| 1. |
- Andersson, C, et al.
(författare)
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The three ZNT8 autoantibody variants together improve the diagnostic sensitivity of childhood and adolescent type 1 diabetes
- 2011
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Ingår i: Autoimmunity. - : Taylor & Francis. - 0891-6934 .- 1607-842X. ; 44:5, s. 394-405
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Tidskriftsartikel (refereegranskat)abstract
- Aims: We tested whether autoantibodies to all three ZnT8RWQ variants, GAD65, insulinoma-associated protein 2 (IA-2), insulin and autoantibodies to islet cell cytoplasm (ICA) in combination with human leukocyte antigen (HLA) would improve the diagnostic sensitivity of childhood type 1 diabetes by detecting the children who otherwise would have been autoantibody-negative.Methods: A total of 686 patients diagnosed in 1996–2005 in Skåne were analyzed for all the seven autoantibodies [arginin 325 zinc transporter 8 autoantibody (ZnT8RA), tryptophan 325 zinc transporter 8 autoantibody (ZnT8WA), glutamine 325 Zinc transporter 8 autoantibody (ZnT8QA), autoantibodies to glutamic acid decarboxylase (GADA), Autoantibodies to islet-antigen-2 (IA-2A), insulin autoantibodies (IAA) and ICA] in addition to HLA-DQ genotypes.Results: Zinc transporter 8 autoantibody to either one or all three amino acid variants at position 325 (ZnT8RWQA) was found in 65% (449/686) of the patients. The frequency was independent of age at diagnosis. The ZnT8RWQA reduced the frequency of autoantibody-negative patients from 7.5 to 5.4%—a reduction by 28%. Only 2 of 108 (2%) patients who are below 5 years of age had no autoantibody at diagnosis. Diagnosis without any islet autoantibody increased with increasing age at onset. DQA1-B1*X-0604 was associated with both ZnT8RA (p = 0.002) and ZnT8WA (p = 0.01) but not with ZnT8QA (p = 0.07). Kappa agreement analysis showed moderate (>0.40) to fair (>0.20) agreement between pairs of autoantibodies for all combinations of GADA, IA-2A, ZnT8RWQA and ICA but only slight ( < 0.19) agreement for any combination with IAA.Conclusions: This study revealed that (1) the ZnT8RWQA was common, independent of age; (2) multiple autoantibodies were common among the young; (3) DQA1-B1*X-0604 increased the risk for ZnT8RA and ZnT8WA; (4) agreement between autoantibody pairs was common for all combinations except IAA. These results suggest that ZnT8RWQA is a necessary complement to the classification and prediction of childhood type 1 diabetes as well as to randomize the subjects in the prevention and intervention of clinical trials.
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| 2. |
- Kanatsuna, N, et al.
(författare)
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Doubly reactive INS-IGF2 autoantibodies in children with newly diagnosed autoimmune (type 1) diabetes
- 2015
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Ingår i: Scandinavian Journal of Immunology. - : Wiley-Blackwell. - 0300-9475 .- 1365-3083. ; 82:4, s. 361-369
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Tidskriftsartikel (refereegranskat)abstract
- The splice variant INS-IGF2 entails the preproinsulin signal peptide, the insulin B-chain, eight amino acids of the C-peptide and 138 unique amino acids from an ORF in the IGF2 gene. The aim of this study was to determine whether levels of specific INS-IGF2 autoantibodies (INS-IGF2A) were related to age at diagnosis, islet autoantibodies, HLA-DQ or both, in patients and controls with newly diagnosed type 1 diabetes. Patients (n = 676), 0-18 years of age, diagnosed with type 1 diabetes in 1996-2005 and controls (n = 363) were analysed for specific INS-IGF2A after displacement with both cold insulin and INS-IGF2 to correct for non-specific binding and identify double reactive sera. GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, ZnT8QA and HLA-DQ genotypes were also determined. The median level of specific INS-IGF2A was higher in patients than in controls (P < 0.001). Irrespective of age at diagnosis, 19% (126/676) of the patients had INS-IGF2A when the cut-off was the 95th percentile of the controls (P < 0.001). The risk of INS-IGF2A was increased among HLA-DQ2/8 (OR = 1.509; 95th CI 1.011, 2.252; P = 0.045) but not in 2/2, 2/X, 8/8, 8/X or X/X (X is neither 2 nor 8) patients. The association with HLA-DQ2/8 suggests that this autoantigen may be presented on HLA-DQ trans-heterodimers, rather than cis-heterodimers. Autoantibodies reactive with both insulin and INS-IGF2A at diagnosis support the notion that INS-IGF2 autoimmunity contributes to type 1 diabetes.
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| 3. |
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| 4. |
- Kårehed, Karin, et al.
