years) with primary immunodeficiency were switched from hospital-based intravenous IgG treatment to home treatment with subcutaneous IgG. Quality of life (Child Health Questionnaire) and health-care resource utilization were assessed at baseline and after 3 and 6 months. RESULTS: From the parents' perspective, significant improvements were seen after 6 months for mental health (median difference; 95% confidence interval, 15.0; 0.0, 22.5); change in health (1.0; 0.0, 2.0); and family activities (12.5; 2.1, 25.0). From the children's' perspective, significant improvements were seen for role/social limitations-emotional at 3 (22.2; 11.1, 33.3) and 6 months (22.2; 11.1, 66.7) and global health at 6 months (35.0; 15.0, 55.0). There were no significant improvements in other concepts. Subcutaneous IgG treatment significantly reduced absence days, days spent on hospital/physician visits, and health-care-related expenses. CONCLUSION: Switching to home-based subcutaneous IgG treatment led to significant improvements in quality of life and substantial cost savings.
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| 3. |
- Fernandes, Juliana Folloni, et al.
(författare)
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Transplantation of Hematopoietic Stem Cells for Primary Immunodeficiencies in Brazil: Challenges in Treating Rare Diseases in Developing Countries.
- 2018
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Ingår i: Journal of clinical immunology. - : Springer Science and Business Media LLC. - 1573-2592 .- 0271-9142. ; 38:8, s. 917-926
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Tidskriftsartikel (refereegranskat)abstract
- The results of hematopoietic stem cell transplant (HSCT) for primary immunodeficiency diseases (PID) have been improving over time. Unfortunately, developing countries do not experience the same results. This first report of Brazilian experience of HSCT for PID describes the development and results in the field. We included data from transplants in 221 patients, performed at 11 centers which participated in the Brazilian collaborative group, from July 1990 to December 2015. The majority of transplants were concentrated in one center (n = 123). The median age at HSCT was 22 months, and the most common diseases were severe combined immunodeficiency (SCID) (n = 67) and Wiskott-Aldrich syndrome (WAS) (n = 67). Only 15 patients received unconditioned transplants. Cumulative incidence of GVHD grades II to IV was 23%, and GVHD grades III to IV was 10%. The 5-year overall survival was 71.6%. WAS patients had better survival compared to other diseases. Most deaths (n = 53) occurred in the first year after transplantation mainly due to infection (55%) and GVHD (13%). Although transplant for PID patients in Brazil has evolved since its beginning, we still face some challenges like delayed diagnosis and referral, severe infections before transplant, a limited number of transplant centers with expertise, and resources for more advanced techniques. Measures like newborn screening for SCID may hasten the diagnosis and ameliorate patients' conditions at the moment of transplant.
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| 4. |
- Grindebacke, Hanna, 1977, et al.
(författare)
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Specific Immunotherapy to Birch Allergen Does not Enhance Suppression of Th2 Cells by CD4(+)CD25 (+) Regulatory T Cells During Pollen Season.
- 2009
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Ingår i: Journal of clinical immunology. - : Springer Science and Business Media LLC. - 1573-2592 .- 0271-9142. ; 29:6, s. 752-60
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The aim of this study was to investigate the suppressive capacity of CD25(+) regulatory T cells on birch allergen-induced T-cell responses during the first birch pollen season after initiation of specific immunotherapy (SIT). METHODS: CD25(pos) and CD25(neg) T cells were purified from blood of birch-allergic SIT patients and birch-allergic controls, stimulated with birch pollen extract, and analyzed for T-cell proliferation and production of interferon gamma (IFN-gamma), interleukin (IL)-5 and IL-10. RESULTS: We show that allergen-induced proliferation and IFN-gamma production were suppressed equally well by CD25(pos) T cells from SIT patients and controls, while the IL-5 production was not suppressed by either of the groups. IL-10 levels were higher in SIT patients relative to controls only when CD25(neg) and CD25(pos) were cultured together. Furthermore, neither FOXP3 levels nor proportions of CD25(high) T cells were enhanced in SIT patients compared to allergic controls. DISCUSSION: These results suggest that the Th2-suppressive capacity of allergen-stimulated CD25(pos) Treg in vitro is not improved by SIT in spite of increased IL-10 production from T cells.
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| 5. |
- Israni, Muskan, et al.
(författare)
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Current Transition Practice for Primary Immunodeficiencies and Autoinflammatory Diseases in Europe: a RITA-ERN Survey.
- 2023
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Ingår i: Journal of clinical immunology. - : Springer Science and Business Media LLC. - 0271-9142 .- 1573-2592. ; 43:1, s. 206-216
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Tidskriftsartikel (refereegranskat)abstract
- Due to the absence of curative treatments for inborn errors of immunity (IEI), children born with IEI require long-term follow-up for disease manifestations and related complications that occur over the lifespan. Effective transition from pediatric to adult services is known to significantly improve adherence to treatment and long-term outcomes. It is currently not known what transition services are available for young people with IEI in Europe.To understand the prevalence and practice of transition services in Europe for young people with IEI, encompassing both primary immunodeficiencies (PID) and systemic autoinflammatory disorders (AID).A survey was generated by the European Reference Network on immunodeficiency, autoinflammatory, and autoimmune diseases Transition Working Group and electronically circulated, through professional networks, to pediatric centers across Europe looking after children with IEI.Seventy-six responses were received from 52 centers, in 45 cities across 17 different countries. All services transitioned patients to adult services, mainly to specialist PID or AID centers, typically transferring up to ten patients to adult care each year. The transition process started at a median age of 16-18 years with transfer to the adult center occurring at a median age of 18-20 years. 75% of PID and 68% of AID centers held at least one joint appointment with pediatric and adult services prior to the transfer of care. Approximately 75% of PID and AID services reported having a defined transition process, but few centers reported national disease-specific transition guidelines to refer to.Transition services for children with IEI in Europe are available in many countries but lack standardized guidelines to promote best practice.
