| 1. |
- Alexander, Lind, et al.
(författare)
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Antibody detection by agglutination-PCR (ADAP) assays for the analysis of tissue transglutaminase autoantibodies in celiac disease
- 2023
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Ingår i: Journal of Immunological Methods. - 0022-1759. ; 518
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims: Tissue transglutaminase autoantibodies (tTGA) are used as diagnostic markers of celiac disease. Different methods have been developed for the detection of tTGA of which enzyme-linked immunosorbent assays (ELISA), radiobinding assays (RBA) and electrochemiluminescence (ECL) assays are the most commonly used. Here we aimed to evaluate a novel antibody detection by agglutination-PCR (ADAP) assay for the detection of tTGA. Methods: Included were 126 children with untreated celiac disease (UCD), 64 disease controls (DC), 21 children with potential celiac disease (PCD), and 1501 children from the general population. Tissue TGA were determined using an automated ADAP assay platform and compared with two RBAs for the detection of IgA-tTG and IgG-tTG, respectively. Results: ADAP detected tTGA in 123/126 (97.6%) UCD children compared with 122/126 (96.8%) using RBA-IgA-tTG and RBA-IgG-tTG (p > 0.9999), respectively. Among DC, ADAP detected 5/64 (7.8%) children with tTGA compared with 4/64 (6.3%) with RBA-IgA-tTG (p > 0.9999) and 8/64 (12.5%) with RBA-IgG-tTG (p = 0.5600), respectively. Tissue TGAs were equally detected in children with PCD in both assays. In the general population, 4/1501 (0.3%) were tTGA positive using ADAP compared with 3/1501 (0.2%) for RBA-IgA-tTG and RBA-IgG-tTG (p > 0.9999), respectively. The area under the curves (AUCs) were 0.998 for ADAP, 0.994 for RBA-IgA-tTG, and 0.999 for RBA-IgG-tTG, respectively. Conclusions: No difference in specificity and sensitivity of tTGA for the diagnosis of celiac disease was reported between ADAP and RBA. ADAP could be recommended as the first-line screening method of larger populations for celiac disease.
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| 2. |
- Bennet, Christian, 1954, et al.
(författare)
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Never trust an unsound theory
- 2022
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Ingår i: Theoria. - : Wiley. - 0040-5825 .- 1755-2567. ; 88:5, s. 1053-1056
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Tidskriftsartikel (refereegranskat)abstract
- Lajevardi and Salehi, in “There may be many arithmetical Gödel sentences”, argue against the use of the definite article in the expression “the Gödel sentence”, by claiming that any unsound theory has Gödelian sentences with different truth values. We show that their Theorems 1 and 2 are special cases (modulo Löb's theorem and the first incompleteness theorem) of general observations pertaining to fixed points of any formula, and argue that the false sentences of Lajevardi and Salehi are in fact not Gödel sentences.
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| 3. |
- Jahoor, Farook, et al.
(författare)
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Metabolomics Profiling of Patients With A-β+ Ketosis-Prone Diabetes During Diabetic Ketoacidosis
- 2021
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 70:8, s. 1898-1909
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Tidskriftsartikel (refereegranskat)abstract
- When stable and near-normoglycemic, patients with "A-β+" ketosis-prone diabetes (KPD) manifest accelerated leucine catabolism and blunted ketone oxidation, which may underlie their proclivity to develop diabetic ketoacidosis (DKA). To understand metabolic derangements in A-β+ KPD patients during DKA, we compared serum metabolomics profiles of adults during acute hyperglycemic crises, without (n = 21) or with (n = 74) DKA, and healthy control subjects (n = 17). Based on 65 kDa GAD islet autoantibody status, C-peptide, and clinical features, 53 DKA patients were categorized as having KPD and 21 type 1 diabetes (T1D); 21 nonketotic patients were categorized as having type 2 diabetes (T2D). Patients with KPD and patients with T1D had higher counterregulatory hormones and lower insulin-to-glucagon ratio than patients with T2D and control subjects. Compared with patients withT2D and control subjects, patients with KPD and patients with T1D had lower free carnitine and higher long-chain acylcarnitines and acetylcarnitine (C2) but lower palmitoylcarnitine (C16)-to-C2 ratio; a positive relationship between C16 and C2 but negative relationship between carnitine and β-hydroxybutyrate (BOHB); higher branched-chain amino acids (BCAAs) and their ketoacids but lower ketoisocaproate (KIC)-to-Leu, ketomethylvalerate (KMV)-to-Ile, ketoisovalerate (KIV)-to-Val, isovalerylcarnitine-to-KIC+KMV, propionylcarnitine-to-KIV+KMV, KIC+KMV-to-C2, and KIC-to-BOHB ratios; and lower glutamate and 3-methylhistidine. These data suggest that during DKA, patients with KPD resemble patients with T1D in having impaired BCAA catabolism and accelerated fatty acid flux to ketones-a reversal of their distinctive BCAA metabolic defect when stable. The natural history of A-β+ KPD is marked by chronic but varying dysregulation of BCAA metabolism.
