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- Fryk, Emanuel, et al.
(författare)
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Galectin-1 correlates with inflammatory markers and T regulatory cells in children with type 1 diabetes and/or celiac disease
- 2024
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press. - 1365-2249 .- 0009-9104. ; 215:3, s. 240-250
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes (T1D) and celiac disease (CeD) are common autoimmune diseases in children where the pathophysiology is not fully characterized. The autoimmune process involves a complex scenario of both inflammatory and regulatory features. Galectin-1 (GAL-1) has a wide range of biological activities e.g. interaction with immune cells. We examined the relationship between GAL-1 and soluble immune markers and T-cell subsets in a cohort of children with T1D and/or CeD relative to healthy children. GAL-1, together with several soluble immune markers [e.g. interleukins (IL)], tumor necrosis factor (TNF), acute phase proteins, and matrix metalloproteinases (MMP) were measured in sera from children with T1D and/or CeD by fluorochrome (Luminex) technique using children without these diseases as a reference. Subgroups of T cells, including T-regulatory (Treg) cells, were analysed by flow cytometry. Association between GAL-1, pro-inflammatory markers, and Treg cells differed depending on which illness combination was present. In children with both T1D and CeD, GAL-1 correlated positively with pro-inflammatory markers (IL-1 beta, IL-6, and TNF-alpha). Composite scores increased the strength of correlation between GAL-1 and pro-inflammatory markers, Th1-associated interferon (IFN)-gamma, and T1D-associated visfatin. Contrary, in children diagnosed with exclusively T1D, GAL-1 was positively correlated to CD25hi and CD25hiCD101+ Treg cells. For children with only CeD, no association between GAL-1 and other immune markers was observed. In conclusion, the association observed between GAL-1, soluble immune markers, and Treg cells may indicate a role for GAL-1 in the pathophysiology of T1D and, to some extent, also in CeD. Type 1 diabetes (T1D) and celiac disease (CeD) are common autoimmune diseases in children where pathophysiology is not fully characterized. The autoimmune process involves a complex scenario of both inflammatory and regulatory features. Galectin-1 (GAL-1) has a wide range of biological activities e.g. interaction with immune cells and the association observed between GAL-1, soluble immune markers, and T regulatory (Treg) cells may indicate a role for GAL-1 in the pathophysiology of children with T1D and, to some extent, also in children with CeD. Graphical Abstract
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- Ross, Owen A., et al.
(författare)
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Mitochondrial DNA damage in lymphocytes : a role in immunosenescence?
- 2002
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Ingår i: Experimental Gerontology. - : Elsevier. - 0531-5565 .- 1873-6815. ; 37:2-3, s. 329-340
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Tidskriftsartikel (refereegranskat)abstract
- An age-related increase of DNA damage/mutation has been previously reported in human lymphocytes. The high copy number and mutation rate make the mtDNA genome an ideal candidate for assessing damage and to act as a potential biomarker of ageing. In the present study, two assays were developed to evaluate the level of mtDNA4977 and the accumulation of point mutations with age. A competitive polymerase chain reaction (PCR) methodology incorporating three primers was used to detect and quantify the levels of mtDNA4977 and a novel heteroduplex reference strand conformational analysis (RSCA) technique was used to analyse the accumulation of point mutations. The assays were applied to an in vitro model of T cell ageing and ex vivo DNA samples from an elderly cohort of subjects and a younger control group. The mtDNA4977 was detected in all the DNA samples examined but only a very low concentration was observed and no age-related increase or accumulation was observed. No accumulation of point mutations was identified using RSCA within the T cell clones as they were aged or the ex vivo lymphocytes from the elderly cohort. A higher level of variation was observed within the ex vivo DNA samples, verifying the high resolution of RSCA and its ability to identify different mtDNA species, although no correlation with age was observed. The low level of mtDNA damage observed with respect to the ex vivo lymphocyte DNA samples within this study may be due in part to the high turnover of blood cells/mtDNA, which may inhibit the accumulation of genetically abnormal mtDNA that may play a role in immunosenescence. A similar explanation may also apply to the in vitro model of T cell ageing if the vast majority of the cells are replicating rather than entering senescence.
