| 1. |
- Carlsson, Anders, et al.
(författare)
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Plasma proteome profiling reveals biomarker patterns associated with prognosis and therapy selection in glioblastoma multiforme patients
- 2010
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Ingår i: Proteomics Clinical Applications. - : Wiley. - 1862-8354 .- 1862-8346. ; 4:6-7, s. 591-602
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Glioblastoma multiforme (GBM) is a frequent and aggressive type of primary brain tumor with a heterogeneous origin. GBM is highly therapy resistant and carries a dismal prognosis for the patient. The purpose of this discovery study was to define candidate plasma biomarker signatures for improved classification and novel means for selecting patients for refined individualized therapy. Experimental design: Here, we have for the first time investigated the applicability of large-scale recombinant antibody-based microarrays, targeting mainly immunoregulatory analytes, for sensitive and selective plasma protein profiling of GBM patients undergoing immunotherapy with autologous IFN-gamma transfected glioma cells Results: This proof-of-concept study showed that candidate plasma protein signatures associated with GBM were outlined that could be used for GBM classification, monitoring the effects of the immunotherapy as well as for stratifying patients according to the beneficial effect of the adopted immunotherapy Further, central key cytokines that could be utilized for optimization and/or refinement of the immunotherapeutic regime were indicated. Conclusions and clinical relevance: Candidate plasma proteins signatures associated with GBM was outlined, that could be used for GBM classification and for pre-operatively stratifying patients according to the beneficial effect of the adopted immunotherapy.
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| 2. |
- Carlsson, Anders, et al.
(författare)
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Serum protein profiling of systemic lupus erythematosus and systemic sclerosis using recombinant antibody microarrays.
- 2011
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Ingår i: Molecular & Cellular Proteomics. - 1535-9484. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are two severe autoimmune connective tissue diseases. The fundamental knowledge about their aetiology is limited and the conditions display complex pathogenesis, multifaceted presentations, and unpredictable courses. Despite significant efforts, the lack of fully validated biomarkers enabling diagnosis, classification, and monitoring of disease activity represents significant unmet clinical needs. In this discovery study, we have for the first time used recombinant antibody microarrays for miniaturized, multiplexed serum protein profiling of SLE and SSc, targeting mainly immunoregulatory proteins. The data showed that several candidate SLE-associated multiplexed serum biomarker signatures were delineated, reflecting disease (diagnosis), disease severity (phenotypic subsets) and disease activity. Selected differentially expressed markers were validated using orthogonal assays and a second, independent patient cohort. Further, biomarker signatures differentiating SLE versus SSc were demonstrated, and the observed differences increased with severity of SLE. In contrast, the data showed that the serum profiles of SSc versus healthy controls were more similar. Hence, we have shown that affinity proteomics could be used to de-convolute crude, non-fractionated serum proteomes, extracting molecular portraits of SLE and SSc, further enhancing our fundamental understanding of these complex autoimmune conditions.
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| 3. |
- Wingren, Carl Johan, et al.
(författare)
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Acculturation and celiac disease risk in second-generation immigrants: a nationwide cohort study in Sweden.
- 2012
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 47:10, s. 1174-1180
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The burden of celiac disease (CD) is increasingly recognized as a global problem. However, whether this situation depends on genetics or environmental factors is uncertain. The authors examined these aspects in Sweden, a country in which the risk of CD is generally considered to be high. If environmental factors are relevant, CD risk in second-generation immigrant children should be related to maternal length of stay in Sweden before delivery. Material and methods: Linking the Swedish Medical Birth Registry to other national registries, the authors investigated all singleton children (n = 792,401) born in Sweden between 1987 and 1993. They studied the risk of CD in children before age 6 as a function of the mother's geographical region of birth and length of stay in Sweden before delivery using Cox regression models. Results: In children whose mothers immigrated to Sweden from a country outside of Europe, a maternal length of stay in Sweden of more than 5 years increased the hazard ratio (HR) of CD (1.73, 95% confidence interval (CI) 1.06-2.81). The authors observed a similar result among children born to mothers from a Nordic country outside of Sweden (HR 1.57, 95% CI 0.89-2.75), but a non-conclusive protective effect was observed in second-generation immigrant children from a non-Nordic European country (HR 0.65, 95% CI 0.39-1.09). Conclusions: The risk of CD among second-generation immigrants seems to be conditioned by maternal length of stay in Sweden before delivery, suggesting that environmental factors contribute to the variation in CD risk observed across populations.
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| 4. |
- Wingren, Carl Johan, et al.