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| 4. |
- Lind, Alexander, et al.
(författare)
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Multiplex agglutination-PCR (ADAP) autoantibody assays compared to radiobinding autoantibodies in type 1 diabetes and celiac disease
- 2022
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Ingår i: Journal of Immunological Methods. - : Elsevier BV. - 1872-7905 .- 0022-1759. ; 506
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Tidskriftsartikel (refereegranskat)abstract
- Multiplex Antibody-Detection by Agglutination-PCR (ADAP) assay was compared to singleplex standard radiobinding assays (RBA) to detect autoantibodies against insulin (IAA), GAD65 (GADA), islet antigen-2 (IA-2A), ZnT8 (ZnT8A) and tissue transglutaminase (TGA). Serum samples from 272 (114F/158M), 15-73 years of age healthy controls and 227 (109F/118M) newly diagnosed type 1 diabetes children, 1-11 years of age, were analyzed in both assay systems.The original WHO standard 97/550 and in-house reference standards for RBA were compared to ADAP. The ADAP and RBA generated parallel reference standards in all assays except TGA. Lower detection limits were observed in the ADAP assay for GADA,IAA and ZnT8A, markedly for TGA, but not for IA-2A. The Receiver Operating Characteristics (ROC) curve AUC analyses for pairwise comparison of ADAP with RBA showed no difference for GADA (n.s.), ADAP greater AUC for IAA (p = 0.005), RBA greater AUC for IA-2A (p = 0.0004) and ZnT8A (p < 0.0001) while ADAP TGA had a greater AUC compared to both RBA TGA-IgG (p < 0.0001) and TGA-IgA (p < 0.0001) . These data suggest that the ADAP and RBA assays are comparable with equal performance for GADA, better ADAP performance for IAA while the RBA showed better performance in both IA-2A and ZnT8A associated with greater heterogeneity in autoantibody levels. The simultaneous analysis of 5 different autoantibodies by ADAP in sample volume reduced to only 4 μL and at an increased lower detection limit in all assays except IA-2A makes the ADAP automated autoantibody assay a distinct advantage for high throughput screening.
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| 5. |
- Salami, Falastin, et al.
(författare)
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Long-Term GAD-alum Treatment Effect on Different T-Cell Subpopulations in Healthy Children Positive for Multiple Beta Cell Autoantibodies
- 2022
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Ingår i: Journal of Immunology Research. - : Hindawi Limited. - 2314-7156 .- 2314-8861. ; 2022
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The objective of this study was to explore whether recombinant GAD65 conjugated hydroxide (GAD-alum) treatment affected peripheral blood T-cell subpopulations in healthy children with multiple beta cell autoantibodies. Method. The Diabetes Prevention–Immune Tolerance 2 (DiAPREV-IT 2) clinical trial enrolled 26 children between 4 and 13 years of age, positive for glutamic acid decarboxylase autoantibody (GADA) and at least one other autoantibody (insulin, insulinoma antigen-2, or zinc transporter 8 autoantibody (IAA, IA-2A, or ZnT8A)) at baseline. The children were randomized to two doses of subcutaneously administered GAD-alum treatment or placebo, 30 days apart. Complete blood count (CBC) and immunophenotyping of T-cell subpopulations by flow cytometry were performed regularly during the 24 months of follow-up posttreatment. Cross-sectional analyses were performed comparing lymphocyte and T-cell subpopulations between GAD-alum and placebo-treated subjects. Results. GAD-alum-treated children had lower levels of lymphocytes (109 cells/L) (), T-cells (103 cells/μL) (), T-helper cells (103 cells/μL) (), and cytotoxic T-cells (103 cells/μL) () compared to the placebo-treated children 18 months from first GAD-alum injection. This difference remained 24 months after the first treatment for lymphocytes (), T-cells (), T-helper cells (), and cytotoxic T-cells (). Conclusion. Our findings suggest that levels of total T-cells and T-cell subpopulations declined 18 and 24 months after GAD-alum treatment in healthy children with multiple beta-cell autoantibodies including GADA.
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