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- Tompa, Andrea
(författare)
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Pinpointing biomarkers of importance for children with combined type 1 diabetes and celiac disease
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Type 1 diabetes (T1D) and celiac disease are both characterized by an autoimmune feature. The diseases also share the same risk genes, and thereby patients have an increased risk of developing the other disease subsequently. The pattern of peripheral T and B cell subsets and soluble immune markers (cytokines, chemokines, acute phase proteins, adipocytokines and matrix metalloproteinases) are not yet well characterized in children with a combination of the common pediatric immunological disorders, T1D and celiac disease. To better understand the complex pathophysiology, it is important to gain a deeper knowledge of alterations present in the peripheral immune profile in children with these autoimmune diseases. Pinpointing biomarkers, e.g. peripheral immune markers, can hopefully contribute to the improvement of prognosis, diagnosis, and disease management. Flow cytometry is useful for studying different immune cells, but several pre-analytical factors may affect the outcome. In order to generate reliable results, it is important to evaluate the impact of different pre-analytical factors that possibly can lead to in vitro alterations of the immune cells.Aim: The overall aim of this thesis was to increase our knowledge of peripheral immune marker patterns in children with a combined diagnosis of T1D and celiac disease, with a focus on T and B cell subsets and soluble immune markers; by immunological methods evaluated and adapted for this purpose.Methods: This thesis comprises methodological and cross-sectional studies. The methodological studies are based on whole blood collected from sixty blood donors to examine the impact of pre-analytical factors (anticoagulant, sample handling time, isolation and cryopreservation) that may affect the immune cells (Study I, II). The cross-sectional studies include blood samples collected from a total of 103 participants (children with T1D and/or celiac disease or no diagnosis at all). The pattern of peripheral B (Study II) and T (Study III) cell subsets were examined by flow cytometry. Nearly thirty soluble immune markers were quantified in serum by Luminex technology (Study IV).Results: Peripheral lymphocytes were stable in whole blood samples up to 24 hours, regardless of the anticoagulant. Generally, T and B cell subsets were not affected by isolation and cryopreservation. Children with combined T1D and celiac disease had higher percentages of terminally differentiated memory T helper cells, lower percentages of effector memory T cytotoxic cells and lower expression of suppressive immune markers on regulatory T cells compared with the other study groups. Further, children with combined T1D and celiac disease had a higher percentage of memory B and lower percentages of naive B cells than children with either T1D or celiac disease. Contrary, children with single diagnoses had an inverted naive/memory B cell pattern compared to children with combined diagnoses. Several of the "classical" (cytokines, chemokines), as well as "non-classical" (acute phase proteins, adipocytokines, matrix metalloproteinases) immune markers, were lower in children with combined diagnoses compared to the other study groups.Conclusions: Based on our results, we conclude that whole blood samples stored up to 24 hours are feasible for flow cytometric analysis of lymphocyte subsets, regardless of the type of anticoagulant. Further, isolated and cryopreserved immune cells are feasible for flow cytometric analysis of T and B cell subsets. Impairment in the T and B cells mediated immune regulation in children with combined T1D and celiac disease seems to be clearly divergent from those seen in children with exclusively one of these two autoimmune diseases. Children with combined T1D and celiac disease appear to have a suppressed immune profile, including "classical" and "non-classical" immune markers. The methodological studies provide deeper knowledge of how reliable results can be obtained in studies of peripheral immune cells, e.g., in children with autoimmune diseases. The knowledge obtained by this thesis also brings a better understanding of the pattern of peripheral immune markers in T1D and/or celiac disease. This could potentially contribute to promoting the improvement of prognosis, diagnosis, and disease management.
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- Tompa, Andrea, 1969, et al.
(författare)
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Shift in the B cell subsets between children with type 1 diabetes and/or celiac disease
- 2024
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press. - 1365-2249 .- 0009-9104. ; 216:1, s. 36-44
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Tidskriftsartikel (refereegranskat)abstract
- Our purpose was to characterize the pattern of B cell subsets in children with a combined diagnosis of type 1 diabetes (T1D) and celiac disease (C) since children with single or double diagnosis of these autoimmune diseases may differ in peripheral B cell subset phenotype patterns. B cells were analyzed with flow cytometry for the expression of differentiation/maturation markers to identify transitional, naive, and memory B cells. Transitional (CD24(hi)CD38(hi)CD19(+)) and memory Bregs (mBregs; CD24(hi)CD27(+)CD19(+), CD1d(+)CD27(+)CD19(+), and CD5(+)CD1d(+)CD19(+)) were classified as B cells with regulatory capacity. Children with a combined diagnosis of T1D and C showed a pattern of diminished peripheral B cell subsets. The B cells compartment in children with combined diagnosis had higher percentages of memory B subsets and Bregs, including activated subsets, compared to children with either T1D or C. Children with combined diagnosis had a lower percentage of naive B cells (CD27(-)CD19(+); IgD(+)CD19(+)) and an increased percentage of memory B cells (CD27(+)CD19(+); IgD(-)CD19(+)). A similar alteration was seen among the CD39(+) expressing naive and memory B cells. Memory Bregs (CD1d(+)CD27(+)CD19(+)) were more frequent, contrary to the lower percentage of CD5(+) transitional Bregs in children with a combined diagnosis. In children with either T1D or C, the peripheral B cell compartment was dominated by naive cells. Differences in the pattern of heterogeneous peripheral B cell repertoire subsets reflect a shifting in the B cell compartment between children with T1D and/or C. This is an immunological challenge of impact on the pathophysiology of these autoimmune diseases. A larger compartment of naive B and Breg subsets, including activated subsets, and smaller compartment of the memory B and Breg subsets are seen in children with isolated type 1 diabetes (T1D) or celiac disease (C). In children with the combined diagnosis, a shifting of the naive B subset compartment toward a more mature/differentiated B cell compartment was observed, indicating another type of disturbance of the B cell mediated immune regulation compared to what is present in the context of only one isolated autoimmune disease. Differences in the pattern of heterogeneous peripheral B cell repertoire subsets reflect a shifting in the B cell compartment between children with T1D and/or C.
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