| 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. |
- 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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| 4. |
- Andersson, Cecilia K, et al.
(författare)
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Glucose tolerance and beta-cell function in islet autoantibody-positive children recruited to a secondary prevention study.
- 2013
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 14:5, s. 341-349
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Children with type 1 diabetes (T1D) risk and islet autoantibodies are recruited to a secondary prevention study. The aims were to determine metabolic control in relation to human leukocyte antigen (HLA) genetic risk and islet autoantibodies in prepubertal children. METHODS: In 47 healthy children with GADA and at least one additional islet autoantibody, intravenous glucose tolerance test (IvGTT) and oral glucose tolerance test (OGTT) were performed 8-65 d apart. Hemoglobin A1c, plasma glucose as well as serum insulin and C-peptide were determined at fasting and during IvGTT and OGTT. RESULTS: All children aged median 5.1 (4.0-9.2) yr had autoantibodies to two to six of the beta-cell antigens GAD65, insulin, IA-2, and the three amino acid position 325 variants of the ZnT8 transporter. In total, 20/47 children showed impaired glucose metabolism. Decreased (≤30 μU/mL insulin) first-phase insulin response (FPIR) was found in 14/20 children while 11/20 had impaired glucose tolerance in the OGTT. Five children had both impaired glucose tolerance and FPIR ≤30 μU/mL insulin. Number and levels of autoantibodies were not associated with glucose metabolism, except for an increased frequency (p = 0.03) and level (p = 0.01) of ZnT8QA in children with impaired glucose metabolism. Among the children with impaired glucose metabolism, 13/20 had HLA-DQ2/8, compared to 9/27 of the children with normal glucose metabolism (p = 0.03). CONCLUSION: Secondary prevention studies in children with islet autoantibodies are complicated by variability in baseline glucose metabolism. Evaluation of metabolic control with both IvGTT and OGTT is critical and should be taken into account before randomization. All currently available autoantibody tests should be analyzed, including ZnT8QA.
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| 5. |
- Andersson, Cecilia K, 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
-
Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 44, 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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| 6. |
- Axell, Erik, et al.
(författare)
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On the Optimal K-term Approximation of a Sparse Parameter Vector MMSE Estimate
- 2009
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Ingår i: Proceedings of the 2009 IEEE Workshop on Statistical Signal Processing (SSP'09). - : IEEE. - 9781424427093 ; , s. 245-248
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Konferensbidrag (refereegranskat)abstract
- This paper considers approximations of marginalization sums thatarise in Bayesian inference problems. Optimal approximations ofsuch marginalization sums, using a fixed number of terms, are analyzedfor a simple model. The model under study is motivated byrecent studies of linear regression problems with sparse parametervectors, and of the problem of discriminating signal-plus-noise samplesfrom noise-only samples. It is shown that for the model understudy, if only one term is retained in the marginalization sum, thenthis term should be the one with the largest a posteriori probability.By contrast, if more than one (but not all) terms are to be retained,then these should generally not be the ones corresponding tothe components with largest a posteriori probabilities.