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| 6. |
- Lingman Framme, Jenny, 1977, et al.
(författare)
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Long-Term Follow-Up of Newborns with 22q11 Deletion Syndrome and Low TRECs
- 2022
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Ingår i: Journal of Clinical Immunology. - : Springer. - 0271-9142 .- 1573-2592. ; 42, s. 618-633
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Tidskriftsartikel (refereegranskat)abstract
- Background: Population-based neonatal screening using T-cell receptor excision circles (TRECs) identifies infants with profound T lymphopenia, as seen in cases of severe combined immunodeficiency, and in a subgroup of infants with 22q11 deletion syndrome (22q11DS).Purpose: To investigate the long-term prognostic value of low levels of TRECs in newborns with 22q11DS.Methods: Subjects with 22q11DS and low TRECs at birth (22q11Low, N=10), matched subjects with 22q11DS and normal TRECs (22q11Normal, N=10), and matched healthy controls (HC, N=10) were identified. At follow-up (median age 16 years), clinical and immunological characterizations, covering lymphocyte subsets, immunoglobulins, TRECs, T-cell receptor repertoires, and relative telomere length (RTL) measurements were performed.Results: At follow-up, the 22q11Low group had lower numbers of naïve T-helper cells, naïve T-regulatory cells, naïve cytotoxic T cells, and persistently lower TRECs compared to healthy controls. Receptor repertoires showed skewed V-gene usage for naïve T-helper cells, whereas for naïve cytotoxic T cells, shorter RTL and a trend towards higher clonality were found. Multivariate discriminant analysis revealed a clear distinction between the three groups and a skewing towards Th17 differentiation of T-helper cells, particularly in the 22q11Low individuals. Perturbations of B-cell subsets were found in both the 22q11Low and 22q11Normal group compared to the HC group, with larger proportions of naïve B cells and lower levels of memory B cells, including switched memory B cells.Conclusions: This long-term follow-up study shows that 22q11Low individuals have persistent immunologic aberrations and increased risk for immune dysregulation, indicating the necessity of lifelong monitoring.Clinical Implications: This study elucidates the natural history of childhood immune function in newborns with 22q11DS and low TRECs, which may facilitate the development of programs for long-term monitoring and therapeutic choices.
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| 7. |
- Lingman Framme, Jenny, 1977, et al.
(författare)
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Retrospective analysis of TREC based newborn screening results and clinical phenotypes in infants with the 22q11 deletion syndrome.
- 2014
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Ingår i: Journal of clinical immunology. - : Springer Science and Business Media LLC. - 1573-2592 .- 0271-9142. ; 34:4, s. 514-9
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Tidskriftsartikel (refereegranskat)abstract
- Population-based newborn screening using T-cell receptor excision circles (TREC) identifies infants with severe T-lymphopenia, seen in severe combined immunodeficiencies (SCID), but also infants with the 22q11 deletion syndrome (22q11DS). Methods for analysis of kappa-deleting recombination excision circles (KREC) help identifying infants with B-lymphopenia. We aimed to evaluate the occurrence of abnormal TREC or KREC newborn screening results in 22q11DS patients and assessed the clinical relevance of abnormal screening reports.
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| 8. |
- Milner, Joshua D, et al.
(författare)
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Autoimmunity in severe combined immunodeficiency (SCID): lessons from patients and experimental models.
- 2008
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Ingår i: Journal of clinical immunology. - : Springer Science and Business Media LLC. - 0271-9142 .- 1573-2592. ; 28 Suppl 1, s. S29-33
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Forskningsöversikt (refereegranskat)abstract
- Autoimmunity is observed in many immunodeficiencies and is thought to be mediated mainly by persistent infection. Severe combined immunodeficiency (SCID) is the most severe form of immunodeficiency and is also on occasion associated with autoimmune phenomena, usually in the form of the Omenn's Syndrome phenotype. Recent studies both in human and mice shed light into the pathogenesis of these two seemingly different conditions occurring together. Central tolerance, which is in charge of elimination of autoreactive T-cell clones, is defective in SCID because of markedly reduced expression of Aire, a transcriptional regulator for the expression of tissue-specific antigens in the thymus. Peripheral tolerance is also markedly decreased in SCID because of several factors including the expansion of T-cell clones as a consequence of the lymphopenia observed in these condition as well as a diminished number of T regulatory (FOXP3+)cells, allowing autoreactive T cells to proliferate and infiltrate various organs in the body of SCID. It is thus of no surprise when both central and peripheral tolerance are impaired that autoimmunity can be observed in SCID.
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