(författare)
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Fibrinogen and histidine-rich glycoprotein in early-onset preeclampsia
- 2010
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 89:1, s. 131-139
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether plasma levels of fibrinogen and the placental tissue distributions of fibrinogen and histidine-rich glycoprotein (HRG) differ between early- and late-onset preeclampsia. DESIGN: The study comprised 18 women with early-onset (gestational weeks 24-32) and 19 women with late-onset (gestational weeks 35-42) preeclampsia. As controls concerning the plasma levels of fibrinogen, we used samples from non-pregnant fertile women, healthy pregnant women at gestational weeks 24-32 and healthy pregnant women at gestational weeks 35-42. Placental samples from women with healthy pregnancies at gestational weeks 35-42 served as controls in the immunohistochemical staining. SETTING: Uppsala University Hospital, Uppsala. METHODS: Plasma fibrinogen levels were analyzed and the placental tissue expression of fibrinogen and HRG determined by immunohistochemistry. RESULTS: Plasma level of fibrinogen was increased in early-onset, but not late-onset, preeclampsia. Levels of fibrinogen were significantly lower, and that of HRG significantly higher, in placentas from women with early-onset preeclampsia as compared with control placentas (p = 0.01 and 0.001). CONCLUSIONS: HRG and fibrinogen might be involved in the hypercoagulability and the angiogenic imbalance seen in early-onset preeclampsia.
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| 5. |
- Lundqvist, Pia, et al.
(författare)
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Development and psychometric properties of the Swedish ALPS-Neo pain and stress assessment scale for newborn infants
- 2014
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Ingår i: Acta Paediatrica. - : Wiley-Blackwell. - 0803-5253 .- 1651-2227. ; 103:8, s. 833-839
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To validate and evaluate the psychometric properties of the ALPS-Neo, a new pain assessment scale created for the continuous evaluation of pain and stress in preterm and sick term infants.METHODS: A unidimensional scale for continuous pain, Astrid Lindgren Children's Hospital Pain Scale (ALPS 1), was developed further to assess continuous pain and stress in infants treated in the neonatal intensive care unit (NICU). The pain scale includes observations of five behaviours. A manual was created, clarifying the scoring criteria. An internal and an external panel assessed face validity. Psychometric properties were evaluated in three different steps. Inter-rater reliability was estimated from video-based assessments (n = 625) using weighted kappa statistics (test I). Inter-rater reliability was further evaluated in test II (n = 125) and test III (n = 96) by real-time assessments using the intraclass correlation coefficient (ICC) and Cronbach's alpha.RESULTS: The final inter-rater reliability (test III) was assessed as good with ICC 0.91 for the total score and 0.62-0.81 for the five items. Cronbach's alpha showed 0.95 for the total score.CONCLUSION: ALPS-Neo is a new assessment tool for optimising the management of pain and stress in newborn infants in the NICU. It has proved easy to implement and user-friendly, permitting fast, reliable observations with high inter-rater reliability.
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| 6. |
- Nilsson, Anna-Lena, et al.
(författare)
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Relationship between Ljungan virus antibodies, HLA-DQ8, and insulin autoantibodies in newly diagnosed type 1 diabetes children
- 2013
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Ingår i: Viral immunology. - : Mary Ann Liebert, Inc.. - 0882-8245 .- 1557-8976. ; 26:3, s. 207-215
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Tidskriftsartikel (refereegranskat)abstract
- Environmental factors, including viral infections, may explain an increasing and fluctuating incidence of childhood type 1 diabetes (T1D). Ljungan virus (LV) isolated from bank voles have been implicated, but it is unclear whether LV contributes to islet autoimmunity, progression to clinical onset, or both, of T1D. The aim was to test whether LV antibodies (LVAb) were related to HLA-DQ and islet autoantibodies in newly diagnosed T1D patients (n = 676) and controls (n = 309). Patients, 0-18 years of age, diagnosed with T1D in 1996-2005 were analyzed for LVAb, HLA-DQ genotypes, and all seven known islet autoantibodies (GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, and ZnT8QA). LVAb at 75th percentile, defined as cut off, was 90 (range 6-3936) U/mL and 4th quartile LVAb were found in 25% (170/676) of which 64% were < 10 (n = 108, p < 0.0001), and 27% were < 5 (n = 45; p < 0.0001) years old. The 4th quartile LVAb in children < 10 years of age correlated to HLA DQ2/8, 8/8, and 8/X (p < 0.0001). Furthermore, in the group with 4th quartile LVAb, 55% were IAA positive (p = 0.01) and correlation was found between 4th quartile LVAb and IAA in children < 10 years of age (p = 0.035). It is concluded that 1) LVAb were common among the young T1D patients and LVAb levels were higher in the younger age groups; 2) 4th quartile LVAb correlated with IAA; and 3) there was a correlation between 4th quartile LVAb and HLA-DQ8, particularly in the young patients. The presence of LVAb supports the notion that prior exposure to LV may be associated with T1D.
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| 7. |
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| 8. |
- Akhter, Tansim, 1967-, et al.