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| 7. |
- Axell, Erik
(författare)
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Spectrum Sensing Algorithms Based on Second-Order Statistics
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cognitive radio is a new concept of reusing spectrum in an opportunistic manner. Cognitive radio is motivated by recent measurements of spectrum utilization, showing unused resources in frequency, time and space. Introducing cognitive radios in a primary network inevitably creates increased interference to the primary users. Secondary users must sense the spectrum and detect primary users' signals at very low SNR, to avoid causing too much interference.This dissertation studies this detection problem, known as spectrum sensing.The fundamental problem of spectrum sensing is to discriminate an observation that contains only noise from an observation that contains a very weak signal embedded in noise. In this work, detectors are derived that exploit known properties of the second-order moments of the signal. In particular, known structures of the signal covariance are exploited to circumvent the problem of unknown parameters, such as noise and signal powers or channel coefficients.The dissertation is comprised of six papers, all in different ways related to spectrum sensing based on second-order statistics. In the first paper, we considerspectrum sensing of orthogonal frequency-division multiplexed (OFDM) signals in an additive white Gaussian noise channel. For the case of completely known noise and signal powers, we set up a vector-matrix model for an OFDM signal with a cyclic prefix and derive the optimal Neyman-Pearson detector from first principles. For the case of completely unknown noise and signal powers, we derive a generalized likelihood ratio test (GLRT) based on empirical second-order statistics of the received data. The proposed GLRT detector exploits the non-stationary correlation structure of the OFDM signal and does not require any knowledge of the noise or signal powers.In the second paper, we create a unified framework for spectrum sensing of signals which have covariance matrices with known eigenvalue multiplicities. We derive the GLRT for this problem, with arbitrary eigenvalue multiplicities under both hypotheses. We also show a number of applications to spectrum sensing for cognitive radio.The general result of the second paper is used as a building block, in the third and fourth papers, for spectrum sensing of second-order cyclostationary signals received at multiple antennas and orthogonal space-time block coded (OSTBC) signals respectively. The proposed detector of the third paper exploits both the spatial and the temporal correlation of the received signal, from knowledge of the fundamental period of the cyclostationary signal and the eigenvalue multiplicities of the temporal covariance matrix.In the fourth paper, we consider spectrum sensing of signals encoded with an OSTBC. We show how knowledge of the eigenvalue multiplicities of the covariance matrix are inherent owing to the OSTBC, and propose an algorithm that exploits that knowledge for detection. We also derive theoretical bounds on the performance of the proposed detector. In addition, we show that the proposed detector is robust to a carrier frequency offset, and propose another detector that deals with timing synchronization using the detector for the synchronized case as a building block.A slightly different approach to covariance matrix estmation is taken in the fifth paper. We consider spectrum sensing of Gaussian signals with structured covariance matrices, and propose to estimate the unknown parameters of the covariance matrices using covariance matching estimation techniques (COMET). We also derive the optimal detector based on a Gaussian approximation of the sample covariance matrix, and show that this is closely connected to COMET.The last paper deals with the problem of discriminating samples that containonly noise from samples that contain a signal embedded in noise, when the variance of the noise is unknown. We derive the optimal soft decision detector using a Bayesian approach. The complexity of this optimal detector grows exponentially with the number of observations and as a remedy, we propose a number of approximations to it. The problem under study is a fundamental one andit has applications in signal denoising, anomaly detection, and spectrum sensing for cognitive radio.
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| 8. |
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| 9. |
- Cirkic, Mirsad, et al.
(författare)
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Approximating the LLR Distribution for a Class of Soft-Output MIMO Detectors
- 2012
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Ingår i: IEEE Transactions on Signal Processing. - : Institute of Electrical and Electronics Engineers (IEEE). - 1053-587X .- 1941-0476. ; 60:12, s. 6421-6434
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Tidskriftsartikel (refereegranskat)abstract
- We present approximations of the LLR distribution for a class of fixed-complexity soft-output MIMO detectors, such as the optimal soft detector and the soft-output via partial marginalization detector. More specifically, in a MIMO AWGN setting, we approximate the LLR distribution conditioned on the transmitted signal and the channel matrix with a Gaussian mixture model (GMM). Our main results consist of an analytical expression of the GMM model (including the number of modes and their corresponding parameters) and a proof that, in the limit of high SNR, this LLR distribution converges in probability towards a unique Gaussian distribution.
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| 10. |
- Čirkić, Mirsad, 1984-, et al.
(författare)
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Gaussian Approximation of the LLR Distribution for the ML and Partial Marginalization MIMO detectors
- 2011
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Ingår i: Proceedings of the IEEE International Conference on Acoustics, Speech and SignalProcessing (ICASSP). - : IEEE conference proceedings. - 9781457705373 ; , s. 3232-3235
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Konferensbidrag (refereegranskat)abstract
- We derive a Gaussian approximation of the LLR distribution conditioned on the transmitted signal and the channel matrix for the soft-output via partial marginalization MIMO detector. This detector performs exact ML as a special case. Our main results consist of discussing the operational meaning of this approximation and a proof that, in the limit of high SNR, the LLR distribution of interest converges in probability towards a Gaussian distribution.
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