(författare)
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Coeliac disease in children: a social epidemiological study in Sweden
- 2012
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Ingår i: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 101:2, s. 185-191
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Little is known on the possible existence of socioeconomic and geographical differences in early coeliac disease (CD) risk. Therefore, we investigated these aspects in children before age two. Methods: Linking the Swedish Medical Birth Registry to several other national registries, we identified all singletons born in Sweden from 1987 to 1993 (n = 792 401) and followed them until 2 years of age to identify cases of CD. Applying multilevel logistic regression analysis, we investigated the association between socioeconomic position (SEP) and CD in children and also whether a possible geographical variation in CD risk was explained by individual characteristics. Results: Low SEP was associated with CD in boys OR 1.37 (95% CI 1.03-1.82), but not in girls OR 0.87 (95% CI 0.68-1.12). We found a considerable geographical variation in disease risk (i.e. intra-municipality correlation approximate to 10%) that was not explained by individual characteristics. Conclusions: Low SEP is associated with CD in boys but not in girls. Also, CD appears to be conditioned by geographical area of residence. While our study represents an innovative contribution to the epidemiology of CD in children, the reasons for the observed geographical and socioeconomic differences could be speculated but are still unknown.
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| 5. |
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| 6. |
- Wingren, Carl Johan, et al.
(författare)
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Congenital Anomalies and Childhood Celiac Disease: A Swedish Register-based Study.
- 2012
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Ingår i: Journal of Pediatric Gastroenterology and Nutrition - Jpgn. - 1536-4801. ; 55:6, s. 736-739
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Tidskriftsartikel (refereegranskat)abstract
- Previously, chromosomal anomalies, and to a lesser extent, other congenital anomalies have been associated with an increased risk of celiac disease (CD). We investigated these associations using a systematic approach. We identified all singleton children (792,401) born in Sweden between 1987 and 1993, and obtained cases of CD using the Swedish National Inpatient Registry. We applied COX regression models as well as sibling designs to study the association between congenital anomalies and childhood CD. We observed that anomalies of either face, neck, ear, heart, digestive tract or of chromosomes were associated with CD.
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| 7. |
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| 8. |
- Wingren, Carl Johan, et al.
(författare)
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Revisiting the risk of celiac disease in children born small for gestational age: A sibling design perspective.
- 2012
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 47:6, s. 632-639
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Tidskriftsartikel (refereegranskat)abstract
- Objective: An association between small for gestational age (SGA) and risk for celiac disease (CD) in childhood has previously been reported. However, this association may reflect residual confounding by genetic or environmental factors. For example, presence of subclinical CD in the mother might be a common cause of both SGA and CD in the offspring. We investigate whether SGA is causally associated with CD before age six years by applying both conventional population-based regression models and sibling analysis that investigates the association in siblings discordant for SGA. Material and methods: Using the Swedish Medical Birth Registry, we identified all singleton children born in Sweden during 1987-1993 (792,401). Of these we included 681,954 children in the study and identified 2641 cases of CD using the Swedish National In-Hospital Registry. We applied both conventional Cox regression analysis and a quasi-experimental sibling design that to some extent simulates a counterfactual situation of exposure, reducing possible confounding effects of genetic and shared environmental factors. Results: We identified an increased risk of CD in both boys (hazard ratio (HR) 1.70, 95% confidence interval (CI) 1.25-2.32) and girls (HR 1.30, 95% CI 0.99-1.70) using conventional Cox regression models. Using sibling analysis, the association between SGA and CD was confirmed in boys (HR 4.23, 95% CI 1.19-15.04) but not in girls (HR 1.00, 95% CI 0.45-2.20). Conclusions: Our results support a causal association between SGA and CD risk in boys but not in girls, although the mechanisms underlying this difference are still unclear.
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| 9. |
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| 10. |
- Wingren, Carl Johan, et al.
(författare)
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Sex differences in coeliac disease risk: A Swedish sibling design study.
- 2012
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Ingår i: Digestive and Liver Disease. - : Elsevier BV. - 1590-8658. ; 44:11, s. 909-913
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: For unknown reasons girls are at an increased risk of coeliac disease compared to boys. However, the observed association might be confounded, since maternal coeliac disease is associated with both an increased risk of the disease in first-degree relatives as well as an increased ratio of girls to boys in offspring. AIMS: We investigate the effect of sex on the risk of coeliac disease before the age of two years using sibling design. METHODS: We identified all singleton children (n=792,401) born between 1987 and 1993 in Sweden using the Swedish Medical Birth Registry. Coeliac disease cases (2264) were identified using the Swedish National Inpatient Registry. We applied both conventional population-based Cox regression models and sibling designs modelling the association in sex discordant siblings. RESULTS: We observed a conclusively increased risk of coeliac disease in girls compared to boys, using both sibling design (hazard ratio 1.67, 95% confidence interval 1.44-1.93) and conventional Cox regression analysis (hazard ratio 1.75, 95% confidence interval 1.61-1.91) that could not be explained by perinatal factors previously associated with the disease. CONCLUSIONS: We confirm that female sex is causally associated with childhood coeliac disease, but the reasons remains unknown.
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