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- Sandström, Olof, et al.
(författare)
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Transglutaminase IgA antibodies in a celiac disease mass screening and the role of HLA-DQ genotyping and endomysial antibodies in a sequential testing
- 2013
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Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - : Lippincott Williams & Wilkins. - 0277-2116 .- 1536-4801. ; 57:4, s. 472-476
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to evaluate hypothetical screening strategies in a Swedish celiac disease (CD) mass screening.Methods: Of 10,041 Swedish sixth graders born in 1993 invited to a population-based CD mass screening, 7208 participated. Anti-tissue transglutaminase (tTG) immunoglobulin (Ig) A were analyzed in all children and total serum IgA (s-IgA) in 7161 children. Additional analyses of tTG-IgG, endomysial antibodies (EMA) IgA and IgG, and human leukocyte antigen (HLA) alleles were performed according to a standardized protocol. Children with elevated levels of serological markers were recommended to undergo a small intestinal biopsy to verify diagnosis, and 153 children with CD were thus identified. Sensitivity, specificity, positive predictive values (PPVs) and negative predictive values (NPVs) were calculated and receiver operating characteristic curves were plotted.Results: By lowering the cutoff for tTG-IgA, 17 additional cases of CD were identified at the cost of 32 biopsies. All children with tTG-IgA >50 U/mL (10 times the recommended upper limit of normal) had gluten enteropathy. Area under the receiver operating characteristic curve for tTG-IgA was 0.988. All cases carried HLA-DQ2 or HLA-DQ8, as did 53% of the controls. For different hypothetical screening strategies, sensitivity, specificity, PPV, and NPV ranged between 87.6% and 100%, 99.5% and 99.9%, 79.7% and 89.7%, and 99.7% and 100%, respectively. Efforts to increase sensitivity by lowering tTG-IgA cutoff would result in increased number of small intestinal biopsies and lower PPV. Sequential testing for both EMA and HLA-DQ genotyping would reduce the number of negative small intestinal biopsies.Conclusions: tTG-IgA is a robust marker when used in CD mass screening and its performance can be enhanced by sequential testing for EMA or HLA-DQ genotyping.
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| 3. |
- Myhrinder, Anna Lanemo, 1975-, et al.
(författare)
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Molecular characterization of neoplastic and normal "sister" lymphoblastoid B-cell lines from chronic lymphocytic leukemia
- 2013
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 54:8, s. 1769-1779
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Tidskriftsartikel (refereegranskat)abstract
- Chronic lymphocytic leukemia (CLL) B-cells resemble self-renewing CD5 + B-cells carrying auto/xeno-antigen-reactive B-cell receptors (BCRs) and multiple innate pattern-recognition receptors, such as Toll-like receptors and scavenger receptors. Integration of signals from BCRs with multiple surface membrane receptors determines whether the cells will be proliferating, anergic or apoptotic. To better understand the role of antigen in leukemogenesis, CLL cell lines producing monoclonal antibodies (mAbs) will facilitate structural analysis of antigens and supply DNA for genetic studies. We present here a comprehensive genotypic and phenotypic characterization of available CLL and normal B-cell-derived lymphoblastoid cell lines (LCLs) from the same individuals (n = 17). Authenticity and verification studies of CLL-patient origin were done by IGHV sequencing, fluorescence in situ hybridization (FISH) and DNA/short tandem repeat (STR) fingerprinting. Innate B-cell features, i.e. natural Ab production and CD5 receptors, were present in most CLL cell lines, but in none of the normal LCLs. This panel of immortalized CLL-derived cell lines is a valuable reference representing a renewable source of authentic Abs and DNA.
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| 4. |
- Nordyke, Katrina, 1975-, et al.
(författare)
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Internalizing the threat of risk : a qualitative study about adolescents' experience living with screening-detected celiac disease 5 years after diagnosis
- 2014
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Ingår i: Health and Quality of Life Outcomes. - : BioMed Central. - 1477-7525 .- 1477-7525. ; 12
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Mass screening could identify those with unrecognized celiac disease (CD), but the experience of being detected through screening and living with screening-detected CD should be explored before considering this as acceptable intervention. For this study we invited screening-detected adolescents to describe their experience living with screening-detected CD five years after diagnosis with the aim to explore how their perceptions, practices, and beliefs evolved.METHODS: Adolescents who were diagnosed through a population-based CD screening were invited to write narratives after being diagnosed. Of 153 adolescents who were eventually diagnosed through the screening, 91 wrote narratives one year after diagnosis and 72 five years after diagnosis. A qualitative content analysis resulted in a theme and categories that describe the experience living with screening-detected CD five years after diagnosis.RESULTS: The overall theme - "Internalizing the threat of risk" - illustrates that being detected through screening and the internalized threat of future health complications have impacted how these adolescents felt about the diagnosis, coped with the gluten-free diet (GFD), and thought about CD screening. This theme is supported by four categories: maintaining an imposed disease identity describes how they continued to define their diagnosis in relation to the screening. They also expressed moving from forced food changes to adapted diet routines by describing habits, routines, coping strategies, and the financial burden of the GFD. They had enduring beliefs of being spared negative consequences, however, even after five years, some doubted they had CD and worried that being detected and eating a GFD might not be beneficial, i.e. "continuing to fear it is "all in vain".CONCLUSIONS: There was maintenance and evolution in the perceptions, practices, and beliefs of the adolescents after five years. Some have adjusted to the disease and adapted new habits and coping strategies to deal with the GFD, while others still doubt they have CD or that being detected was beneficial. The transition to adapting to the disease and GFD is ongoing, illustrating the importance of providing ongoing support for those with screening-detected CD as they adjust to this chronic disease and the GFD.
