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- Andersson Svärd, Agnes, et al.
(författare)
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Decreased HLA-DQ expression on peripheral blood cells in children with varying number of beta cell autoantibodies
- 2020
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Ingår i: Journal of Translational Autoimmunity. - : Elsevier BV. - 2589-9090. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- The risk for type 1 diabetes is strongly associated with HLA-DQ and the appearance of beta cell autoantibodies against either insulin, glutamate decarboxylase (GAD65), insulinoma-associated protein-2 (IA-2), or zinc transporter 8 (ZnT8). Prolonged exposure to autoantibodies may be related to T cell exhaustion known to occur in chronic infections or autoimmune disorders. It was hypothesized that autoantibody exposure may affect HLA-DQ expression on peripheral blood cells and thereby contribute to T cell exhaustion thought to be associated with the pathogenesis of type 1 diabetes. The aim of this study was to determine whether autoantibody exposure as an expression of autoimmunity burden was related to peripheral blood cell HLA-DQ cell surface expression in either 1) a cross-sectional analysis or 2) cumulative as area under the trajectory of autoantibodies during long term follow-up in the Diabetes Prediction in Skåne (DiPiS) study. Children (n = 67), aged 10-15 years were analyzed for complete blood count, HLA-DQ cell surface median fluorescence intensity (MFI), autoantibody frequency, and HLA genotypes by Next Generation Sequencing. Decreased HLA-DQ cell surface MFI with an increasing number of autoantibodies was observed in CD16+, CD14+CD16-, CD4+ and CD8+ cells but not in CD19+ cells and neutrophils. HLA-DQ cell surface MFI was associated with HLA-DQ2/8 in CD4+ T cells, marginally in CD14+CD16- monocytes and CD8+ T cells. These associations appeared to be related to autoimmunity burden. The results suggest that HLA-DQ cell surface expression was related to HLA and autoimmunity burden.
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| 5. |
- Sjöström, Bitte, et al.
(författare)
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Increased intestinal permeability in primary Sjögren's syndrome and multiple sclerosis
- 2021
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Ingår i: Journal of Translational Autoimmunity. - : Elsevier BV. - 2589-9090. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- There is increasing evidence suggesting a role of intestinal dysfunction in a number of autoimmune diseases. Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease with a documented increased level of intestinal inflammation, whereas multiple sclerosis (MS) is an organ-specific autoimmune disease known to exhibit increased intestinal permeability. In this study we determine to what extent intestinal inflammation, analysed by a faecal calprotectin ELISA, is accompanied by altered intestinal wall permeability, as measured by a lactulose and mannitol intestinal absorption assay. Intestinal permeability was increased in both pSS and MS patients, while faecal calprotectin was elevated in pSS but normal in MS. Our findings suggest different mechanisms mediating a leaky gut in these two diseases: in pSS there is autoimmune attack directly on the intestinal wall; in MS, with autoimmunity being limited to the CNS, it may be due to a disturbed CNS regulation of enteric nerve function.
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| 6. |
- Stenberg, Pål, et al.
(författare)
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Zinc as a modulator of transglutaminase activity - Laboratory and pathophysiological aspects
- 2021
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Ingår i: Journal of Translational Autoimmunity. - : Elsevier BV. - 2589-9090. ; 4
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Forskningsöversikt (refereegranskat)abstract
- For a whole century, citrate has been used as an in vitro anticoagulant via chelation of calcium. Later, also EDTA was introduced as an anticoagulant. An often overlooked fact is that zinc is bound to citrate and EDTA with affinities much greater than that for calcium, imposing problems in biomedical research. In vivo, proteins of the S100 family are released from leukocytes and known to bind calcium. Some of them, e.g., calprotectin, also chelate zinc. Thus, at an inflamed site, the ratio between Ca2+ and Zn2+ is changed. This mechanism is of importance for the modulation of the activation of a fascinating family of post-translationally acting calcium-dependent thiol enzymes, the transglutaminases, which are inhibited by zinc. This presentation illustrates the complexity of in vitro studies with zinc. Moreover, it exemplifies the role of Zn2+ in pathophysiological situations such as celiac disease and neurodegeneration.
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| 7. |
- Thomsen, Hauke, et al.
(författare)
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Familial risks between Graves disease and Hashimoto thyroiditis and other autoimmune diseases in the population of Sweden
- 2020
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Ingår i: Journal of Translational Autoimmunity. - : Elsevier BV. - 2589-9090. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Genetic and family studies have indicated that Graves disease and Hashimoto thyroiditis have a heritable component which appears to be shared to some extend also with some other autoimmune diseases (AIDs). In the present nation-wide study we describe familial risk for Graves disease and Hashimoto thyroiditis identified from the Swedish Hospital Discharge Register (years 1964 through 2012) and the Outpatient Register (2001 through 2012). Family relationships were obtained from the Multigeneration Register and cancers from the Cancer Registry. Familial standardized incidence ratios (SIRs) were calculated for 29,005 offspring with Graves disease and for 25,607 offspring with Hashimoto thyroiditis depending on any of 43 AIDs in parents or siblings. The concordant familial risks for Graves disease and Hashimoto thyroiditis were 3.85 and 4.75, higher for men than for women. The familial risks were very high (11.35, Graves and 22.06, Hashimoto) when both a parent and a sibling were affected. Spousal familial risks were higher for Hashimoto thyroiditis (1.98/1.93) than for Graves disease (1.48/1.50). For Graves disease, 24 discordant AIDs showed a significant association; for Hashimoto thyroiditis, 20 discordant associations were significant. All significant discordant associations were positive for the two thyroid AIDs, with the exception of Hashimoto thyroiditis with Reiter disease. Overall 8 associations were significant only for Graves disease and 6 Hashimoto thyroiditis. The overall high concordant familial risks for Graves disease and Hashimoto thyroiditis suggest a strong genetic contribution to the familial risk. Significant familial associations among more than half of the 43 AIDs attest to the extensive polyautoimmunity among thyroid AIDs.
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| 8. |
- Van Hoovels, Lieve, et al.
(författare)
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Impact of autoimmune serology test results on RA classification and diagnosis
- 2022
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Ingår i: Journal of Translational Autoimmunity. - : Elsevier. - 2589-9090. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis (RA) is the most common systemic autoimmune disease and also the most severe arthritic disorder. The measurement of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) in serum supports the diagnosis of RA, which gained increasing significance over the last 65 years. However, a high variability between RF and ACPA methods has been described, impacting the diagnostic performance of the current ACR/EULAR RA classification criteria. The great number of commercially available assays, often lacking traceability to an international standard, is a major factor attributing to this in-between assay variability. The adoption of an international standard for ACPA, as is since long available for rheumatoid factor, is therefore highly desirable. Further harmonization in clinical interpretation of RF/ACPA assays could be obtained by harmonization of the cut-offs, for both the low and high antibody levels, based on predefined specificity in disease controls. Reporting test result specific likelihood ratios (LR) adds value in the interpretation of autoantibody tests. However, a good understanding of the control population used to define antibody test result interval-associated LRs is crucial in defining the diagnostic performance characteristics of antibody serology. Finally, specificity in RA classification can be improved by refining serological weight scoring taking into account the nature of the antibody, the antibody level and double RF + ACPA positivity.
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