(författare)
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Artery Wall Layer Dimensions during Normal Pregnancy : A longitudinal study using non-invasive high-frequency ultrasound
- 2013
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Ingår i: American Journal of Physiology. Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 304:2, s. H229-H234
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Tidskriftsartikel (refereegranskat)abstract
- The vascular effects of normal pregnancy were investigated by estimating the intima and media thicknesses of the common carotid artery separately using 22MHz ultrasound (Collagenoson, Meudt, Germany) in 57 healthy women with normal pregnancies and pregnancy outcomes, in all three trimesters and at one year postpartum. A thick intima, thin media and high intima/media (I/M) ratio are signs of a less healthy artery wall. The mean artery wall layer dimensions remained fairly constant during pregnancy but the intima thickness and I/M thickness ratio appeared to improve (decrease) postpartum (p<0.001 for both). The cardiovascular risk parameters age, body mass index (BMI), and blood pressure in the first trimester were associated with higher I/M ratios, especially in the second trimester, whereas higher serum estradiol levels were significantly associated with a lower I/M ratio. Changes from the first to second trimesters in I/M ratio, taking into account differential changes in intima and media thickness, were significantly (p<0.05-0.001) associated with all risk parameters tested except age, which was associated with increased intima thickness (p=0.02). Associations with third trimester values and changes from first to third trimesters were similar but less apparent. Thus, fairly constant mean artery wall layer dimensions during pregnancy appeared to improve postpartum. However, higher age, BMI or blood pressure, and lower serum estradiol levels in the first trimester appeared to negatively affect the artery wall, strongly suggesting that pregnancy has negative vascular effects in some women. A less likely explanation involves possible adaptation to physiological changes during and after pregnancy.
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| 9. |
- Akhter, Tansim, 1967-, et al.
(författare)
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Association between angiogenic factors and signs of arterial aging in women with pre-eclampsia
- 2017
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Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 50, s. 93-99
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Pre-eclampsia (PE) is associated with an increased risk of cardiovascular disease (CVD) later in life. In PE there is a substantial increase in levels of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt1) and decreased levels of the pro-angiogenic factor placental growth factor (PlGF). Elevated levels of sFlt1 are also found in individuals with CVD. The aims of this study were to assess sFlt1, PlGF and the sFlt1/PlGF ratio and their correlation with signs of arterial aging by measuring common carotid artery (CCA) intima and media thicknesses and their ratio (I/M ratio) in women with and without PE.METHODS: Serum sFlt1 and PlGF levels were measured using commercially available enzyme-linked immunosorbent assay kits, and CCA intima and media thicknesses were estimated using high-frequency (22 MHz) ultrasonography in 55 women at PE diagnosis and 64 women with normal pregnancies at a similar gestational age, with reassessment one year postpartum. A thick intima, thin media and a high I/M ratio indicate a less healthy arterial wall.RESULTS: During pregnancy, higher levels of sFlt1, lower levels of PlGF and thicker intima, thinner media and higher I/M ratios were found in women with PE vs. controls (all p < 0.0001). Further, sFlt1 and the sFlt1/PlGF ratio were positively correlated with intima thickness and I/M ratio (all p < 0.0001), but negatively correlated with media thickness (p = 0.002 and 0.03, respectively). About one year postpartum, levels of sFlt1 and the sFlt1/PlGF ratio had decreased in both groups, but compared with controls women in the PE group still had higher levels (p = 0.001 and 0.02, respectively). Further, sFlt1 levels and the sFlt1/PlGF ratio were still positively correlated with intima thickness and I/M ratio.CONCLUSIONS: Higher sFlt1 levels and sFlt1/PlGF ratios in women with PE were positively associated with signs of arterial aging during pregnancy. About one year postpartum sFlt1 levels and the sFlt1/PlGF ratios were still higher in the PE group, and also associated with the degree of arterial aging.
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| 10. |
- Akhter, Tansim, 1967-, et al.
(författare)
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Serum Pentraxin 3 is associated with signs of arterial alteration in women with preeclampsia.
- 2017
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 241, s. 417-422
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Preeclampsia (PE) in pregnancy is a state of exaggerated inflammation and is associated with an increased risk of cardiovascular disease (CVD) later in life. Levels of pentraxin 3 (PTX3), a novel inflammation marker, are increased during PE and in individuals with CVD. The primary aim of this study was to assess whether serum PTX3 in women with PE is associated with adverse arterial effects; a thicker intima and higher intima/media (I/M) ratio in the common carotid artery (CCA).METHODS: Serum PTX3 levels were measured using commercially available enzyme-linked immunosorbent assay kits, and individual CCA intima and media thicknesses were estimated by 22MHz non-invasive ultrasound in 55 women at PE diagnosis and 64 women with normal pregnancies at a similar gestational age, and about one year postpartum. A thick intima, thin media and high I/M ratio indicate a less healthy artery wall.RESULTS: During pregnancy serum PTX3 correlated positively with intima thickness and I/M ratio but negatively with media thickness (all p<0.0001), indicating adverse arterial effects. About one year postpartum, PTX3 levels had decreased in both groups and there remained no significant group difference or significant correlation with CCA wall layers.CONCLUSIONS: Higher levels of serum PTX3 in women with PE were significantly associated with signs of adverse arterial effects during pregnancy, but not one year postpartum, supporting the rapid dynamics of PTX3.
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