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| 5. |
- Rosén, Anna, 1975-, et al.
(författare)
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Balancing health benefits and social sacrifices : a qualitative study of how screening-detected celiac disease impacts adolescents' quality of life
- 2011
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Ingår i: BMC Pediatrics. - : BioMed Central. - 1471-2431 .- 1471-2431. ; 11, s. 32-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCeliac disease often goes undiagnosed. Mass screening might be an option to reduce the public health burden of untreated celiac disease. However, mass screening is still controversial since it is uncertain whether the benefits of early detection outweigh the possible negative consequences. Before implementation of screening programs, the experiences of those being identified as cases should be considered. The aim of our study was to explore how screening-detected celiac disease impacts adolescents' quality of life, as perceived by themselves and their parents.MethodsAll adolescents (n = 145) with screening-detected celiac disease found in a Swedish screening study, and their parents, were invited to share their experiences in a qualitative follow-up study. In total, we have information on 117 (81%) of the adolescents, either from the adolescents themselves (n = 101) and/or from their parent/s (n = 125). Written narratives were submitted by 91 adolescents and 105 parents. In addition, 14 focus group discussions involving 31 adolescents and 43 parents were conducted. Data was transcribed verbatim and analyzed based on a Grounded Theory framework.ResultsThe screening-detected celiac disease diagnosis had varying impact on quality of life that related both to changes in perceived health and to the adolescents' experiences of living with celiac disease in terms of social sacrifices. Changes in perceived health varied from "healthy as anyone else with no positive change" to "something was wrong and then changed to the better", whereas experiences of living with celiac disease ranged from "not a big deal" to "treatment not worth the price". Perceptions about living with celiac disease and related coping strategies were influenced by contextual factors, such as perceived support from significant others and availability of gluten-free products, and were developed without a direct relation to experiencing changes in perceived health.ConclusionsScreening-detected celiac disease has varying impact on adolescents' quality of life, where their perceived change in health has to be balanced against the social sacrifices the diagnosis may cause. This needs to be taken into account in any future suggestion of celiac disease mass screening and in the management of these patients.
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| 6. |
- Rosén, Anna, 1975-
(författare)
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Mass screening for celiac disease in 12-year-olds : Finding them and then what?
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Mass screening for celiac disease (CD) as a public health intervention is controversial. Before implementation, a suitable screening strategy should be outlined, and the acceptability of the screening scrutinized. Also, the benefits of early detection and possible negative consequences should be explored and compared. The overall aim of this thesis was to evaluate different strategies for finding 12-year-olds with undiagnosed CD in the general population, and to explore the experiences of those receiving the diagnosis in a mass screening.Methods A school-based CD screening of 12-year-olds was conducted in five study sites across Sweden. Out of 10041 children who were invited, 7208 had a blood sample analyzed for CD-marker tissue transglutaminase of isotype IgA (tTG-IgA) and 7161 for total serum IgA (s-IgA). If the s-IgA value was low, tTG-IgG was also measured. Additional analysis of endomysial antibodies (EMA) was performed if borderline values of tTG were found. In total, 192 had elevated CD-markers, 184 underwent a small intestinal biopsy and 153 eventually had CD diagnosed. Before receiving knowledge about their CD status, children and their parents filled in questionnaires regarding symptoms and CD-associated conditions. Questionnaires were returned by 7054 children (98%) and 6294 parents (88%). Later, all adolescents who had been diagnosed with CD more than one year ago (n=145), and their parents, were invited to a mixed-method follow-up study in which they shared their experiences in questionnaires, written narratives and focus group discussions. In total, we have information on 117 (81%) of these adolescents, either from the adolescents themselves (n=101) and/or from their parent/s (n=125). Data were analyzed using a combination of descriptive and analytical quantitative and qualitative methodologies.Results We found that information on symptoms and CD-associated conditions were poor predictors for finding undiagnosed CD in the study population. Questionnaire-based case-finding by asking for CD-associated symptoms and conditions would have identified 52 cases (38% of all cases) at a cost of blood-sampling 2282 children (37% of the study population). The tTG-IgA test had an excellent diagnostic accuracy with the area under the receiver operating characteristic curve of 0.988. If using the recommended cut-off for tTG-IgA (>5 U/mL) 151 had fulfilled biopsy criteria and 134 CD cases had been identified. The strategy of lowering the cut-off to tTG-IgA>4 U/mL, and adding the EMA analysis in those with tTG-IgA between 2-4 U/mL, identified another 17 cases (a 12% increase) at the cost of performing 32 additional biopsies. Measuring total s-IgA in 7161 children discovered only two additional cases at the cost of performing 5 additional biopsies. The positive predictive value of our screening strategy was 80%. Results from the follow-up study of the screening-detected CD cases illustrated that 54% reported health improvement after initiated treatment, but also that these health benefits had to be balanced against social sacrifices. We also found that although the screening-detected diagnosis was met with surprise and anxiety, the adolescents and their parents were grateful for being made aware of the diagnosis. A majority of parents (92%) welcomed a future screening, but both adolescents and parents suggested that it should be conducted earlier in life.Conclusion Obtaining information on symptoms and CD-associated conditions was not a useful step in finding undiagnosed CD cases in a general population. The serological marker tTG-IgA, however, had excellent diagnostic accuracy also when lowering the cut-off. The diagnosis had varying impact on adolescents’ quality of life, and their perceived change in health had to be balanced against the social sacrifices resulting from the diagnosis. Overall, CD mass screening seemed acceptable to most of those who were diagnosed and their parents.
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